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Table of contents

List of Investigators………………………………………………………………………………..2 Supplemental Methods………………………………………………………………………….....3 Supplemental Figures……………………………………………………………………………...4 Supplemental Tables………………………………………………………………………………7

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List of Investigators

Steering Committee: Keith Sullivan, M.D. (Principal Investigator and NIH Contract Holder), Daniel Furst, M.D. and Peter McSweeney, M.D. (Protocol Co-chairs), Ellen Goldmuntz, M.D., Ph.D. (Medical Monitor), Lynette Keyes-Elstein, Dr. P.H. (Senior Statistical Scientist), Leslie Crofford, M.D., Richard Nash M.D., Maureen Mayes M.D.

DAIT, NIAID Program: Ellen Goldmuntz, M.D., Ph.D. (Medical Officer)

Statistical and Clinical Coordinating Center: Lynette Keyes-Elstein, Dr. P.H. (SACCC Principal Investigator), Ashley Pinckney, MS (Statistician)

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Supplemental Methods

Study participants SCOT trial participants fulfilled the 1980 American College of Rheumatology classification criteria for SSc in addition to the following criteria: age 18-69 years, disease onset within 5 years (from first non-Raynaud’s symptom), diffuse cutaneous involvement, internal organ involvement of either pulmonary disease (DLco or FVC <70%) or prior scleroderma renal crisis. More detailed inclusion criteria are provided in the primary clinical manuscript (Sullivan et al 2018). Healthy controls were enrolled in the UT Houston Divisional Repository, did not have a systemic autoimmune disease, and were not first-degree relatives of an individual with SSc.

Collection of Peripheral Blood Mononuclear Cells Whole blood samples were collected in Tempus tubes (Applied Biosystems, Foster City, California, USA) and stored at −80°C. RNA was extracted at Fisher according to the protocol attached at the end of the supplementary materials. RNA quality was assessed using Bioanalyzer (Agilent Genomics, Santa Clara, California, USA) and those with RNA integrity numbers >7 were examined.

Gene Expression Data Preprocessing RNA was purified from baseline and longitudinal PBMC samples collected from SCOT trial participants. cRNA was hybridized to Agilent (Santa Clara, CA, USA) 8x60k SurePrint G3 Human Expression Microarrays. Agilent Feature Extraction Image Analysis Software (Version 10.7.3) was used to extract data from raw microarray image files. Microarray data were log2- lowess normalized and filtered for probes with intensity ≥1.5-fold over local background in Cy3 or Cy5 channels. Expression values were multiplied by −1 to convert them to log2(Cy3/Cy5) ratios. Probes were filtered to include only those with <20% missing values across samples. For downstream statistical analyses, the missing probe values were imputed using k-Nearest- Neighbors imputation function in GenePattern. Importantly, no subjects or timepoints were imputed. Because multiple probes are used to measure the expression of a single gene, probe values were next collapsed to unique , selecting the maximum value, using GenePattern. The CHIP file used for collapsing probes to genes is available with the gene expression data (GSE134310). Gene expression data were median-centered across genes using Cluster 3.0, and visualized using Java TreeView.

Weighted Gene Co-expression Network Analyses We used weighted gene co-expression network analysis (WGCNA) to identify modules of genes by constructing a signed network using default power of 12. WGCNA is a powerful, unsupervised clustering technique to identify groups of co-expressed genes. We identified a total of 58 modules and calculated the correlation of the eigenvalues for each module to the intrinsic subset labels generated by the machine learning classifier (Fig. S1). A module that is significantly positively

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correlated to an intrinsic subset represents a group of genes that is upregulated in that intrinsic subset compared to the other intrinsic subsets. We selected the top positively correlated module to each intrinsic subset for further analysis. To show that the module is significantly upregulated in the intrinsic subset, we used pairwise Wilcoxon Rank Sum tests to compare the eigenvalues between the intrinsic subsets. For each module associated with an intrinsic subset, we used the list of genes for that module and performed analyses (g:Profiler) to identify the molecular processes upregulated in that intrinsic subset. GO terms with p<0.05 corrected for multiple testing via default g:SCS method were treated as significant and reported in Figure 1.

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Supplemental Figures

Supplemental Figure S1. PCA of all gene expression data colored by collection site. Principle components were calculated using all gene expression data. PC1 captured 26.94% of the variation in the data and PC2 captured 9.63%. Colors are intermixed, indicating that there is no strong collection site bias in the gene expression data. Each point on the graph represents a single gene expression sample and is colored according to collection site. Some patients may have received treatment at multiple sites, but we did not have access to this information.

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Supplementary Figure S2. Differential Gene Expression Analysis between Intrinsic Subsets. Here, we performed a differential gene expression analysis using unpaired t-test in SAM (Statistical Analysis of Microarrays). We identified genes differentially expressed at FDR 0% between healthy controls and each of the intrinsic subsets: fibroproliferative (A), inflammatory (B), and normal-like (C). There were 814 up-regulated genes and 2898 down-regulated genes in the fibroproliferative subset compared to controls. There were 884 up-regulated genes and 1278 down-regulated genes in the inflammatory subset compared to controls. There were 33 up- regulated genes and 329 down-regulated genes in the normal-like subset compared to controls. The descriptions on the right-hand side of the heatmap correspond to significant biological processes identified by g:Profiler (GO terms with p<0.05 corrected for multiple testing via default g:SCS ). The full gene lists are included as Supplementary Table S7.

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Supplemental Figure S3. Gene modules identified with WGCNA from SCOT baseline samples. Heatmap displays the Spearman correlation of module eigenvalues with intrinsic subsets.

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Supplemental Figure S4. Event-free survival (EFS) by intrinsic subset and treatment arm. Comparison between the intrinsic subsets in terms of EFS within transplantation (A) and cyclophosphamide (B) treatment arms.

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Supplemental Figure S5. General gene expression trends in SCOT treatment arms. Principal Component Analysis was performed on all genes between the paired samples from patients at baseline and 48/54 months in cyclophosphamide (A) and transplantation (B) arms, respectively. Each point is a sample, each color represents a timepoint (pre/post-treatment), and ellipses represent 95% confidence intervals. There is no difference between pre- and post-treatment in the cyclophosphamide arm. However, in the transplantation arm, there is an evident shift between the pre- and post-treatment samples. This indicates that there is major gene expression variation sustained long-term following stem cell transplant.

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Supplemental Tables Supplemental Table S1. Overview of SCOT participant samples used in this study. Patient 8 14 20/26 38 44/48/54 Treatment Baseline PP ID months months months months months Arm 2 ✔ ✔ ✔ ✔ ✔ ✔ Yes HSCT 4 ✔ ✔ ✔ Yes CYC 5 ✔ Yes CYC 6 ✔ Yes HSCT 7 ✔ Yes CYC 8 ✔ Yes CYC 9 ✔ ✔ ✔ ✔ ✔ ✔ Yes CYC 10 ✔ ✔ ✔ ✔ ✔ ✔ Yes CYC 11 ✔ Yes HSCT 12 ✔ ✔ ✔ Yes CYC 13 ✔ ✔ ✔ ✔ ✔ ✔ Yes HSCT 14 ✔ ✔ ✔ ✔ ✔ ✔ Yes CYC 15 ✔ ✔ ✔ ✔ ✔ ✔ Yes HSCT 17 ✔ No CYC 18 ✔ Yes CYC 19 ✔ ✔ ✔ ✔ ✔ ✔ Yes CYC 20 ✔ ✔ ✔ Yes HSCT 21 ✔ Yes HSCT 23 ✔ ✔ ✔ ✔ ✔ ✔ Yes CYC 24 ✔ ✔ ✔ ✔ ✔ ✔ Yes HSCT 25 ✔ ✔ ✔ ✔ ✔ Yes CYC 26 ✔ Yes CYC 27 ✔ Yes HSCT 28 ✔ ✔ ✔ ✔ ✔ ✔ Yes HSCT 29 ✔ ✔ ✔ Yes CYC 30 ✔ ✔ ✔ ✔ Yes CYC 31 ✔ ✔ ✔ Yes CYC 32 ✔ ✔ ✔ ✔ Yes HSCT 33 ✔ Yes HSCT 34 ✔ Yes HSCT 35 ✔ ✔ ✔ ✔ ✔ ✔ Yes CYC 36 ✔ No CYC 37 ✔ ✔ ✔ Yes HSCT 38 ✔ Yes CYC 39 ✔ ✔ ✔ Yes CYC 41 ✔ ✔ ✔ ✔ ✔ ✔ Yes CYC 42 ✔ Yes HSCT 43 ✔ ✔ ✔ ✔ ✔ Yes CYC 44 ✔ ✔ ✔ ✔ ✔ ✔ Yes HSCT 45 ✔ ✔ ✔ ✔ ✔ ✔ Yes HSCT 47 ✔ ✔ ✔ ✔ ✔ Yes CYC 48 ✔ ✔ ✔ ✔ ✔ ✔ Yes HSCT 50 ✔ Yes CYC 51 ✔ ✔ Yes HSCT 52 ✔ ✔ ✔ Yes HSCT 53 ✔ ✔ ✔ ✔ Yes HSCT 54 ✔ No HSCT 55 ✔ ✔ ✔ ✔ ✔ ✔ Yes HSCT 56 ✔ ✔ ✔ ✔ ✔ Yes CYC 57 ✔ Yes HSCT 58 ✔ ✔ ✔ Yes HSCT 59 ✔ ✔ ✔ ✔ ✔ ✔ Yes HSCT 60 ✔ ✔ ✔ ✔ ✔ ✔ Yes HSCT 61 ✔ Yes CYC 62 ✔ ✔ ✔ ✔ Yes CYC 63 ✔ ✔ ✔ ✔ ✔ Yes CYC 64 ✔ Yes CYC 65 ✔ ✔ ✔ ✔ ✔ ✔ Yes HSCT 66 ✔ No CYC 67 ✔ ✔ ✔ ✔ ✔ Yes CYC 68 ✔ Yes CYC 70 ✔ ✔ ✔ Yes CYC 71 ✔ Yes HSCT

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72 ✔ Yes HSCT 73 ✔ ✔ ✔ ✔ ✔ ✔ Yes CYC 74 ✔ ✔ ✔ ✔ ✔ ✔ Yes HSCT 75 ✔ ✔ ✔ ✔ ✔ Yes CYC

Supplemental Table S2. Extended version of Table 1 from the main manuscript. Characteristic Transplant Cyclophosphamide P-value (N=30) (N=33) Age (Years) - Mean (SD+) 43.8 (10.10) 46.1 (10.66) 0.379

Sex Male – no. (%) 15 (50.0) 10 (30.3) 0.129 Female – no. (%) 15 (50.0) 23 (69.7)

Race White – no. (%) 23 (76.7) 25 (75.8) 0.805 Black or African American – no. (%) 2 (6.7) 4 (12.1) Asian – no. (%) 2 (6.7) 1 (3.0) Native Hawaiian/Other Pacific Islander – 0 0 no. (%) American Indian or Alaska Native – no. (%) 0 0 Multiple Races – no. (%) 2 (6.7) 3 (9.1) Other – no. (%) 0 0 Unknown – no. (%) 1 (3.3) 0

Ethnicity Hispanic or Latino – no. (%) 3 (10.0) 4 (12.1) >0.999 Not Hispanic or Latino – no. (%) 26 (86.7) 29 (87.9)

Smoking History Current – no. (%) 1 (3.3) 2 (6.1) 0.41 Ever – no. (%) 9 (30.0) 5 (15.2) Never – no. (%) 20 (66.7) 26 (78.8)

Disease Duration - Mean (SD) 24.9 (12.7) 30.8 (16.4) 0.117

Lung Involvement Yes – no. (%) 30 (100.0) 32 (97.0) >0.999 No – no. (%) 0 1 (3.0)

Kidney Involvement Yes – no. (%) 0 3 (9.1) 0.24 No – no. (%) 30 (100.0) 30 (90.9)

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Characteristic Transplant Cyclophosphamide P-value

Gastric Antral Vascular Ectasia [1] Yes – no. (%) 8 (26.7) 5 (15.2) 0.353 No – no. (%) 22 (73.3) 28 (84.8)

Oral Aperture (mm) - Mean (SD) 49.5 (9.1) 43.5 (10.6) 0.019

Modified Rodnan Skin Score (MRSS) - 27.5 (7.7) 30.4 (10.7) 0.225 Mean (SD)

Disease-modifying Anti-rheumatic Drug (DMARD) Use Within 6 Months of Randomization Yes – no. (%) 23 (76.7) 21 (63.6) 0.287 No – no. (%) 7 (23.3) 12 (36.4)

DMARD Use Ever Yes – no. (%) 24 (80.0) 27 (81.8) >0.999 No – no. (%) 6 (20.0) 6 (18.2)

Autoantibodies Anti-SCL 70 Positive – no. (%) 11 (36.7) 16 (48.5) 0.446 Negative – no. (%) 18 (60.0) 17 (51.5) Not Done – no. (%) 1 (3.3) 0

Anti-nuclear Antibody (ANA) Positive – no. (%) 27 (90.0) 28 (84.8) 0.835 Negative – no. (%) 2 (6.7) 4 (12.1) Not Done – no. (%) 1 (3.3) 1 (3.0)

Anti-RNA Pol III Positive – no. (%) 1 (3.3) 5 (15.2) 0.358 Negative – no. (%) 11 (36.7) 10 (30.3) Not Done – no. (%) 18 (60.0) 18 (54.5)

Scleroderma Health Assessment 1.1 (0.6) 1.3 (0.86) 0.209 Questionnaire (SHAQ) - Mean (SD)

FVC (% Predicted) - Mean (SD) 76.2 (13.4) 73.64 (17.9) 0.525

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Characteristic Transplant Cyclophosphamide P-value Hb Adjusted DLCO (% Predicted) [2] – 54.13 (6.7) 51.75 (7.9) 0.207 Mean (SD)

Estimated Peak Systolic Pulmonary 27.8 (8.1) 31.3 (6.0) 0.127 Artery Pressure - Mean (SD)

CPK (U/L) - Mean (SD) 126.8 (107.6) 194.7 (231.8) 0.175

ESR (mm/hr) - Mean (SD) 30.7 (27.2) 29.1 (19.5) 0.799

Creatinine (mg/dL) - Mean (SD) 0.7 (0.1) 0.7 (0.3) 0.914

Creatinine Clearance (mL/min) – 126.9 (38.3) 128.6 (54.4) 0.885 Mean (SD)

Hemoglobin (g/dL) - Mean (SD) 12.6 (1.1) 12.2 (1.4) 0.227

3 Platelet Count (10 /uL) - Mean (SD) 302.2 (87.2) 312.1 (100.8) 0.683

Weight (kg) - Mean (SD) 72.4 (15.7) 73.0 (17.2) 0.874

BMI - Mean (SD) 24.6 (4.1) 26.0 (6.1) 0.287

History of Other Autoimmune Diseases Yes – no. (%) 29 (96.7) 29 (87.9) 0.357 No – no. (%) 1 (3.3) 4 (12.1)

History of Raynaud’s Phenomenon Yes – no. (%) 30 (100.0) 33 (100.0) No – no. (%) 0 0

SF36 Physical Function Component Score 30.7 (9.5) 30.1 (9.1) 0.799 – Mean (SD)

SF36 Mental Component Score 44.3 (10.6) 45.0 (10.5) 0.801 – Mean (SD)

[1] Gastric Antral Vascular Ectasia =GAVE [2] Hb-adjusted DLCO (% predicted) based on the Crapo-Morris formula

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Supplemental Table S3. Clinical table comparing baseline demographic variables between PP participants included (with gene expression data) in or excluded (no gene expression data) from the analyses. PP SCOT Subjects Included Not Included (PP SSc Patients with Gene (PP SSc Patients w/o P-value Expression Data) Gene Expression Data) Characteristic n=63 n=4 Treatment Arm Cyclophosphamide – no. 33 1 0.3559 Transplantation – no. 30 3

Sex Female – no. (%) 38 (60.3) 3 (75.0) 1.00 Male – no. (%) 25 (39.7) 1 (25.0)

Race White – no. (%) 48 (76.2) 4 (100.0) Black/African-American 6 (9.5) 0 (0.0) – no. (%) 1.00 Asian – no. (%) 3 (4.8) 0 (0.0) Multiple/Other/Unknown 6 (9.5) 0 (0.0) – no. (%)

Age – Median (IQR) 46.0 (38.0, 52.0) 50.5 (43.3, 54.0) 0.8292

MRSS – Median (IQR) 28.5 (20.8, 35.0) 32.5 (21.8, 41.8) 0.7853 FVC – Median (IQR) 74.0 (62.0, 84.0) 78.5 (65.0, 89.3) 0.9362 DLCO – Median (IQR) 51.9 (47.9, 58.3) 59.1 (58.1, 62.0) 0.0287 SHAQ - Median (IQR) 1.3 (0.8, 1.8) 2.1 (1.4, 2.6) 0.179

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Supplemental Table S4 – Gene lists and gProfiler annotations for WGCNA modules associated with the intrinsic subset.

Gene Lists Module3 Module15 Module24 ARL13B COG2 UBXN7 SLC35B1 TRIB2 PIGU HN1 CBL ESRP2 ZNF285 POLA2 ALKBH3 AATF CCDC43 PLCG2 CLEC4D SYDE1 ZNF442 NACA METTL6 ZNF799 HMGN4 TLR1 FRAT1 MFAP2 COQ10B SRP54 PDHX GCDH EDC4 ACTR3 LRRC4 MAFF CCT7 PRPF39 SLC38A1 RPL13A PARP3 CD36 CEACAM4 PPAP2C FBLN7 SDR39U1 ANGEL1 ZNF585A OTUD4 HSPA6 SLC19A1 OSBPL6 SNPH PSMC5 FBXO3 ZNF585B ZNF506 RGS2 MAP3K3 RPL23AP32 CCT8 RCE1 VPS13D ZNF540 TTC33 CELF2 ARID3A PCP4 PWP2 ZNF225 LRRC23 WDPCP ZNF587B CKLF PTK2B CTNND2 OVGP1 ZNF208 AHCYL1 PREB HAVCR2 GDAP2 HGF APLN UFC1 FARSB DTD2 PSMA7 SCOC RETN IQSEC1 VASH2 PSMC3 ASB1 PSMB5 CELSR3 RPSAP52 XRCC4 ST8SIA4 RGS11 STT3A PSMD14 ITPKB GATB EI24 ITGAM ABTB1 FOXF1 EIF4G2 DSN1 TIMM23 ANKHD1 SNRNP48 MYBPC3 PIK3CG TMEM74B TMX2 LGALS1 CLYBL PRRC1 RAN SIPA1 SNAP23 CCNB1 DGKA SERPINI1 FAN1 HSD17B4 EIF2S2 FRAT2 PTPRE CAV2 MAP3K12 PDIA5 YARS MOCS2 SNAP29 PLEKHO2 SLC22A18AS CYP11A1 GPR89B MGAT5 R3HDM1 SPIN1 BRMS1L ASGR2 CR1L SLC9A5 EMC4 ZKSCAN3 ZNF747 TFB1M AHCY CEACAM3 LOC100128276 SIK1 MRPS23 VOPP1 PRPF8 SESN1 CCDC47 MOB3A TGFBR1 CRMP1 ATP1A1 CROT ELAC2 MCM7 CERK SOD2 RNF225 RASAL1 P4HB ZNF16 CCDC14 RFC2 H6PD NFE2 ICAM4 SLC11A2 PDE6B ZHX2 STAMBPL1 C9orf114 RPN1 CHST11 NAMPT CHST4 FIZ1 ERMP1 ZFP1 GTF2E2 FAM168B LMAN1L NCF4 SOX10 VRK3 TSPYL2 PRMT1 NEIL2 LYRM5 TMEM8A C11orf21 SSUH2 THADA ELK1 ZNF512 LONRF1 RPL19P12 MPO TREML1 CCHCR1 WDSUB1 IGBP1 ZNF57 POLR1E STMN3 TNFSF13B CEBPE AVPI1 THAP7 USP11 SNAP47 ZNF429 ZNF551 PRKCD VNN1 ROR2 RNF7 TMEM184C CNOT7 NSMCE1 RPL29P2 GALNT7 FCGR2C STARD5 EIF2B5 PAPD7 SRCAP PRKDC CD99 ANKRD32 TMPPE ARHGAP32 MSMO1 RASA1 MRPS7 PRPS2 A1BG-AS1 VCAN SH2B2 GRB7 CLPTM1L BRD9 C15orf57 LRRC47 CBY1 LYN ADAP1 CLDN7 TRAF3IP2 TGFBR3 COA5 ZNF691 KDM1A XKR8 ZBTB8OS SNAI2 ZBTB22 ACER3 ZNF549 EPRS ARIH2OS BCL2A1 ECEL1P2 NTAN1 MAP7D3 M6PR TRMT10B NCDN EEF1A1 HSH2D SLC11A1 TUBB2A TES NOP2 MTIF2 ZNF32 RPSAP58 CD68 C8orf60 PKLR ZSCAN21 LPAR5 XPO1 HPS5 EXOC4 SLC22A4 PPOX TRIM32 BRF2 LUZP1 CDK2 COX20 TOP3A PRKCDBP ZMAT3 UTP14A CRAMP1L PRMT3 AKR1A1 ARRB2 FARP1 MORF4L2 CDC37L1 JADE1 MORC2 RIOK1 IRAK3 STXBP6 TRIM11 DDHD1 ABCE1 WDR33 ANO9 RNASE3 CYC1 WDR77 AEN ZNF528 VIPR1 RAP2A ICAM3 SYNGR1 EIF2D APIP NUDT14 WDR36 N6AMT1 RASGRP4 LNX1 GSTM1 WDR59 GALNT12 PTCH1 RPL22 RASSF2 GSTA2 TRDMT1 CHRNB1 DLG1 TTC21B USP30 GPR160 EDN1 ZNF485 PSMD11 ZFP82 ASF1A TVP23C TBPL1 PON3 MINPP1 KIAA0100 GNB2L1 FOXK1 EEF2 CNPY3 SCARA3 IFT46 EHMT1 CLOCK COX15 ZNF514 PADI2 SVEP1 RPS26 PPM1G BTBD11 MALT1 TRMT11 APH1B WFDC2 ATG101 ATG12 USP22 INO80C ZNF736 KIAA0513 C1S LETMD1 POLR2D KLHDC1 CEACAM20 DDX39B SEC14L1 NPY5R AHSA1 RETSAT CREB3 ZNF132 THUMPD1 CD300A ITSN1 UTP11L NELFCD VTA1 RAB4A SOX4 RARA RP9 NUTF2 IFNAR2 CRYBB2 NDNL2 PSMC4 PLEK DENND2A SRP68 C21orf2 HKR1 PSMA4 C3orf17 MLC1 SHB HSD17B7 COLQ ZNF232 BCCIP METTL23 SERPINB1 SMAD9 PTGES3L-AARSD1 OGG1 DCTN6 ZNF79 AP2A2 AIF1 PRR7 RPS19 THUMPD3 ZHX1 TMEM245 ABI2 FAM49A GLIS1 SLC39A10 ELP6 MR1 HMGN3 MTCH2 SLA TSPAN4 MCFD2 VPRBP PTMA ESYT2 C2CD2 MSL3 SETD1B TTC3 HTT EMC1 CDCA4 MED1 SERPINA1 CAMSAP1 MCM3AP LYPLA1 ALMS1P FAM111A HAUS6 B9D2 DISP2 CHI3L2 EXOC2 PRIM2 HIRIP3 KIF3B GPSM3 GREB1 APOBEC3C GLO1 DFFB BCAS4 NR1D2 EFHD2 ISLR TBCCD1 TOMM6 COPG1 XRCC6P5 RRP1B CCDC88B TMEM217 BBX EHMT2 ANAPC7 ZNF609 MAPKBP1 KCNE3 ADAMTSL1 CD200 SEC63 CCDC15 RUVBL1 INSIG2 CCR3 AGRN AIMP1 ZC3HC1 FAM171A1 ZNF490 GP5 PARVG ERBB3 MRPL22 ABCF2 GLUD2 GARS SREK1IP1 CAMP SNX7 C6orf48 ARHGAP10 RAB9A TOMM40 RABEP1 DAPP1 RGS12 HDDC2 DCAF13 SIGLEC6 LOC441666 RBM15B GRK6 KCTD11 OR2A9P NCALD CCBL2 REPIN1 CYP4V2 MAPK1 MYOF SUMF2 EXOSC2 BTRC KIAA1715 RAD17 CECR6 TEAD1 MED10 SLC44A1 SLC29A3 MAML2 PPP3CB LAT2 KRT86 PTPN9 SNAPC5 PPAN-P2RY11 FBXO4 FAM3C PYCARD LINC00346 SCMH1 SUV420H1 DHX32 AARS B4GALT4 CD300C GPRC5C DOHH MRPL10 LDHA MRRF MIR155HG GCA RARG SCP2 ILF3 DDX55 VPS29 ZBTB41 GYG1 JPH2

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USP21 EIF5B NUP37 SNX9 CHTF8 NFKB1 CDR2L RAB29 ZNF343 VPS33B TPT1 ATG16L1 DDX60L KIF17 SAR1A CRYZL1 CASP6 TPR LTN1 IKBIP PCDHGA2 HYLS1 PTP4A2 LIG3 ZFP14 AMDHD1 RGL4 CCK ZNF202 NFRKB ZNF671 SLC1A4 SMC5 ZDHHC17 PLLP PABPN1 C11orf57 WDFY1 KLRK1 LOC728739 R3HDM4 DIO2 PSMC6 THYN1 SMYD3 TM2D3 SLC16A7 CYHR1 SH3GL3 HEXA OSBP TAF5 ZNF174 AKAP1 TMEM71 AURKC TARSL2 TTC9C PITRM1 PRDM15 ANP32A DMXL2 CBFA2T2 PALB2 ZDHHC14 ERCC3 ZSCAN22 COMMD7 NABP1 NKAIN1 UTP18 GTF2H4 LDHB TOE1 TNKS MCEMP1 RHBG RBM4 TEX261 MTERF2 RING1 C17orf100 SP100 LDHC NDUFV2 ABCF1 NIF3L1 PPIAL4B RPL7 DOCK8 LDHD THUMPD2 ARHGEF9 ZNF410 ANXA2P1 ACTG1 UBR2 PLTP SNRNP200 CHCHD3 GPATCH2L ZNF676 ERCC4 APAF1 CA14 YWHAQ MRPS30 WRAP53 ARSB TXNRD3 ADAM19 SMAGP MCM5 SLC2A8 COX10 UBE3A LYRM7 BBC3 MOCOS C22orf46 ANAPC2 ADPRM CHST14 ZNF511 EPHA10 CHODL ACAD9 EP400 SFT2D3 EXOSC5 RPS3 RNF166 GPIHBP1 MRFAP1L1 RPL15 ZNF416 PATZ1 RPL17 SMCHD1 GNB3 TBCK TTF1 ZNF430 NOL6 TDRD3 KIAA1033 AP1M2 HARS ADNP AAMP PAF1 ZNF596 SSH2 LAMC3 IK RANGRF METTL8 ERGIC3 LRRC58 DYSF DFNB31 MRPS27 PLCG1 SLC4A1AP DTNB PRPS1L1 APBB1IP MAOB INTS5 DUS1L EIF3L GPALPP1 RPL18A SMAP2 TAGLN EEF1G ANKEF1 EXOSC7 SPATA24 RPS10P7 HSD17B11 LMO1 NUCB2 XPO5 SLC35A1 PARL ZNF30 CHST2 CATSPER2 CCDC167 CDK5RAP1 MRPS18B SRSF7 RABL3 PREX1 SERPINF2 ZKSCAN4 RPL29 NRF1 LSM4 SLC12A2 GLIPR2 EPN2 CDYL CD180 GTF2IRD2 MRPL40 CHIC1 IRF1 TRPV5 EPB41L2 AKR1B1 MGC16142 ARHGEF6 SC5D AKIRIN2 LIF HMBOX1 PPIA GRHPR ZNF253 INPP1 FAM49B HBEGF AFG3L2 GLE1 C9orf64 DNPEP ZNF727 HHEX MST1 STX18 IARS MTM1 CEPT1 ITPRIPL1 CLEC4A STOX2 ACTB EIF2B2 NKAP ENO2 CCT6A ADAP2 ESPNL IMPAD1 C14orf1 ARMCX6 HS3ST3B1 ZNF738 TNFRSF8 TRIM2 ZMYM3 ADCK1 P3H1 DYNC1LI2 C5orf51 CBFA2T3 HEPACAM UBA1 ZKSCAN5 ATP5C1 NUP188 RWDD4 TSPAN32 RNF187 ENO1 TRMT61B SF3B2 KLHL12 NT5DC3 CD97 SLC2A10 LRRC41 NMRAL1 ZW10 HADHA HLA-F-AS1 EMR2 SORBS1 POGK NUP85 PCSK7 ANAPC15 LRFN2 OSCAR EFNB2 PAFAH2 TP53 ZPR1 RNF41 LCLAT1 CATSPER1 HEPH C10orf2 NSRP1 DDX23 NUDT15 NUDT19 KIAA0226L SPTLC3 FLVCR2 RPL21 USP5 ZNF589 RPL21P44 DOK1 BCAT1 IDH3A ZNF841 SYNJ2BP SYT11 FDPSP2 GMIP OR51B5 DNAJC17 ZNF607 FBXO22 NHEJ1 UBXN4 CARD16 NPIPB15 PIEZO1 ATRAID BFAR NHLRC2 CASC21 SELPLG SYCE2 PARD6A CPSF3 B3GNT9 EMG1 LINC00649 EVI2B FOXC1 ZNF263 PIGH SMG8 PIGL LOC100129361 CST7 C5orf42 DDX19B URB1-AS1 RPAIN AP2B1 LOC102723405 MFSD7 XLOC_l2_001592 COX4I1 MTFP1 ZNF443 LANCL1 ZNF93 BST1 KRT17P5 SS18 SAMM50 ZNF583 ATXN7L3B PNN BTNL8 TBX10 ZNF544 SPCS1 ZNF85 SARM1 PDZD11 CD53 PPP1R1C RFC3 NCKIPSD BARD1 VPS35 POLE4 SLC15A3 IGSF21 HAUS8 OXA1L UXS1 JOSD1 COPS8 RILPL2 COL14A1 RPL18 IQCG GALM RPL13AP3 UBL4A IL1B lnc-MACC1-1 ILKAP SLC30A9 TMSB10 SNUPN SMARCB1 FCGR2A LINC00883 LMAN2L C6orf136 CTNNBL1 SEC31A PARP1 TLR5 lnc-WRNIP1-2 EIF3F R3HCC1L FAM217B CCND2 ZNF836 SRGN lnc-ERP44-3 TSHZ2 TAPT1 DRG1 VPS53 USP14 SORL1 LINC01133 KIAA0391 MED27 RTCB ZNF732 RNA28S5 RPGRIP1 LOC102723774 WDR4 RAPGEF1 RPL3 ZNF28 VWA9 CDKN2D EBF4 TOMM70A PSMC2 RPL4 NABP2 C5orf63 GPCPD1 KRTAP4-8 CAMK2D TMEM261 SLC35A4 ZNF559 VIMP SYK LOC728061 GNPDA1 ZBTB11-AS1 TMED9 PSMD3 PDP2 LRMP LIN28B RAD1 CXorf40B TARS DTX1 POLE LIN7A HERC2P10 CNIH1 LSM12 RNF8 ADCK2 TYMP S100Z PLA2G15 SEPT8 CABLES2 AIMP2 FAF2 TAF1L SIGLEC9 FXYD1 VDAC1 ZSCAN25 MPP6 CHID1 WDR5B CARD8 SPEG ACOT4 DCTN5 POLD2 RNF113B MRPL43 CASP8 TGFB1I1 STAG3 ATG14 GMDS PCCB GLTP CCR1 MCOLN3 RNF170 NUP43 TACO1 CUL1 ZNF546 CARD17 C2orf82 RANBP6 RBM19 RRAGB MLEC ZNF461 TLN1 LOC100129888 GPAA1 URGCP LINC00339 PPIB ARSK TREML2 TTC39A PDXDC1 CCBL1 TADA1 SMS GOLGA8J LOC643802 GSTA3 RBM3 NCOA5 CSRP1 CALM1 ANAPC1P1 MYO9B SPRR2A NAA10 ST6GALNAC6 PPIE ZBTB33 ZC3H13 MME KANK4 CPT2 H2AFV IARS2 RPUSD4 DDX21 SEMA4D GDNF DARS2 RQCD1 NSMCE4A ZNF337 ZNF74 SLC43A2 INTU DDOST PLEKHA8 ATP5L POLR3B LOC554206 ADAM8 RNF212 CSNK2A2 RPS10 BNIP1 STIP1 RPL23P8 ELF4 TMEM37 HECTD3 ZNF383 NUP155 CCT5 BMS1P20 LILRA1 VIT ATP1A1-AS1 ZNF493 PRMT5 UBQLN1 NR2C1 CYBB DDX31 RPP38 PGAM5 SNRPN VPS11 RPS9 TMEM140 LRP6 ESYT1 MAPK6 CRTC3 EIF3K NUTM2B RAB27A PTPRVP

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

YARS2 BUB3 NFATC3 RPL7L1 LONP1 LOC439933 LOC100130419 C12orf43 METTL21B FAM96B PUS1 FBF1 RELT SLC8A2 CKAP2 C1orf216 VAC14 ZNF266 HUS1 MBP HSPG2 PSME1 TIPRL HEATR6 RABIF UBE2V2 TBL1X LOC646014 SUPT16H DNMBP FARSA ACYP2 LCORL SECTM1 CHADL APEX1 SPTY2D1 SUCLG1 STOML2 LOC100133315 SIGLEC5 PLA2G2C TUBGCP5 DPH7 TGIF2 EDC3 TIGD5 APOL2 CLPSL2 RNPS1 POU6F1 NOP56 CDR2 ZNF480 UNC13D ETNK2 SNRNP25 DERL1 NHP2L1 RMND1 KRTAP19-5 RNF216P1 SYT8 EARS2 ATP5B ACTR8 AMOT DHDDS TLR4 lnc-UXS1-4 RSAD1 ZNF175 TMEM41A XRCC5 JMJD7 PTPRJ SLCO4A1-AS1 ZNF773 TTLL11 RNF5 TNS3 AP2S1 lnc-AC118344.1-1 TREX2 EIF2B4 GXYLT1 STIM2 CTCF TYSND1 SNX10 SNX32 HIBCH FARS2 INTS12 ARHGAP31 ZNF547 DOK3 FBXO36 ADSL SERBP1 ZBTB9 MTMR12 LOC143666 SOWAHD USH1G BTD PTPN1 ZNF76 MAP2K5 LOC728903 DENND3 MKS1 ABHD14B MAGED2 ABCB1 RPSAP9 LOC100132741 GLT1D1 lnc-GABRE-1 ZNF595 LIN52 UBE2Z TPI1P2 NOP16 lnc-EPHA1-1 CNFN CENPK NPIPB9 C7orf49 ZNF728 SLC35B2 TDRD9 PLXNB3 GOLPH3 RPL10L ZNF672 C21orf62-AS1 PHB2 CEP19 NEO1 ZNF622 TUBGCP4 LARP7 NDUFA9 TECR AIM2 FAM25C CDC5L ZNF135 GALNT11 FTSJ2 lnc-VIP-1 SLC2A14 PSMB1 BCAS2 POLR3D DHX33 XLOC_l2_001648 LOC100129034 CNPY4 TNRC6A PLRG1 DHX9 KDM5A LOC101927686 RPS2P32 PDCL EMD PPP2R5C TAT-AS1 CCM2 DCTN3 SF3B4 INPP5B WBSCR16 TRAF3IP2-AS1 SLC12A6 SNRNP35 CFAP20 METTL18 ZMYM6NB HSPA8 LYL1 TOPBP1 CMAHP GNPAT PEX5 ADGB TCIRG1 TBC1D25 POLR2C RPA2 POLR3K KIAA0368 C5AR2 MAGED4B ZNF248 PSMA5 C19orf43 C20orf195 ARHGAP26 ZNF600 CWF19L1 ZNF669 TMEM18 SLC25A6 ARHGAP27 ATP1A4 TMCO1 DCLRE1C ZNF44 ZNF729 LRFN1 ACP6 TBC1D5 CEP57 TRAPPC6A CCDC152 PTCRA UAP1 FAM178A BTG1 KCTD10 NCAPG2 LILRB1 CCT3 MAPK8 CIAPIN1 TAF9B USP28 DENND4B GLMN NAA40 NUP93 DIS3 LOC286272 LOC606724 Module 3 - gProfiler results

# signf p-value T Q Q& Q&T/Q Q&T/T term ID t t t name t T type group depth # 1 ! 0.00000191 72 916 19 0.021 0.264 GO:0051436 BP 293 obsolete negative regulation of ubiquitin- ligase activity involved in mitotic cell cycle 1 1 ! 0.00671 127 916 20 0.022 0.157 GO:0038061 BP 80 NIK/NF-kappaB signaling 1 1 ! 0.0000915 2634 916 183 0.2 0.069 GO:0051641 BP 20 cellular localization 1 1 ! 0.0076 128 916 20 0.022 0.156 GO:0071166 BP 20 ribonucleoprotein complex localization 2 1 ! 0.00143 2002 916 142 0.155 0.071 GO:0051649 BP 20 establishment of localization in cell 2 1 ! 5.09E-07 1636 916 134 0.146 0.082 GO:0046907 BP 20 intracellular transport 2 1 ! 0.00000437 340 916 44 0.048 0.129 GO:0051169 BP 20 nuclear transport 3 1 ! 0.000003 336 916 44 0.048 0.131 GO:0006913 BP 20 nucleocytoplasmic transport 4 1 ! 0.000121 194 916 29 0.032 0.149 GO:0051168 BP 20 nuclear export 5 1 ! 0.0129 2888 916 186 0.203 0.064 GO:0033036 BP 20 macromolecule localization 1 1 ! 1.29E-07 1652 916 137 0.15 0.083 GO:0070727 BP 20 cellular macromolecule localization 2 1 ! 0.00000698 226 916 34 0.037 0.15 GO:0006403 BP 20 RNA localization 2 1 ! 0.0497 19 916 7 0.008 0.368 GO:0090672 BP 20 telomerase RNA localization 3 1 ! 0.0497 19 916 7 0.008 0.368 GO:0090685 BP 20 RNA localization to nucleus 3 1 ! 0.0497 19 916 7 0.008 0.368 GO:0090670 BP 20 RNA localization to Cajal body 4 1 ! 0.0497 19 916 7 0.008 0.368 GO:0090671 BP 20 telomerase RNA localization to Cajal body 5 1 ! 0.00385 191 916 26 0.028 0.136 GO:0051236 BP 20 establishment of RNA localization 3 1 ! 0.00254 2561 916 172 0.188 0.067 GO:0008104 BP 20 protein localization 2 1 ! 1.61E-07 1641 916 136 0.148 0.083 GO:0034613 BP 20 cellular protein localization 3 1 ! 2.12E-08 805 916 84 0.092 0.104 GO:0033365 BP 20 protein localization to organelle 4 1 ! 0.00583 245 916 30 0.033 0.122 GO:0034504 BP 20 protein localization to nucleus 5 1 ! 0.025 12 916 6 0.007 0.5 GO:1990173 BP 20 protein localization to nucleoplasm 6 1 ! 0.00257 9 916 6 0.007 0.667 GO:1903405 BP 20 protein localization to nuclear body 7 1 ! 0.00257 9 916 6 0.007 0.667 GO:1904867 BP 20 protein localization to Cajal body 8 1 ! 0.0365 8 916 5 0.005 0.625 GO:1904869 BP 20 regulation of protein localization to Cajal body 9 1 ! 0.00164 127 916 21 0.023 0.165 GO:0070972 BP 20 protein localization to endoplasmic reticulum 5 1 ! 0.0416 77 916 14 0.015 0.182 GO:0034502 BP 20 protein localization to 5 1 ! 0.00014 1960 916 144 0.157 0.073 GO:0045184 BP 20 establishment of protein localization 1 1 ! 0.00000485 510 916 57 0.062 0.112 GO:0072594 BP 20 establishment of protein localization to organelle 2 1 ! 0.000331 106 916 20 0.022 0.189 GO:0072599 BP 20 establishment of protein localization to endoplasmic reticulum 3 1 ! 0.000169 102 916 20 0.022 0.196 GO:0045047 BP 20 protein targeting to ER 4 1 ! 0.0196 1920 916 132 0.144 0.069 GO:0042886 BP 20 amide transport 1 1 ! 0.000384 228 916 31 0.034 0.136 GO:0015931 BP 20 nucleobase-containing compound transport 1 1 ! 0.00284 188 916 26 0.028 0.138 GO:0050657 BP 20 nucleic acid transport 2 1 ! 0.00284 188 916 26 0.028 0.138 GO:0050658 BP 20 RNA transport 3 1 ! 0.0133 144 916 21 0.023 0.146 GO:0051028 BP 20 mRNA transport 4 1 ! 0.00219 140 916 22 0.024 0.157 GO:0006405 BP 20 RNA export from nucleus 4 1 ! 0.0176 1898 916 131 0.143 0.069 GO:0015833 BP 20 peptide transport 1 1 ! 0.00642 1861 916 131 0.143 0.07 GO:0015031 BP 20 protein transport 2 1 ! 1.19E-07 964 916 93 0.102 0.096 GO:0006886 BP 20 intracellular protein transport 3 1 ! 0.000205 176 916 27 0.029 0.153 GO:0006611 BP 20 protein export from nucleus 4 1 ! 0.0111 279 916 32 0.035 0.115 GO:0090150 BP 20 establishment of protein localization to membrane 1

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

1 ! 0.000518 99 916 19 0.021 0.192 GO:0006613 BP 20 cotranslational protein targeting to membrane 1 1 ! 0.000182 93 916 19 0.021 0.204 GO:0006614 BP 20 SRP-dependent cotranslational protein targeting to membrane 2 1 ! 0.0365 8 916 5 0.005 0.625 GO:1904871 BP 20 positive regulation of protein localization to Cajal body 1 1 ! 0.00671 127 916 20 0.022 0.157 GO:0071426 BP 20 ribonucleoprotein complex export from nucleus 1 1 ! 0.0375 32 916 9 0.01 0.281 GO:0071431 BP 20 tRNA-containing ribonucleoprotein complex export from nucleus 2 1 ! 0.0375 32 916 9 0.01 0.281 GO:0006409 BP 20 tRNA export from nucleus 3 1 ! 0.0000599 1104 916 94 0.103 0.085 GO:0070647 BP 2 protein modification by small protein conjugation or removal 1 1 ! 0.00328 895 916 75 0.082 0.084 GO:0032446 BP 2 protein modification by small protein conjugation 2 1 ! 0.0171 807 916 67 0.073 0.083 GO:0016567 BP 2 protein ubiquitination 3 1 ! 0.0356 295 916 32 0.035 0.108 GO:0000209 BP 2 protein polyubiquitination 4 1 ! 0.00109 315 916 37 0.04 0.117 GO:0070646 BP 2 protein modification by small protein removal 1 1 ! 0.00085 299 916 36 0.039 0.12 GO:0016579 BP 2 protein deubiquitination 2 1 ! 0.0228 185 916 24 0.026 0.13 GO:0048002 BP 59 antigen processing and presentation of peptide antigen 1 1 ! 0.0286 95 916 16 0.017 0.168 GO:0002474 BP 59 antigen processing and presentation of peptide antigen via MHC class I 2 1 ! 0.0342 177 916 23 0.025 0.13 GO:0019884 BP 59 antigen processing and presentation of exogenous antigen 1 1 ! 0.0173 170 916 23 0.025 0.135 GO:0002478 BP 59 antigen processing and presentation of exogenous peptide antigen 2 1 ! 0.0416 77 916 14 0.015 0.182 GO:0042590 BP 59 antigen processing and presentation of exogenous peptide antigen via MHC class I 3 1 ! 0.0258 74 916 14 0.015 0.189 GO:0002479 BP 59 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent 4 1 ! 0.0181 124 916 19 0.021 0.153 GO:0007164 BP 165 establishment of tissue polarity 1 1 ! 0.0181 124 916 19 0.021 0.153 GO:0001736 BP 165 establishment of planar polarity 2 1 ! 0.00275 153 916 23 0.025 0.15 GO:0035567 BP 165 non-canonical Wnt signaling pathway 1 1 ! 0.00436 113 916 19 0.021 0.168 GO:0090175 BP 165 regulation of establishment of planar polarity 1 1 ! 0.00329 111 916 19 0.021 0.171 GO:0060071 BP 165 Wnt signaling pathway, planar cell polarity pathway 2 1 ! 9.22E-07 77 916 20 0.022 0.26 GO:0051437 BP 284 obsolete positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition 1 1 ! 0.0051 2012 916 140 0.153 0.07 GO:0043933 BP 150 protein-containing complex subunit organization 1 1 ! 0.00567 232 916 29 0.032 0.125 GO:0071826 BP 150 ribonucleoprotein complex subunit organization 2 1 ! 0.000218 17415 916 868 0.948 0.05 GO:0008150 BP 150 biological_process 1 1 ! 0.00781 6263 916 361 0.394 0.058 GO:0071840 BP 150 cellular component organization or biogenesis 2 1 ! 0.000936 3015 916 199 0.217 0.066 GO:0044085 BP 150 cellular component biogenesis 3 1 ! 4.05E-11 477 916 65 0.071 0.136 GO:0022613 BP 150 ribonucleoprotein complex biogenesis 4 1 ! 1.34E-08 331 916 48 0.052 0.145 GO:0042254 BP 150 ribosome biogenesis 5 1 ! 0.0166 219 916 27 0.029 0.123 GO:0022618 BP 150 ribonucleoprotein complex assembly 5 1 ! 7.77E-31 11676 916 722 0.788 0.062 GO:0008152 BP 150 metabolic process 2 1 ! 1.31E-30 10714 916 681 0.743 0.064 GO:0044238 BP 150 primary metabolic process 3 1 ! 1.08E-25 6515 916 469 0.512 0.072 GO:0009058 BP 150 biosynthetic process 3 1 ! 0.0000305 2471 916 176 0.192 0.071 GO:0009056 BP 150 catabolic process 3 1 ! 5.28E-28 11155 916 693 0.757 0.062 GO:0071704 BP 150 organic substance metabolic process 3 1 ! 2.47E-31 6358 916 477 0.521 0.075 GO:1901360 BP 150 organic cyclic compound metabolic process 4 1 ! 2.91E-26 6443 916 467 0.51 0.072 GO:1901576 BP 150 organic substance biosynthetic process 4 1 ! 1.09E-12 4690 916 329 0.359 0.07 GO:1901362 BP 150 organic cyclic compound biosynthetic process 5 1 ! 0.0000207 2022 916 151 0.165 0.075 GO:1901575 BP 150 organic substance catabolic process 4 1 ! 0.00000302 698 916 71 0.078 0.102 GO:1901361 BP 150 organic cyclic compound catabolic process 5 1 ! 4.96E-23 9511 916 606 0.662 0.064 GO:0043170 BP 150 macromolecule metabolic process 4 1 ! 5.53E-25 5264 916 401 0.438 0.076 GO:0009059 BP 150 macromolecule biosynthetic process 5 1 ! 0.00000159 1292 916 111 0.121 0.086 GO:0009057 BP 150 macromolecule catabolic process 5 1 ! 1.11E-26 5637 916 426 0.465 0.076 GO:0010467 BP 150 gene expression 5 1 ! 0.00022 144 916 24 0.026 0.167 GO:0140053 BP 150 mitochondrial gene expression 6 1 ! 2.71E-29 10197 916 655 0.715 0.064 GO:0006807 BP 150 nitrogen compound metabolic process 3 1 ! 2.89E-08 15839 916 822 0.897 0.052 GO:0009987 BP 150 cellular process 2 1 ! 0.00153 1829 916 132 0.144 0.072 GO:0007049 BP 150 cell cycle 3 1 ! 0.000671 985 916 83 0.091 0.084 GO:0000278 BP 150 mitotic cell cycle 4 1 ! 0.00128 304 916 36 0.039 0.118 GO:0045930 BP 150 negative regulation of mitotic cell cycle 5 1 ! 0.00167 1319 916 102 0.111 0.077 GO:0022402 BP 150 cell cycle process 3 1 ! 0.0000225 821 916 77 0.084 0.094 GO:1903047 BP 150 mitotic cell cycle process 4 1 ! 0.00848 574 916 53 0.058 0.092 GO:0044770 BP 150 cell cycle phase transition 4 1 ! 0.00761 542 916 51 0.056 0.094 GO:0044772 BP 150 mitotic cell cycle phase transition 5 1 ! 0.00116 329 916 38 0.041 0.116 GO:0010948 BP 150 negative regulation of cell cycle process 4 1 ! 1.22E-39 10743 916 704 0.769 0.066 GO:0044237 BP 150 cellular metabolic process 3 1 ! 7.49E-23 8307 916 549 0.599 0.066 GO:0044260 BP 150 cellular macromolecule metabolic process 4 1 ! 1.42E-07 2170 916 168 0.183 0.077 GO:0044248 BP 150 cellular catabolic process 4 1 ! 7.87E-08 1061 916 100 0.109 0.094 GO:0044265 BP 150 cellular macromolecule catabolic process 5 1 ! 0.00064 571 916 56 0.061 0.098 GO:0043632 BP 150 modification-dependent macromolecule catabolic process 6 1 ! 4.44E-31 6141 916 465 0.508 0.076 GO:0006725 BP 150 cellular aromatic compound metabolic process 4 1 ! 4.08E-07 667 916 71 0.078 0.106 GO:0019439 BP 150 aromatic compound catabolic process 5 1 ! 8.56E-32 6104 916 465 0.508 0.076 GO:0046483 BP 150 heterocycle metabolic process 4 1 ! 1.56E-07 653 916 71 0.078 0.109 GO:0046700 BP 150 heterocycle catabolic process 5 1 ! 1.03E-26 6359 916 464 0.507 0.073 GO:0044249 BP 150 cellular biosynthetic process 4 1 ! 4.01E-12 4545 916 319 0.348 0.07 GO:0019438 BP 150 aromatic compound biosynthetic process 5 1 ! 3.31E-12 4539 916 319 0.348 0.07 GO:0018130 BP 150 heterocycle biosynthetic process 5 1 ! 1.55E-25 5142 916 396 0.432 0.077 GO:0034645 BP 150 cellular macromolecule biosynthetic process 5 1 ! 1.63E-38 6636 916 510 0.557 0.077 GO:0034641 BP 150 cellular nitrogen compound metabolic process 4 1 ! 1.62E-24 5142 916 393 0.429 0.076 GO:0044271 BP 150 cellular nitrogen compound biosynthetic process 5 1 ! 0.00000018 655 916 71 0.078 0.108 GO:0044270 BP 150 cellular nitrogen compound catabolic process 5 1 ! 0.0291 128 916 19 0.021 0.148 GO:0044106 BP 150 cellular amine metabolic process 5 1 ! 1.69E-08 989 916 97 0.106 0.098 GO:0043603 BP 150 cellular amide metabolic process 5 1 ! 6.79E-10 824 916 89 0.097 0.108 GO:0006518 BP 150 peptide metabolic process 6 1 ! 3.57E-10 760 916 85 0.093 0.112 GO:0043604 BP 150 amide biosynthetic process 6 1 ! 1.74E-32 5936 916 458 0.5 0.077 GO:0006139 BP 150 nucleobase-containing compound metabolic process 5 1 ! 3.14E-33 5268 916 424 0.463 0.08 GO:0090304 BP 150 nucleic acid metabolic process 6 1 ! 4.37E-27 4753 916 379 0.414 0.08 GO:0016070 BP 150 RNA metabolic process 7 1 ! 2.32E-19 575 916 88 0.096 0.153 GO:0034660 BP 150 ncRNA metabolic process 8 1 ! 2.2E-12 188 916 40 0.044 0.213 GO:0006399 BP 150 tRNA metabolic process 9 1 ! 0.00000151 293 916 41 0.045 0.14 GO:0016072 BP 150 rRNA metabolic process 9 1 ! 0.0139 36 916 10 0.011 0.278 GO:0000959 BP 150 mitochondrial RNA metabolic process 8 1 ! 1.63E-12 824 916 95 0.104 0.115 GO:0016071 BP 150 mRNA metabolic process 8

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

1 ! 6.96E-14 945 916 107 0.117 0.113 GO:0006396 BP 150 RNA processing 8 1 ! 0.00133 426 916 45 0.049 0.106 GO:0008380 BP 150 RNA splicing 9 1 ! 0.00294 328 916 37 0.04 0.113 GO:0000375 BP 150 RNA splicing, via transesterification reactions 10 1 ! 0.00235 325 916 37 0.04 0.114 GO:0000377 BP 150 RNA splicing, via transesterification reactions with bulged adenosine as nucleophile 11 1 ! 1.04E-10 403 916 58 0.063 0.144 GO:0034470 BP 150 ncRNA processing 9 1 ! 0.00401 123 916 20 0.022 0.163 GO:0008033 BP 150 tRNA processing 10 1 ! 0.00497 74 916 15 0.016 0.203 GO:0006400 BP 150 tRNA modification 11 1 ! 0.00000598 259 916 37 0.04 0.143 GO:0006364 BP 150 rRNA processing 10 1 ! 0.0174 498 916 47 0.051 0.094 GO:0006397 BP 150 mRNA processing 9 1 ! 0.00235 325 916 37 0.04 0.114 GO:0000398 BP 150 mRNA splicing, via spliceosome 10 1 ! 0.00000111 990 916 92 0.1 0.093 GO:0006259 BP 150 DNA metabolic process 7 1 ! 4.56E-12 4475 916 315 0.344 0.07 GO:0034654 BP 150 nucleobase-containing compound biosynthetic process 6 1 ! 3.85E-09 3900 916 272 0.297 0.07 GO:0032774 BP 150 RNA biosynthetic process 7 1 ! 4.13E-09 3884 916 271 0.296 0.07 GO:0097659 BP 150 nucleic acid-templated transcription 8 1 ! 4.56E-09 3869 916 270 0.295 0.07 GO:0006351 BP 150 transcription, DNA-templated 9 1 ! 0.0442 205 916 25 0.027 0.122 GO:0071897 BP 150 DNA biosynthetic process 7 1 ! 4.31E-08 608 916 69 0.075 0.113 GO:0034655 BP 150 nucleobase-containing compound catabolic process 6 1 ! 6.68E-08 382 916 51 0.056 0.134 GO:0006401 BP 150 RNA catabolic process 7 1 ! 2.66E-08 349 916 49 0.053 0.14 GO:0006402 BP 150 mRNA catabolic process 8 1 ! 0.00282 212 916 28 0.031 0.132 GO:0000956 BP 150 nuclear-transcribed mRNA catabolic process 9 1 ! 0.00000894 1980 916 150 0.164 0.076 GO:1901566 BP 150 organonitrogen compound biosynthetic process 1 1 ! 5.63E-12 681 916 83 0.091 0.122 GO:0043043 BP 150 peptide biosynthetic process 2 1 ! 0.0000232 6751 916 401 0.438 0.059 GO:0019222 BP 150 regulation of metabolic process 1 1 ! 0.0441 896 916 71 0.078 0.079 GO:0009894 BP 150 regulation of catabolic process 2 1 ! 0.000087 6096 916 365 0.398 0.06 GO:0080090 BP 150 regulation of primary metabolic process 2 1 ! 0.00000112 6227 916 382 0.417 0.061 GO:0060255 BP 150 regulation of macromolecule metabolic process 2 1 ! 7.71E-10 4756 916 321 0.35 0.067 GO:0010468 BP 150 regulation of gene expression 3 1 ! 0.0003 705 916 66 0.072 0.094 GO:0010608 BP 150 posttranscriptional regulation of gene expression 4 1 ! 3.37E-09 4507 916 305 0.333 0.068 GO:0009889 BP 150 regulation of biosynthetic process 2 1 ! 3.59E-10 4208 916 293 0.32 0.07 GO:0010556 BP 150 regulation of macromolecule biosynthetic process 3 1 ! 0.0000383 5936 916 359 0.392 0.06 GO:0051171 BP 150 regulation of nitrogen compound metabolic process 2 1 ! 0.001 3728 916 237 0.259 0.064 GO:0006996 BP 150 organelle organization 1 1 ! 0.0000379 1205 916 101 0.11 0.084 GO:0051276 BP 150 chromosome organization 2 1 ! 0.000299 168 916 26 0.028 0.155 GO:0032200 BP 150 telomere organization 3 1 ! 0.0000552 155 916 26 0.028 0.168 GO:0000723 BP 150 telomere maintenance 4 1 ! 0.00000241 1909 916 148 0.162 0.078 GO:0033554 BP 150 cellular response to stress 1 1 ! 0.0000754 814 916 75 0.082 0.092 GO:0006974 BP 150 cellular response to DNA damage stimulus 2 1 ! 0.00000768 530 916 58 0.063 0.109 GO:0006281 BP 150 DNA repair 3 1 ! 0.000288 115 916 21 0.023 0.183 GO:0006289 BP 150 nucleotide-excision repair 4 1 ! 0.039 40 916 10 0.011 0.25 GO:0033683 BP 150 nucleotide-excision repair, DNA incision 5 1 ! 0.00389 1143 916 90 0.098 0.079 GO:0006082 BP 150 organic acid metabolic process 1 1 ! 0.00214 1127 916 90 0.098 0.08 GO:0043436 BP 150 oxoacid metabolic process 2 1 ! 0.00303 1038 916 84 0.092 0.081 GO:0019752 BP 150 carboxylic acid metabolic process 3 1 ! 0.0000171 6175 916 373 0.407 0.06 GO:0031323 BP 150 regulation of cellular metabolic process 1 1 ! 0.0068 801 916 68 0.074 0.085 GO:0031329 BP 150 regulation of cellular catabolic process 2 1 ! 8.32E-10 4440 916 304 0.332 0.068 GO:0031326 BP 150 regulation of cellular biosynthetic process 2 1 ! 3.71E-10 4117 916 288 0.314 0.07 GO:2000112 BP 150 regulation of cellular macromolecule biosynthetic process 3 1 ! 0.0191 82 916 15 0.016 0.183 GO:0033238 BP 150 regulation of cellular amine metabolic process 2 1 ! 8.13E-10 4272 916 295 0.322 0.069 GO:0019219 BP 150 regulation of nucleobase-containing compound metabolic process 2 1 ! 2.42E-08 3907 916 269 0.294 0.069 GO:0051252 BP 150 regulation of RNA metabolic process 3 1 ! 0.000319 275 916 35 0.038 0.127 GO:1903311 BP 150 regulation of mRNA metabolic process 4 1 ! 0.00277 176 916 25 0.027 0.142 GO:0061013 BP 150 regulation of mRNA catabolic process 5 1 ! 0.00000078 3717 916 252 0.275 0.068 GO:2001141 BP 150 regulation of RNA biosynthetic process 4 1 ! 6.27E-07 3709 916 252 0.275 0.068 GO:1903506 BP 150 regulation of nucleic acid-templated transcription 5 1 ! 9.68E-07 3688 916 250 0.273 0.068 GO:0006355 BP 150 regulation of transcription, DNA-templated 6 1 ! 0.00235 163 916 24 0.026 0.147 GO:0043487 BP 150 regulation of RNA stability 4 1 ! 0.000915 155 916 24 0.026 0.155 GO:0043488 BP 150 regulation of mRNA stability 5 1 ! 0.00309 425 916 44 0.048 0.104 GO:1901987 BP 150 regulation of cell cycle phase transition 1 1 ! 0.000285 237 916 32 0.035 0.135 GO:1901988 BP 150 negative regulation of cell cycle phase transition 2 1 ! 0.0406 204 916 25 0.027 0.123 GO:1902749 BP 150 regulation of cell cycle G2/M phase transition 2 1 ! 0.00309 397 916 42 0.046 0.106 GO:1901990 BP 150 regulation of mitotic cell cycle phase transition 2 1 ! 0.0000915 226 916 32 0.035 0.142 GO:1901991 BP 150 negative regulation of mitotic cell cycle phase transition 3 1 ! 0.00021 5173 916 316 0.345 0.061 GO:0044267 BP 150 cellular protein metabolic process 1 1 ! 5.74E-13 655 916 83 0.091 0.127 GO:0006412 BP 150 translation 2 1 ! 0.00285 71 916 15 0.016 0.211 GO:0002181 BP 150 cytoplasmic translation 3 1 ! 0.00000257 196 916 32 0.035 0.163 GO:0006413 BP 150 translational initiation 3 1 ! 0.0125 121 916 19 0.021 0.157 GO:0032543 BP 150 mitochondrial translation 3 1 ! 0.000228 374 916 43 0.047 0.115 GO:0006520 BP 150 cellular amino acid metabolic process 1 1 ! 6.69E-09 54 916 19 0.021 0.352 GO:0043038 BP 150 amino acid activation 2 1 ! 4.53E-09 53 916 19 0.021 0.358 GO:0043039 BP 150 tRNA aminoacylation 3 1 ! 1.62E-08 50 916 18 0.02 0.36 GO:0006418 BP 150 tRNA aminoacylation for protein translation 4 1 ! 0.00343 63 916 14 0.015 0.222 GO:0006521 BP 150 regulation of cellular amino acid metabolic process 2 1 ! 0.0201 843 916 69 0.075 0.082 GO:0030163 BP 150 protein catabolic process 1 1 ! 0.0035 693 916 62 0.068 0.089 GO:0044257 BP 150 cellular protein catabolic process 2 1 ! 0.00133 95 916 18 0.02 0.189 GO:1902750 BP 150 negative regulation of cell cycle G2/M phase transition 1 1 ! 0.0236 641 916 56 0.061 0.087 GO:0051603 BP 150 proteolysis involved in cellular protein catabolic process 1 1 ! 0.000897 434 916 46 0.05 0.106 GO:0010498 BP 150 proteasomal protein catabolic process 2 1 ! 0.00202 562 916 54 0.059 0.096 GO:0019941 BP 150 modification-dependent protein catabolic process 2 1 ! 0.00369 588 916 55 0.06 0.094 GO:0006511 BP 150 ubiquitin-dependent protein catabolic process 3 1 ! 0.000191 385 916 44 0.048 0.114 GO:0043161 BP 150 proteasome-mediated ubiquitin-dependent protein catabolic process 4 1 ! 0.0000177 73 916 18 0.02 0.247 GO:0031146 BP 150 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process 5 1 ! 0.000102 81 916 18 0.02 0.222 GO:0031145 BP 150 anaphase-promoting complex-dependent catabolic process 5 1 ! 0.000956 93 916 18 0.02 0.194 GO:0010972 BP 150 negative regulation of G2/M transition of mitotic cell cycle 1 1 ! 0.00513 65 916 14 0.015 0.215 GO:2000573 BP 150 positive regulation of DNA biosynthetic process 1 1 ! 0.0428 120 916 18 0.02 0.15 GO:0002223 BP 148 stimulatory C-type lectin receptor signaling pathway 1

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

1 ! 7.45E-07 878 916 85 0.093 0.097 GO:0044419 BP 111 interspecies interaction between organisms 1 1 ! 6.54E-08 837 916 85 0.093 0.102 GO:0044403 BP 111 symbiont process 2 1 ! 4.76E-08 775 916 81 0.088 0.105 GO:0016032 BP 111 viral process 3 1 ! 4.26E-08 188 916 34 0.037 0.181 GO:0019080 BP 111 viral gene expression 4 1 ! 5.03E-07 174 916 31 0.034 0.178 GO:0019083 BP 111 viral transcription 4 Module 15 - gProfiler results

# signf p-value T Q Q& Q&T/Q Q&T/T term ID t t t name t T type group depth # 1 ! 3.69E-14 8874 217 161 0.742 0.018 GO:0050896 BP 2 response to stimulus 1 1 ! 0.0118 4436 217 79 0.364 0.018 GO:0042221 BP 2 response to chemical 2 1 ! 0.0000686 1555 217 43 0.198 0.028 GO:1901700 BP 2 response to oxygen-containing compound 3 1 ! 0.000659 3059 217 64 0.295 0.021 GO:0010033 BP 2 response to organic substance 3 1 ! 0.000838 1007 217 31 0.143 0.031 GO:0034097 BP 2 response to cytokine 4 1 ! 3.79E-07 907 217 35 0.161 0.039 GO:0033993 BP 2 response to lipid 4 1 ! 0.0259 1188 217 31 0.143 0.026 GO:0009628 BP 2 response to abiotic stimulus 2 1 ! 3.33E-07 2277 217 60 0.276 0.026 GO:0009605 BP 2 response to external stimulus 2 1 ! 5.28E-09 3853 217 88 0.406 0.023 GO:0006950 BP 2 response to stress 2 1 ! 1.98E-13 1641 217 60 0.276 0.037 GO:0006952 BP 2 defense response 3 1 ! 8.12E-07 746 217 31 0.143 0.042 GO:0006954 BP 2 inflammatory response 4 1 ! 0.00136 667 217 24 0.111 0.036 GO:0009611 BP 2 response to wounding 3 1 ! 0.0139 559 217 20 0.092 0.036 GO:0042060 BP 2 wound healing 4 1 ! 9.89E-07 940 217 35 0.161 0.037 GO:0009607 BP 2 response to biotic stimulus 2 1 ! 0.00000102 893 217 34 0.157 0.038 GO:0043207 BP 2 response to external biotic stimulus 3 1 ! 0.00000518 7303 217 125 0.576 0.017 GO:0051716 BP 2 cellular response to stimulus 2 1 ! 0.000301 2995 217 64 0.295 0.021 GO:0070887 BP 2 cellular response to chemical stimulus 3 1 ! 0.013 1033 217 29 0.134 0.028 GO:1901701 BP 2 cellular response to oxygen-containing compound 4 1 ! 0.00541 2479 217 53 0.244 0.021 GO:0071310 BP 2 cellular response to organic substance 4 1 ! 0.00116 915 217 29 0.134 0.032 GO:0071345 BP 2 cellular response to cytokine stimulus 5 1 ! 1.43E-07 191 217 17 0.078 0.089 GO:0071216 BP 2 cellular response to biotic stimulus 3 1 ! 1.75E-30 2949 217 109 0.502 0.037 GO:0002376 BP 2 immune system process 1 1 ! 9.62E-22 1198 217 62 0.286 0.052 GO:0002252 BP 2 immune effector process 2 1 ! 1.41E-19 830 217 50 0.23 0.06 GO:0002443 BP 2 leukocyte mediated immunity 3 1 ! 3.65E-24 536 217 46 0.212 0.086 GO:0002444 BP 2 myeloid leukocyte mediated immunity 4 1 ! 1.25E-21 493 217 42 0.194 0.085 GO:0002446 BP 2 neutrophil mediated immunity 5 1 ! 0.000105 46 217 8 0.037 0.174 GO:0002448 BP 2 mast cell mediated immunity 5 1 ! 1.96E-28 2085 217 90 0.415 0.043 GO:0006955 BP 2 immune response 2 1 ! 0.00965 498 217 19 0.088 0.038 GO:0002250 BP 2 adaptive immune response 3 1 ! 5.34E-09 911 217 38 0.175 0.042 GO:0045087 BP 2 innate immune response 3 1 ! 0.014 925 217 27 0.124 0.029 GO:0002520 BP 2 immune system development 2 1 ! 0.0186 884 217 26 0.12 0.029 GO:0048534 BP 2 hematopoietic or lymphoid organ development 3 1 ! 0.00000215 1330 217 42 0.194 0.032 GO:0022610 BP 2 biological adhesion 1 1 ! 0.00000183 1323 217 42 0.194 0.032 GO:0007155 BP 2 cell adhesion 2 1 ! 0.00429 763 217 25 0.115 0.033 GO:0098609 BP 2 cell-cell adhesion 3 1 ! 0.00186 320 217 16 0.074 0.05 GO:0007159 BP 2 leukocyte cell-cell adhesion 4 1 ! 0.000027 628 217 26 0.12 0.041 GO:0030155 BP 2 regulation of cell adhesion 3 1 ! 0.0131 372 217 16 0.074 0.043 GO:0022407 BP 2 regulation of cell-cell adhesion 4 1 ! 0.013 288 217 14 0.065 0.049 GO:1903037 BP 2 regulation of leukocyte cell-cell adhesion 5 1 ! 0.0141 213 217 12 0.055 0.056 GO:1903039 BP 2 positive regulation of leukocyte cell-cell adhesion 6 1 ! 0.0221 2462 217 51 0.235 0.021 GO:0051704 BP 2 multi-organism process 1 1 ! 9.65E-07 891 217 34 0.157 0.038 GO:0051707 BP 2 response to other organism 2 1 ! 2.98E-07 588 217 28 0.129 0.048 GO:0009617 BP 2 response to bacterium 3 1 ! 1.25E-09 332 217 24 0.111 0.072 GO:0002237 BP 2 response to molecule of bacterial origin 4 1 ! 3.2E-09 315 217 23 0.106 0.073 GO:0032496 BP 2 response to lipopolysaccharide 5 1 ! 0.00000209 169 217 15 0.069 0.089 GO:0071219 BP 2 cellular response to molecule of bacterial origin 5 1 ! 0.0000102 161 217 14 0.065 0.087 GO:0071222 BP 2 cellular response to lipopolysaccharide 6 1 ! 0.00455 519 217 20 0.092 0.039 GO:0098542 BP 2 defense response to other organism 3 1 ! 0.00000716 6501 217 115 0.53 0.018 GO:0023052 BP 2 signaling 1 1 ! 4.51E-07 6400 217 117 0.539 0.018 GO:0051179 BP 2 localization 1 1 ! 3.03E-08 5145 217 104 0.479 0.02 GO:0051234 BP 2 establishment of localization 2 1 ! 7.88E-09 5040 217 104 0.479 0.021 GO:0006810 BP 2 transport 3 1 ! 6.54E-17 1982 217 72 0.332 0.036 GO:0016192 BP 2 vesicle-mediated transport 4 1 ! 0.000024 811 217 30 0.138 0.037 GO:0098657 BP 2 import into cell 4 1 ! 0.00000281 739 217 30 0.138 0.041 GO:0006897 BP 2 endocytosis 5 1 ! 0.00000004 323 217 22 0.101 0.068 GO:0006909 BP 2 phagocytosis 6 1 ! 1.36E-18 1560 217 66 0.304 0.042 GO:0046903 BP 2 secretion 4 1 ! 6.19E-20 1429 217 65 0.3 0.045 GO:0032940 BP 2 secretion by cell 5 1 ! 8.57E-22 846 217 53 0.244 0.063 GO:0006887 BP 2 exocytosis 6 1 ! 7.42E-23 735 217 51 0.235 0.069 GO:0045055 BP 2 regulated exocytosis 7 1 ! 0.031 125 217 9 0.041 0.072 GO:0002576 BP 2 platelet degranulation 8 1 ! 1.61E-24 526 217 46 0.212 0.087 GO:0043299 BP 2 leukocyte degranulation 8 1 ! 0.0282 2622 217 53 0.244 0.02 GO:0032879 BP 2 regulation of localization 2 1 ! 0.0108 2884 217 58 0.267 0.02 GO:0051239 BP 2 regulation of multicellular organismal process 1 1 ! 8.76E-10 689 217 34 0.157 0.049 GO:0001816 BP 2 cytokine production 1 1 ! 0.000221 117 217 11 0.051 0.094 GO:0071706 BP 2 superfamily cytokine production 2 1 ! 0.00129 111 217 10 0.046 0.09 GO:0032640 BP 2 tumor necrosis factor production 3 1 ! 0.000811 81 217 9 0.041 0.111 GO:0032612 BP 2 interleukin-1 production 2 1 ! 0.000116 65 217 9 0.041 0.138 GO:0032611 BP 2 interleukin-1 beta production 3 1 ! 0.0053 53 217 7 0.032 0.132 GO:0032615 BP 2 interleukin-12 production 2 1 ! 0.000313 121 217 11 0.051 0.091 GO:0032635 BP 2 interleukin-6 production 2 1 ! 9.12E-09 624 217 31 0.143 0.05 GO:0001817 BP 2 regulation of cytokine production 2 1 ! 0.00014 112 217 11 0.051 0.098 GO:1903555 BP 2 regulation of tumor necrosis factor superfamily cytokine production 3

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

1 ! 0.001 108 217 10 0.046 0.093 GO:0032680 BP 2 regulation of tumor necrosis factor production 4 1 ! 0.00014 112 217 11 0.051 0.098 GO:0032675 BP 2 regulation of interleukin-6 production 3 1 ! 0.0385 71 217 7 0.032 0.099 GO:0032652 BP 2 regulation of interleukin-1 production 3 1 ! 0.00775 56 217 7 0.032 0.125 GO:0032651 BP 2 regulation of interleukin-1 beta production 4 1 ! 0.0106 244 217 13 0.06 0.053 GO:0001818 BP 2 negative regulation of cytokine production 2 1 ! 0.0000162 196 217 15 0.069 0.077 GO:0050663 BP 2 cytokine secretion 2 1 ! 0.00307 49 217 7 0.032 0.143 GO:0050701 BP 2 interleukin-1 secretion 3 1 ! 0.00103 42 217 7 0.032 0.167 GO:0050702 BP 2 interleukin-1 beta secretion 4 1 ! 0.00000685 3322 217 73 0.336 0.022 GO:0065009 BP 2 regulation of molecular function 1 1 ! 1.04E-07 1688 217 51 0.235 0.03 GO:0044093 BP 2 positive regulation of molecular function 2 1 ! 0.00000054 2243 217 59 0.272 0.026 GO:0050790 BP 2 regulation of catalytic activity 2 1 ! 0.0000374 1188 217 37 0.171 0.031 GO:0051336 BP 2 regulation of hydrolase activity 3 1 ! 3.78E-07 1362 217 44 0.203 0.032 GO:0043085 BP 2 positive regulation of catalytic activity 3 1 ! 0.0000387 732 217 28 0.129 0.038 GO:0051345 BP 2 positive regulation of hydrolase activity 4 1 ! 0.00502 822 217 26 0.12 0.032 GO:0043086 BP 2 negative regulation of catalytic activity 3 1 ! 0.0192 298 217 14 0.065 0.047 GO:0051348 BP 2 negative regulation of transferase activity 4 1 ! 0.0000193 6519 217 114 0.525 0.017 GO:0007154 BP 2 cell communication 1 1 ! 0.00024 275 217 16 0.074 0.058 GO:0070661 BP 2 leukocyte proliferation 1 1 ! 0.000105 259 217 16 0.074 0.062 GO:0032943 BP 2 mononuclear cell proliferation 2 1 ! 0.0399 198 217 11 0.051 0.056 GO:0032944 BP 2 regulation of mononuclear cell proliferation 3 1 ! 0.00124 5669 217 98 0.452 0.017 GO:0048518 BP 2 positive regulation of biological process 1 1 ! 0.000644 1563 217 41 0.189 0.026 GO:0051240 BP 2 positive regulation of multicellular organismal process 2 1 ! 1.09E-07 410 217 24 0.111 0.059 GO:0001819 BP 2 positive regulation of cytokine production 3 1 ! 0.0237 66 217 7 0.032 0.106 GO:1903557 BP 2 positive regulation of tumor necrosis factor superfamily cytokine production 4 1 ! 0.000815 380 217 18 0.083 0.047 GO:0045785 BP 2 positive regulation of cell adhesion 2 1 ! 0.0443 929 217 26 0.12 0.028 GO:0051050 BP 2 positive regulation of transport 2 1 ! 0.0272 123 217 9 0.041 0.073 GO:0045807 BP 2 positive regulation of endocytosis 3 1 ! 8.69E-27 1359 217 72 0.332 0.053 GO:0001775 BP 2 cell activation 1 1 ! 1.33E-26 1205 217 68 0.313 0.056 GO:0045321 BP 2 leukocyte activation 2 1 ! 1.8E-26 616 217 51 0.235 0.083 GO:0002274 BP 2 myeloid leukocyte activation 3 1 ! 1.69E-22 497 217 43 0.198 0.087 GO:0036230 BP 2 granulocyte activation 4 1 ! 1.04E-22 491 217 43 0.198 0.088 GO:0042119 BP 2 neutrophil activation 5 1 ! 0.000517 56 217 8 0.037 0.143 GO:0045576 BP 2 mast cell activation 4 1 ! 2.62E-09 675 217 33 0.152 0.049 GO:0046649 BP 2 lymphocyte activation 3 1 ! 0.0413 277 217 13 0.06 0.047 GO:0042113 BP 2 B cell activation 4 1 ! 6.13E-07 446 217 24 0.111 0.054 GO:0042110 BP 2 T cell activation 4 1 ! 0.0269 307 217 14 0.065 0.046 GO:0050863 BP 2 regulation of T cell activation 5 1 ! 0.0000941 257 217 16 0.074 0.062 GO:0046651 BP 2 lymphocyte proliferation 4 1 ! 0.0105 172 217 11 0.051 0.064 GO:0042098 BP 2 T cell proliferation 5 1 ! 0.00322 554 217 21 0.097 0.038 GO:0050865 BP 2 regulation of cell activation 2 1 ! 1.83E-24 679 217 51 0.235 0.075 GO:0002263 BP 2 cell activation involved in immune response 2 1 ! 1.39E-24 675 217 51 0.235 0.076 GO:0002366 BP 2 leukocyte activation involved in immune response 3 1 ! 2.64E-24 532 217 46 0.212 0.086 GO:0002275 BP 2 myeloid cell activation involved in immune response 4 1 ! 0.0000725 44 217 8 0.037 0.182 GO:0002279 BP 2 mast cell activation involved in immune response 5 1 ! 4.72E-22 481 217 42 0.194 0.087 GO:0002283 BP 2 neutrophil activation involved in immune response 5 1 ! 4.34E-22 480 217 42 0.194 0.087 GO:0043312 BP 2 neutrophil degranulation 6 1 ! 0.0249 2001 217 44 0.203 0.022 GO:0006928 BP 2 movement of cell or subcellular component 1 1 ! 0.00847 900 217 27 0.124 0.03 GO:0051270 BP 2 regulation of cellular component movement 2 1 ! 0.0156 821 217 25 0.115 0.03 GO:2000145 BP 2 regulation of cell motility 3 1 ! 2.65E-10 4074 217 94 0.433 0.023 GO:0048583 BP 2 regulation of response to stimulus 1 1 ! 0.0000775 1446 217 41 0.189 0.028 GO:0080134 BP 2 regulation of response to stress 2 1 ! 0.00000232 779 217 31 0.143 0.04 GO:0031347 BP 2 regulation of defense response 3 1 ! 0.00665 782 217 25 0.115 0.032 GO:0032101 BP 2 regulation of response to external stimulus 2 1 ! 1.69E-07 2239 217 60 0.276 0.027 GO:0048584 BP 2 positive regulation of response to stimulus 2 1 ! 2.02E-08 449 217 26 0.12 0.058 GO:0031349 BP 2 positive regulation of defense response 3 1 ! 0.000466 582 217 23 0.106 0.04 GO:0042330 BP 2 taxis 1 1 ! 0.000452 581 217 23 0.106 0.04 GO:0006935 BP 2 chemotaxis 2 1 ! 0.00176 359 217 17 0.078 0.047 GO:0050817 BP 2 coagulation 1 1 ! 0.0381 197 217 11 0.051 0.056 GO:0050670 BP 2 regulation of lymphocyte proliferation 1 1 ! 0.0139 4997 217 86 0.396 0.017 GO:0048522 BP 2 positive regulation of cellular process 1 1 ! 0.00831 359 217 16 0.074 0.045 GO:0050867 BP 2 positive regulation of cell activation 2 1 ! 0.0177 472 217 18 0.083 0.038 GO:0051272 BP 2 positive regulation of cellular component movement 2 1 ! 0.0489 509 217 18 0.083 0.035 GO:0050878 BP 2 regulation of body fluid levels 1 1 ! 0.00163 357 217 17 0.078 0.048 GO:0007599 BP 2 hemostasis 2 1 ! 0.00134 352 217 17 0.078 0.048 GO:0007596 BP 2 blood coagulation 3 1 ! 0.00488 159 217 11 0.051 0.069 GO:0030168 BP 2 platelet activation 4 1 ! 0.0089 591 217 21 0.097 0.036 GO:0010563 BP 2 negative regulation of phosphorus metabolic process 1 1 ! 0.00867 590 217 21 0.097 0.036 GO:0045936 BP 2 negative regulation of phosphate metabolic process 2 1 ! 5.73E-13 1526 217 57 0.263 0.037 GO:0002682 BP 2 regulation of immune system process 1 1 ! 0.00138 394 217 18 0.083 0.046 GO:0002697 BP 2 regulation of immune effector process 2 1 ! 0.0161 516 217 19 0.088 0.037 GO:0002694 BP 2 regulation of leukocyte activation 2 1 ! 5.78E-12 1073 217 46 0.212 0.043 GO:0002684 BP 2 positive regulation of immune system process 2 1 ! 0.0245 347 217 15 0.069 0.043 GO:0002696 BP 2 positive regulation of leukocyte activation 3 1 ! 1.78E-11 1015 217 44 0.203 0.043 GO:0050776 BP 2 regulation of immune response 2 1 ! 1.91E-09 793 217 36 0.166 0.045 GO:0050778 BP 2 positive regulation of immune response 3 1 ! 1.25E-07 649 217 30 0.138 0.046 GO:0002253 BP 2 activation of immune response 4 1 ! 0.00000106 420 217 23 0.106 0.055 GO:0045088 BP 2 regulation of innate immune response 3 1 ! 2.21E-08 346 217 23 0.106 0.066 GO:0045089 BP 2 positive regulation of innate immune response 4 1 ! 8.16E-09 298 217 22 0.101 0.074 GO:0002218 BP 2 activation of innate immune response 5 1 ! 0.000929 3441 217 69 0.318 0.02 GO:0023051 BP 2 regulation of signaling 1 1 ! 0.0219 1668 217 39 0.18 0.023 GO:0023056 BP 2 positive regulation of signaling 2 1 ! 0.0019 66 217 8 0.037 0.121 GO:0032418 BP 2 lysosome localization 1 1 ! 0.0278 488 217 18 0.083 0.037 GO:0040017 BP 2 positive regulation of locomotion 1 1 ! 0.0117 458 217 18 0.083 0.039 GO:2000147 BP 2 positive regulation of cell motility 2 1 ! 0.000521 3390 217 69 0.318 0.02 GO:0010646 BP 2 regulation of cell communication 1

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

1 ! 0.0201 1662 217 39 0.18 0.023 GO:0010647 BP 2 positive regulation of cell communication 2 1 ! 0.0329 1384 217 34 0.157 0.025 GO:0016477 BP 2 cell migration 1 1 ! 0.000852 466 217 20 0.092 0.043 GO:0050900 BP 2 leukocyte migration 2 1 ! 0.000277 177 217 13 0.06 0.073 GO:0097529 BP 2 myeloid leukocyte migration 3 1 ! 0.0238 121 217 9 0.041 0.074 GO:0097530 BP 2 granulocyte migration 4 1 ! 0.0478 101 217 8 0.037 0.079 GO:1990266 BP 2 neutrophil migration 5 1 ! 0.024 92 217 8 0.037 0.087 GO:0072676 BP 2 lymphocyte migration 3 1 ! 0.0000263 268 217 17 0.078 0.063 GO:0060326 BP 2 cell chemotaxis 2 1 ! 0.000172 201 217 14 0.065 0.07 GO:0030595 BP 2 leukocyte chemotaxis 3 1 ! 0.00494 769 217 25 0.115 0.033 GO:0030334 BP 2 regulation of cell migration 2 1 ! 0.0016 173 217 12 0.055 0.069 GO:0002685 BP 2 regulation of leukocyte migration 3 1 ! 0.0315 46 217 6 0.028 0.13 GO:2000401 BP 2 regulation of lymphocyte migration 4 1 ! 0.0425 29 217 5 0.023 0.172 GO:2000403 BP 2 positive regulation of lymphocyte migration 5 1 ! 0.00712 442 217 18 0.083 0.041 GO:0030335 BP 2 positive regulation of cell migration 2 1 ! 0.00866 107 217 9 0.041 0.084 GO:0042107 BP 2 cytokine metabolic process 1 1 ! 0.00801 106 217 9 0.041 0.085 GO:0042089 BP 2 cytokine biosynthetic process 2 1 ! 0.00000115 6002 217 111 0.512 0.018 GO:0007165 BP 2 signal transduction 1 1 ! 0.0000197 2724 217 63 0.29 0.023 GO:0035556 BP 2 intracellular signal transduction 2 1 ! 5.08E-08 2859 217 71 0.327 0.025 GO:0007166 BP 2 cell surface receptor signaling pathway 2 1 ! 0.0406 653 217 21 0.097 0.032 GO:0019221 BP 2 cytokine-mediated signaling pathway 3 1 ! 0.0000321 3095 217 68 0.313 0.022 GO:0009966 BP 2 regulation of signal transduction 2 1 ! 0.00000405 1813 217 50 0.23 0.028 GO:1902531 BP 2 regulation of intracellular signal transduction 3 1 ! 0.000181 508 217 22 0.101 0.043 GO:1902532 BP 2 negative regulation of intracellular signal transduction 4 1 ! 0.00000283 606 217 27 0.124 0.045 GO:0002764 BP 2 immune response-regulating signaling pathway 2 1 ! 9.34E-07 576 217 27 0.124 0.047 GO:0002757 BP 2 immune response-activating signal transduction 3 1 ! 1.51E-07 280 217 20 0.092 0.071 GO:0002758 BP 2 innate immune response-activating signal transduction 4 1 ! 0.000359 181 217 13 0.06 0.072 GO:0002221 BP 2 pattern recognition receptor signaling pathway 5 1 ! 0.000106 135 217 12 0.055 0.089 GO:0002224 BP 2 toll-like receptor signaling pathway 6 1 ! 0.000412 37 217 7 0.032 0.189 GO:0002755 BP 2 MyD88-dependent toll-like receptor signaling pathway 7 1 ! 0.0000483 59 217 9 0.041 0.153 GO:0034121 BP 2 regulation of toll-like receptor signaling pathway 7 1 ! 0.00626 1521 217 38 0.175 0.025 GO:0009967 BP 2 positive regulation of signal transduction 2 1 ! 0.0128 976 217 28 0.129 0.029 GO:1902533 BP 2 positive regulation of intracellular signal transduction 3 1 ! 0.00477 2673 217 56 0.258 0.021 GO:0051246 BP 2 regulation of protein metabolic process 1 1 ! 0.0121 1564 217 38 0.175 0.024 GO:0051247 BP 2 positive regulation of protein metabolic process 2 1 ! 0.0305 95 217 8 0.037 0.084 GO:0042035 BP 2 regulation of cytokine biosynthetic process 2 1 ! 0.00189 780 217 26 0.12 0.033 GO:0030162 BP 2 regulation of proteolysis 1 1 ! 0.00438 427 217 18 0.083 0.042 GO:0052547 BP 2 regulation of peptidase activity 2 1 ! 0.00178 401 217 18 0.083 0.045 GO:0052548 BP 2 regulation of endopeptidase activity 3 1 ! 0.0334 313 217 14 0.065 0.045 GO:0051251 BP 2 positive regulation of lymphocyte activation 1 1 ! 0.00819 202 217 12 0.055 0.059 GO:0050870 BP 2 positive regulation of T cell activation 2 1 ! 0.0217 837 217 25 0.115 0.03 GO:0043549 BP 2 regulation of kinase activity 1 1 ! 0.0262 67 217 7 0.032 0.104 GO:0050764 BP 2 regulation of phagocytosis 1 1 ! 0.00775 56 217 7 0.032 0.125 GO:0070527 BP 2 platelet aggregation 1 1 ! 0.000603 456 217 20 0.092 0.044 GO:0042326 BP 2 negative regulation of phosphorylation 1 1 ! 0.00669 272 217 14 0.065 0.051 GO:0033673 BP 2 negative regulation of kinase activity 2 1 ! 0.0168 2438 217 51 0.235 0.021 GO:0032268 BP 2 regulation of cellular protein metabolic process 1 1 ! 0.0059 937 217 28 0.129 0.03 GO:0023014 BP 2 signal transduction by protein phosphorylation 1 1 ! 0.00301 905 217 28 0.129 0.031 GO:0000165 BP 2 MAPK cascade 2 1 ! 0.0257 1013 217 28 0.129 0.028 GO:0032269 BP 2 negative regulation of cellular protein metabolic process 1 1 ! 0.0436 554 217 19 0.088 0.034 GO:0031400 BP 2 negative regulation of protein modification process 2 1 ! 0.0000725 44 217 8 0.037 0.182 GO:0043303 BP 2 mast cell degranulation 1 1 ! 0.0283 1374 217 34 0.157 0.025 GO:0001932 BP 2 regulation of protein phosphorylation 1 1 ! 0.0058 776 217 25 0.115 0.032 GO:0045859 BP 2 regulation of protein kinase activity 2 1 ! 0.00136 480 217 20 0.092 0.042 GO:0071900 BP 2 regulation of protein serine/threonine kinase activity 3 1 ! 0.000739 419 217 19 0.088 0.045 GO:0001933 BP 2 negative regulation of protein phosphorylation 2 1 ! 0.00313 255 217 14 0.065 0.055 GO:0006469 BP 2 negative regulation of protein kinase activity 3 1 ! 0.000886 134 217 11 0.051 0.082 GO:0071901 BP 2 negative regulation of protein serine/threonine kinase activity 4 1 ! 0.00453 714 217 24 0.111 0.034 GO:0043408 BP 2 regulation of MAPK cascade 2 1 ! 0.000729 337 217 17 0.078 0.05 GO:0043405 BP 2 regulation of MAP kinase activity 3 1 ! 0.00626 77 217 8 0.037 0.104 GO:0043407 BP 2 negative regulation of MAP kinase activity 4 1 ! 0.0000222 171 217 14 0.065 0.082 GO:0050707 BP 2 regulation of cytokine secretion 1 1 ! 0.0183 42 217 6 0.028 0.143 GO:0050704 BP 2 regulation of interleukin-1 secretion 2 1 ! 0.00718 36 217 6 0.028 0.167 GO:0050706 BP 2 regulation of interleukin-1 beta secretion 3 1 ! 0.00986 58 217 7 0.032 0.121 GO:0042108 BP 2 positive regulation of cytokine biosynthetic process 1 1 ! 0.0126 11 217 4 0.018 0.364 GO:0042535 BP 2 positive regulation of tumor necrosis factor biosynthetic process 1 1 ! 0.0369 701 217 22 0.101 0.031 GO:0007169 BP 23 transmembrane receptor protein tyrosine kinase signaling pathway 1 1 ! 0.0163 2166 217 47 0.217 0.022 GO:0008219 BP 4 cell death 1 1 ! 0.0389 2037 217 44 0.203 0.022 GO:0012501 BP 4 programmed cell death 2 1 ! 0.0172 1907 217 43 0.198 0.023 GO:0006915 BP 4 apoptotic process 3 1 ! 0.000926 1645 217 42 0.194 0.026 GO:0010941 BP 4 regulation of cell death 1 1 ! 0.00687 1527 217 38 0.175 0.025 GO:0043067 BP 4 regulation of programmed cell death 2 1 ! 0.014 1512 217 37 0.171 0.024 GO:0042981 BP 4 regulation of apoptotic process 3 1 ! 0.0498 879 217 25 0.115 0.028 GO:0043069 BP 4 negative regulation of programmed cell death 1 1 ! 0.000317 245 217 15 0.069 0.061 GO:0072593 BP 5 reactive oxygen species metabolic process 1 1 ! 0.0000758 62 217 9 0.041 0.145 GO:0006801 BP 5 superoxide metabolic process 2 1 ! 0.000483 100 217 10 0.046 0.1 GO:1903409 BP 5 reactive oxygen species biosynthetic process 1 1 ! 0.00103 166 217 12 0.055 0.072 GO:2000377 BP 5 regulation of reactive oxygen species metabolic process 1 1 ! 0.00838 80 217 8 0.037 0.1 GO:1903426 BP 5 regulation of reactive oxygen species biosynthetic process 2 1 ! 0.000142 88 217 10 0.046 0.114 GO:2000379 BP 5 positive regulation of reactive oxygen species metabolic process 2 1 ! 0.0423 72 217 7 0.032 0.097 GO:0046209 BP 5 nitric oxide metabolic process 1 1 ! 0.000866 41 217 7 0.032 0.171 GO:1904407 BP 5 positive regulation of nitric oxide metabolic process 2 1 ! 0.0289 68 217 7 0.032 0.103 GO:0006809 BP 5 nitric oxide biosynthetic process 1 1 ! 0.000207 50 217 8 0.037 0.16 GO:1903428 BP 5 positive regulation of reactive oxygen species biosynthetic process 1 1 ! 0.00875 57 217 7 0.032 0.123 GO:0045428 BP 5 regulation of nitric oxide biosynthetic process 1 1 ! 0.000866 41 217 7 0.032 0.171 GO:0045429 BP 5 positive regulation of nitric oxide biosynthetic process 2

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

1 ! 0.0014 481 217 20 0.092 0.042 GO:0002521 BP 41 leukocyte differentiation 1 1 ! 0.0314 193 217 11 0.051 0.057 GO:0002573 BP 41 myeloid leukocyte differentiation 2

Module 24 - gProfiler results

# signf p-value T Q Q& Q&T/Q Q&T/T term ID t t t name t T type group depth # 1 ! 0.0487 6118 160 76 0.475 0.012 GO:0032502 BP 1 developmental process 1 1 ! 0.00272 5699 160 76 0.475 0.013 GO:0048856 BP 1 anatomical structure development 2 1 ! 0.0234 1960 160 35 0.219 0.018 GO:0009888 BP 1 tissue development 3 1 ! 0.00401 1262 160 28 0.175 0.022 GO:0060429 BP 1 epithelium development 4 1 ! 0.044 7343 160 87 0.544 0.012 GO:0032501 BP 1 multicellular organismal process 1 1 ! 0.00198 5232 160 72 0.45 0.014 GO:0007275 BP 1 multicellular organism development 2 1 ! 0.000581 4669 160 68 0.425 0.015 GO:0048731 BP 1 system development 3 1 ! 0.0174 644 160 18 0.113 0.028 GO:0048729 BP 1 tissue morphogenesis 1 1 ! 0.00603 536 160 17 0.106 0.032 GO:0002009 BP 1 morphogenesis of an epithelium 2

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

Supplemental Table S5. Clinical characteristics of the intrinsic subsets. Characteristic Normal-Like Inflammatory Fibroproliferative P-value (N=23) (N=20) (N=20)

Age (Years) – 46.0 (11.56) 46.0 (10.76) 43.0 (8.61) 0.755 Mean (SD)

Sex Male – no. (%) 10 (43.5) 7 (35.0) 8 (40.0) 0.928 Female – no. (%) 13 (56.5) 13 (65.0) 12 (60.0)

Race White – no. (%) 21 (91.3) 15 (75.0) 12 (60.0) 0.235 Black or African 1 (4.3) 3 (15.0) 2 (10.0) American – no. (%) Asian – no. (%) 1 (4.3) 0 2 (10.0) Native Hawaiian or 0 0 0 Other Pacific Islander – no. (%) American Indian or 0 0 0 Alaska Native – no. (%) Multiple Races – 0 1 (5.0) 4 (20.0) no. (%) Other – no. (%) 0 0 0 Unknown – no. (%) 0 1 (5.0) 0

Ethnicity Hispanic or Latino – 2 (8.7) 3 (15.0) 2 (10.0) 0.821 no. (%) Not Hispanic or 21 (91.3) 16 (80.0) 18 (90.0) Latino – no. (%)

Smoking History Current – no. (%) 2 (8.7) 0 1 (5.0) 0.211 Ever – no. (%) 5 (21.7) 6 (30.0) 3 (15.0) Never – no. (%) 16 (69.6) 14 (70.0) 16 (80.0)

Disease Duration – 27.8 (14.0) 34.7 (16.4) 21.6 (12.1) 0.039 Mean (SD)

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

Modified Rodnan 28.4(9.07) 30.4(10.36) 28.4(9.25) 0.862 Skin Score (MRSS) - Mean (SD)

Disease-modifying Anti-rheumatic Drug (DMARD) Use Within 6 Months of Randomization Yes – no. (%) 17 (73.9) 17 (85.0) 10 (50.0) 0.1 No – no. (%) 6 (26.1) 3 (15.0) 10 (50.0)

DMARD Use Ever Yes – no. (%) 20 (87.0) 18 (90.0) 13 (65.0) 0.186 No – no. (%) 3 (13.0) 2 (10.0) 7 (35.0)

Scleroderma 1.2 (0.82) 1.5 (0.83) 1.0 (0.5) 0.087 Health Assessment Questionnaire (SHAQ) – Mean (SD)

FVC (% 76.7 (17.5) 75.4 (18.1) 72.3 (11.2) 0.839 Predicted) – Mean (SD)

Hb Adjusted 53.2 (7.1) 52.1 (7.8) 53.3 (7.8) 0.198 DLCO (% Predicted) [2] – Mean (SD) [1] Gastric Antral Vascular Ectasia =GAVE [2] Hb-adjusted DLCO (% predicted) based on the Crapo-Morris formula

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

Supplemental Table S6 – Clinical characteristics of healthy controls.

Characteristic Healthy Controls (n=28) Age – Mean (SD) 46.64 (9.31) Gender Female – no. (%) 16 (57.1%) Male – no. (%) 12 (42.9%) Race White/Caucasian – no. (%) 23 (82.1%) Black – no. (%) 5 (17.9%)

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

Supplemental Table S7 – Significant differentially expressed genes between the intrinsic subsets and healthy controls.

Intrinsic Subset Genes GNB4, DDX60L, BAALC, LOC100129617, C5orf56, STAT2, SRGAP2C, IFI44, TOR1B, FAM13A, LYST, OR52K2, PLSCR1, PARP14, lnc-RPL7L1-1, C18orf25, EIF2AK2, OAS3, SAT1, HERC5, NRADDP, PIWIL4, IFIH1, CMPK2, SAP30L-AS1, TDRD7, KPTN, lnc- Inflammatory MGAT1-1, TMOD2, FUT4, IFI44L, TRIM38, TRIQK, CLEC4G, DYNLT1, IRF9, MYBPC3, NOD2, HGF, DPYD, IFIT5, JAK2, LAMP3, FAM122C, FAM13A-AS1, C3orf35, SLC31A2, SLC24A4, LINC00173, SMCHD1, HNRNPLL, REC8, CEACAM1, HIST2H2BF, DDX58, SAMD9, SLC22A15, GPD2, ERP44, LINC00482, LOC100130357, LILRB4, SCO2, ARHGAP18, LOC145474, P2RX1, ACOT9, BATF2, STAM2, CPEB2, DUSP6, AP5B1, NMI, SESTD1, SAMD9L, KIAA0319L, TMPPE, SBF2, CYSLTR1, PTX3, HCG27, BRCA1, LINC01501, SLC36A1, C8orf44, SQRDL, SCARNA16, DTX3L, PRO0628, ARHGAP24, PSTPIP2, MAK, DHRSX, DICER1, XAF1, UBQLNL, PML, LRRK2, lnc-RP11-195B21.3.1-2, IFI6, PARP9, COL8A2, ADAR, TRIM5, DMXL2, PARP12, AZI2, DHX58, TTC21A, OCRL, LOC100131829, IFI16, lnc-RP11-298P3.4.1-1, WSB1, FANCA, lnc-IL1R2-2, SCARNA7, TFEC, DLEU2L, APOBEC3B, MOSPD2, SLC9A8, APLP2, ISG15, HYMAI, LOC644656, HERC6, GRAMD1B, FAM46A, MBOAT1, STAT1, FAM209A, IFITM3, MUSTN1, SPOPL, ZCCHC2, TRIM25, DAPP1, ALPK1, CDK17, EPSTI1, NSUN7, MGC16275, LOC729603, PHF20L1, MEF2A, LAP3, RAB14, ZNF117, GALNT3, ITPK1-AS1, RHBDF2, MS4A4A, PHF11, TAP2, USP18, C4orf32, SCARNA9L, TBC1D8, XRCC4, TMEM144, CRISPLD2, DGAT1, TDRD9, SRGAP2, NME8, EIF5, IFI35, LOC729040, MS4A7, FGD2, TCN2, ASAH1, LMO2, POLD3, NAT8L, SCPEP1, KDM1B, PSMA1, LOC728392, CAND1, KIDINS220, APAF1, ZFYVE16, MGEA5, FLJ38717, MIS18BP1, ADCY4, H2AFY, PNPT1, IFIT2, CLK4, OSBPL11, GNAI1, lnc-TMEM144-1, SGK494, OASL, lnc-AC110373.1-6, MERTK, TRIM22, RTP4, DGCR11, CAPN3, WDFY3, GCNT1, PPCDC, DPRXP4, BACH1, RIN2, MX2, FBXO6, BMX, BLZF1, RSAD2, IFIT1, SLC16A3, ZCCHC6, C4orf33, LOC91450, RMI1, SLC27A3, TNFSF10, UBXN11, FAM156A, PLBD1, SRGAP2B, KIAA1033, SIAE, GNS, USP41, HMGB2, FOXI2, ERO1LB, C7orf34, KIAA1958, MPO, RNF13, RBM20, HAVCR2, RDH5, RELL1, CYP1A2, KIAA1257, PHC2, CLEC1A, TRPC6, MIR181A1HG, TMEM164, ATG7, RPS16P5, ERV3-1, LOC146795, LOC100128317, ELF2, LOC100129280, ASPHD2, SCARNA13, RCOR1, FNDC3B, C9orf72, KPNB1, LSMEM1, UPB1, PLXNB2, BFSP2-AS1, APOL4, NEAT1, LOC93444, RP2, TM6SF1, LINC00877, RPA4, LY6E, HHEX, GBP1, ATP11A, ITM2B, CYBB, HELZ2, PLA2G4A, ELMOD2, GRN, KCNE5, LOC283575, SUOX, FRMD4B, PFKFB2, CPEB3, NLN, GAB2, GPR84, SLFN11, SEMA4A, DISC1, LOC399900, CBWD5, EEF1DP3, ODF3B, FAR2, FCAR, TMEM123, STXBP3, MXD3, TEP1, COQ2, MAFB, PSEN1, SLFN12, lnc-TM4SF4-2, NFKBIZ, MAP3K5, LINC00174, TRIM21, IFIT3, RRM2, ZC3HAV1, IL21R-AS1, CSAD, CLEC4D, C1GALT1, POLI, FXYD6, USP25, SSH3, IRF7, ADAMTSL4, RPGR, SPDYE5, RTN4, PRPF40A, RAB24, TRIM34, SNX13, TIMP2, STON1, STXBP5-AS1, VMP1, LOC100506860, KCNRG, GDPD3, MPP7, TNFSF13, TNNT3, N4BP2L2, CTNNA1, TNFAIP6, CNEP1R1, SP110, CEACAM4, KDM6A, CASP10, RNASE3, GNA15, LOC100132495, CASP1, ADCY10P1, ISLR2, AKAP17A, TIGD1, CCDC9, FAM212B, BRD7P3, C1orf132, LOC100132057, CKAP4, LOC100270804, DACT1, LOC283075, KIAA1804, FAM45A, CFAP70, IDS, NHS, CENPU, PHTF1, TMEM55A, NUPL1, CNP, XLOC_l2_008130, DOCK4, OAS2, CLEC18B, TPCN2, RNF213, VCPKMT, PTPRO, PRR34-AS1, ASMT, CREB5, RNF166, ZSCAN2, LINC00115, MLKL, CLDN23, KIAA1109, CCDC170, CHUK, TOR4A, IGLL1, SSFA2, ARSB, MID1IP1, KYNU, LOC730338, RICTOR, PRCP, MICAL1, AOC3, CD274, FIG4, LILRA1, FAM198B, LBR, SYTL4, PANK2, FLJ10038, EPAS1, MTL5, DDX17, C1RL-AS1, F5, PTPRE, BNIP2, DDX60, GBP4, RCN3, RHOQ, TSPAN16, ZNF503, MYOM1, USP3, MSRB2, NOTCH2NL, ZNF667, ASAP1-IT1, PAQR6, HAL, RBPJ, RGS19, LOC100127904, SERPINA1, LOC100134237, PELI1, PICALM, TRAM2-AS1, MTMR10, lnc-WDR1-1, GNAI3, TATDN3, ZNFX1, MSRB3, MTMR6, FLVCR2, ZMYM2, HTATSF1P2, RILPL2, C9orf47, WBP4, NPHP4, GLIPR1, DLEU2, STX11, PRO2852, LOC649305, SNTB1, SLC16A5, CERS6, HERC3, FAM209B, LAMP2, GPR155, NOTCH2, RBCK1, TMTC2, KIAA0895L, AGO1, PATL1, S100A6, VIPAS39, ABHD3, LRP12, SMAD1, CTSD, TGFBR2, MVP, SNORA28, MAP2K6, FGD6, BEST1, PARP11, RSRP1, S100Z, GDAP2, LRMP, TMEM154, RABEPK, RNPEP, SRD5A1, MS4A6A, HORMAD1, P2RY1, KIAA0922, LOC100996455, XLOC_l2_015561, DAB2, SLC9A1, POLK, CXorf38, OS9, SOAT1, CARS2, TMLHE, USP4, NTNG2, VSIG8, VNN1, CPT1B, LOC101927285, SLC16A6, RNF149, CA13, SLMAP, LCP1, HMGCR, ADAP2, LETM1, SRBD1, LYG1, UBASH3B, CTSA, ATP8B4, CAPZA1, PKN2, SLC22A5, ZC3H12C, TKT, IFITM2, MTF1, ZNF230, BNIPL, OAS1, RAB44, RUNDC1, LTB4R, FAM91A1, CHST15, ZNF397, RIPK2, RAB10, IFRD1, PARP4, WARS, IDH1, ZEB1-AS1, BCL6, FAS, SIK3, TEX41, BAZ2B, ZMYND15, KIAA1468, DIAPH2, C20orf24, FAM149B1, UNC80, MFAP3, TMEM30A, PRKCE, WDR5, ACVRL1, NBR2, RNASEL, SORT1, STX12, PRRG4, NFIL3, LOC158435, KPNA2, SGMS2, TSC22D3, THBS3, ITFG1, MAP3K1, HECW2, NFKBIA, LGALS9, ACER3, MYL12A, GALC, LPCAT2, UNC93B1, SLC25A13, SLC25A24, CCRL2, ANKS1A, TRIM78P, DOCK8, LPP-AS2, HPSE, ACSL3, MGC70870, PDGFC, GSDMD, TMEM201, SLC25A53, LOC646214, NSF, ARHGEF17, NHLRC3, AGER, LOC100996412, SPATA5L1, ANKRD33B, XLOC_l2_013410, LRP1, ANXA4, TK2, PPARGC1B, ZNF396, HLA-C, HADHB, HLA-B, CSNK1G1, LOC254896, NLRP1, NABP1, ST8SIA4, KLLN, IL13RA1, SPATA6, TMEM178B, KBTBD7, TSEN34, BLVRA, TBC1D2, PSME2, SERPINB1, OAF, LOC152225, FAM49B, ST6GALNAC3, RNF146, TCF7L2, NPEPL1, GNAL, CSRNP1, CD302, F2RL1, TAP1, RPAP3, HK2, IFI30, PTK2, GCH1, RBBP8, PSRC1, FZD1, PELI2, ZNF207, CELF6, C9orf139, TSHZ3, MAP3K8, IL15, RAB8A, IL1RN, LINC01299, ARHGAP27, RNF135, XRN1, SP1, CXorf23, LAPTM4A, LINC01220, PANX2, EXOC1, LATS2, CACNA2D4, SLC12A6, LOC100128670, MUT, STX10, FAM193B, CEBPB-AS1, lnc-DNAI1-1, RPS6KC1, GTDC1, AMY1C, LOC644727, LOC606724, SLCO3A1, VCPIP1, MARC1, MR1, KLHL18, FLJ45513, PHACTR1, LOC439933, ACOXL, ANXA5, DEDD, DNAJA1P5, ZNF552, COL9A2, STK38L, SIPA1L2, FFAR4, ZMPSTE24, EXT1, HGS, DENND5A, FAM20A, EZH2, FLJ45950, REL, C2CD5, ARHGEF11, LOC103344931, CHFR, TNFAIP2, GNMT, POMP, ST3GAL6, EIF4E3, YTHDF3, HDC, INE1, CDKL5, FAM156B, IMPDH1, LOC100130442, MANBA, FKBP5, S100A10, KLF5, HDAC10, DAGLB, ARHGAP26, FAM212A, CHMP5, lnc-C5orf42-2, AZU1, GSAP, TNPO3, AATBC, HINT3, KLHL2, RHOT1, MAP4K4, NPFF, CCDC88A, ARHGDIB, FBXL13, KIAA0556, ACOX2, SH3RF1, LPAR2, BBS5, GOLGA2, GCA, CACNB4, TMED7-TICAM2, PROCA1, CACUL1, LOC441268, CSTA, IL20RB, JAG1, TMF1, ALPK3, EVI5, SH3TC1, SLC25A34, MTFR2, RENBP, MX1, SLC6A4, MCU, CHRNA10, PSAP, LOC100131929, CLTC, CREBRF, NBN, BTK, METTL4, MKNK1, SNORA16B, UBA7, TREX1, SOCS2, THEMIS2, lnc-CPM-1, TUFT1, XLOC_l2_015760, STX6, TBC1D3C, GUCY1B3, MCTP1, ARSG, COTL1, SIGLEC9, LOC102467147, LOC102724049, BCL2L2, MAP3K2, DNM3, CYP4F2, GBP2, C1RL, C6orf62, WWP2, BRD7, APPL2, IFNGR1, SEC61A2, CCNL1, SCLT1, MYO5C, C17orf85, RRM2B, OGFR, GP6, DRAP1, MPZL2, COPA, ACPP, LRRC3, PAPSS2, MCMBP, TMBIM6, KALRN, LINC00924, TNK2, ATP6V0D1, FCGRT, CASP7, C2CD2L, ACTN3, ACTB, NT5C2, CCL2, CCDC149, C1QA, SLC8A1, SLC9A4, GTPBP2, DDIAS, ANKRD50, CIDEB, ENY2, TTC7B, CAMKK2, SAMD8, GGCX, NPC2, STK17A, PARP10, INSIG1, USP49, ATG16L2, CEBPB, CYP4F3, CPNE8, CPVL, LRSAM1, CHMP2B, AMZ1, DLD, CNTLN, CD99P1, ZNF106, SPA17, HEATR5A, ASAP2, SGMS1, DACH1, ITIH4, SERPINA2, ALDH2, PPP1R17, GUSB, FAM126A, RPS15AP10, , GPR68, TLN2, ROR2, CACNA2D2, RAI2, SCN3A, SH2D1A, PERP, LINC01279, C12orf57, MYO6, LOC101927139, ABHD14A, RPL39, MATK, AKT3, ALX4, MARCH9, RTN4R, TTI1, POLR2J4, STXBP6, CD247, MYRFL, CD8A, DUSP26, LAMA3, FEZ1, CTU2, IGF2-AS, SLC16A9, SNRPD2P2, DPYSL3, FBXO15, ALDH1B1, C20orf144, TTYH1, TMEM223, KLKB1, SH2D5, RASAL1, LOC400590, DSCR8, LYRM2, ZBTB20, LPHN2, EPS8L3, KCNH5, GTF3C5, SPTBN2, CXCL12, LEPREL2, DENND2A, NOC4L, CRACR2B, LIPE, SRGAP3, HSF4, GPR176, RPS3A, CD8B, SSUH2, SLC25A4, SLC35E2B, RDX, ETNK2, AQP7, BCHE, NLE1, KRT33A, RUNX3, C1S, LOC646626, CTSF, NBPF6, SCARNA6, GSTT2B, lnc-CHST4-3, TGFBR3, RPS29, ZIC5, SLC5A2, ADORA1, HMGCLL1, FAM66D, POMGNT1, SELM, LYAR, UHRF1, GRIN2C, PPP6R2, CCDC101, SNX7, VEGFB, UGT2B15, AMOTL1, SERPINE1, SORBS1, PPAT, LOC101929494, TCAF1, ZIC1, VPS51, FETUB, FAM57A, ILVBL, KIRREL, lnc-SNURF-1, ITPRIPL1, STC1, RASD2, ADARB2-AS1, LINC01291, LARP1B, ZNF541, MYBL1, IFRD2, KCNH4, BTBD2, TSEN54, GEMIN2, NES, AK8, GPR15, FAM110D, CYP2B6, HEPACAM, TOMM20, ARHGEF16, SLC25A26, PAQR8, ESRP2, SNED1, RPUSD2, CDC20, CX3CL1, DNHD1, TBC1D16, LOC102725171, PVRIG, TMEM145, C19orf44, ASAH2, MST1R, CDC25B, IGF1, GLIS1, ST6GALNAC5, BCAR1, LINC00239, ADAMTSL2, LSR, RORB, RASGRF2, PNLIPRP1, TTC24, FAM180A, IRX2, KRT32, IER5L, RORC, ITPKA, TERC, CHMP7, GOLGA2P7, SEBOX, RAB11FIP5, GDF11, SLC22A8, ZFP41, RPS15A, PON3, CNTNAP1, C1orf64, LIN7B, FAIM2, LOC100129534, DANCR, SLC27A5, VPS9D1-AS1, SPTLC3, ROBO3, RBM48, MAGEA6, DISP2, LRRC42, FKBP11, LINC00029, KIRREL3, IRAK1, AGAP1, WBSCR17, TMEM256, IPO11, RLBP1, PNPO, ESPNL, KRT17P5, PKD2L1, CRLF1, CYP26A1, IL7R, RARG, AZIN2, COL14A1, RORA, LOC101059906, PPIL2, MST1, DLG3, METTL16, TINAGL1, USP54, C1orf21, PIPOX, FAM83G, TEAD1, MYEOV, KCNN2, CIRBP-AS1, LAG3, TSPAN1, FGF4, ATP1A3, LINC00964, SYTL2, FLJ16779, STARD7-AS1, BET1, ADAM23, OR2M7, PROSER3, LINC00574, PCP4, THRA, DMPK, ITGA11, SHD, CECR2, RPS10P7, CPXM1, NRG4, LOC102467146, ASB10, HCG18, GUCY1B2, PINLYP, FAM65A, ENDOV, PARP2, PALD1, RHOH, SLC35C1, NETO1, ZNHIT2, FUBP3, VIT, XLOC_l2_010558, LOC644277, CD3D, LRP6, NEO1, WNT10B, ZNF714, B4GALT7, TMEM44, PPCS, TMPRSS7, KHDC1, CACTIN, RPS7, lnc-CSAG1-1, PRO1082, SLC41A3, TCERG1L, ABCG5, LOC646014, SMO, LURAP1, DIS3L, RNH1, HOXC6, LINC01104, UXT, RPS18, lnc- CDH4-1, RAD51B, DBF4B, DUSP8, VWCE, AXL, CXCR3, CHAC1, TMEM221, LOC642423, LOC101929149, LOC100129461, OC90, CCDC8, LAMC2, SPTAN1, SACS, ELN, SOX3, LOC101927497, PCDHB4, AMN, GLTPD2, LMO1, MAP3K4, LNX1, PPAP2C, LOC100129447, KRT15, CCNB1, KRT86, CFH, MORC4, SLC6A17, GDF7, SCARA3, BMPR1A, CD320, SYT15, TMEM53, ZNF235, WASH5P, TMEM14A, TARP, SMOC1, SNRPD2, SKAP1, SDHAF1, NPAS2, CLCC1, BTF3, MCAT, RPS14, PPP1R16B, PRR7, PALM3, SERPING1, HYKK, ODF4, CFHR3, LRIG1, DRD3, TEFM, KCNH2, SH2D2A, LECT1, TNS4, STARD5, ATP6V1G2, NENF, HTR3A, CD2, PRDM16, PTCH1, RPS7P5, HGFAC, lnc-TSHZ1-1, LINC00523, CHST4, RPL13AP17, PCDH19, RPS5, ALKBH5, LPHN1, OSR2, ARHGEF3-AS1, LOC100996579, CCDC107, JPH2, GIPC1, FAM183A, FLJ41170, SLC2A10, LOC340357, TERT, TSTD1, CLIC3, PLEKHA1, GSC, ENDOG, LRRIQ3, SERPINA6, CRABP1, NOA1, SPDL1, F8, DNLZ, C9orf171, SERPINF2, USH1G, CFAP74, BDKRB2, PORCN, WIPF3, KLRC4, ADAMTSL1, SLC25A23, RPL39L, ATRNL1, DGCR8, PQBP1, TCOF1, HMG20B, NASP, FHL1, LINC00865, LOC101927841, ABCB1, LOC648987, G3BP1, SLC6A3, TFF1, EFNA3, SEMA4C, SNORD15A, EVX1, SHANK1, S100A7, SCD5, TSHZ1, LOC644189, FUT11, MAVS, LOC728254, MRPS2, LINC00665, ARHGAP35, APLN, CARHSP1, PRPS1, LOC79999, DPP9-AS1, JAKMIP2, TMEM59L, CST2, TMEM200C, ADH1C, TMEM230, SMAGP, NEIL1, NAT10, PHACTR4, C9orf116, TRIM2, CD6, NCCRP1, ZNF562, TMEM117, lnc-UXS1-4, GSTA3, MOCS3, C5orf45, SNORD3B-1, SLC12A3, ZNF488, LRRN4CL, WDR93, NDUFB7, MLF1, PRY2, LINC01133, MIR100HG, C20orf141, CCDC167, SREBF1, POLR2I, GCK, NEURL1B, PC, FAM57B, IGFBPL1, CTNND2, FDX1L, PPP2R2B, KANK4, ERCC4, SMCR2, IGFALS, C19orf25, TMEM14C, COL12A1, RERG, FMO6P, TOMM6, KDF1, AVPI1, CHPF, HMOX2, PDE6B, CHDH, P2RX2, NUDT10, PSD, UCP3, SRRM2-AS1, LOC728061, lnc-RTL1-2, FMNL3, SNORD17, CLSTN1, KAT6B, P2RY8, SLC25A3P1, PCDHGA2, ZNF544, KIF21A, CCDC181, SIX6, GATS, CHAT, LINC01564, HLCS, MFAP2, LINC01574, SYT3, ZHX3, HIST1H4C, LOC101928991, MMP2, PTHLH, GNB1L, ZNF446, LOC100130950, BRD3, ABHD1, IKZF3, IFT172, FAM66A, NPIPB15, CALML5, ZFPM1, C16orf13, RNFT2, LINC00923, CACNA1H, IL6, lnc-C12orf75-1, SLC9A5, BPIFB2, GLP2R, NUAK1, PKD1, PCDHGC4, ZAR1L, MAFF, MROH1, TAF6L, LOC101929696, RHEBL1, ISLR, AGFG2, LINC00659, NEIL2, ADAMTS19, ARHGAP5-AS1, RET, GLTSCR2, MAT2A, FAM138A, TCP10L, B3GALNT1, DFFA, SH2D3A, FAM20C, CRHR1-IT1, lnc-FARS2-2, EBP, SIK1, ALKBH7, REREP3, PPOX, RMRP, OLFML2B, SPRR2A, GFRA3, SHISA4, MARS, LRRN3, HTR1B, GAN, LMNA, KRTAP9-7, FBXO31, CLDN7, FOXC1, ETV2, LINC00346, CPN1, EPHB2, LYPLA2, TMEM183B, CBLB, CDKN2A, RPS6, CDC7, CACNB3, PLLP, CD3G, SAMD11, HDAC5, PRDM13, DCT, CCDC172, ZNF48, EBF4, ZNF664-FAM101A, SLC7A5P1, PAIP2B, HAPLN2, ATP2B2, PRAC2, NIPAL1, ITGA9, ORMDL3, EIF4G1, TBC1D7, SFXN4, LRRC75A-AS1, TLDC1, CHIC1, LOC389834, ZNF578, CYP11A1, KRTAP20-1, IGF2, HIST1H4I, OSBPL10, CPA5, KCNK12, PTRHD1, RHBG, EPN2, CLDN16, EPHA4, LINC00698, LINC00870, GPR37L1, SHB, MATN1-AS1, SLC6A5, SMAD5, SLC38A1, SNX32, KMT2A, SSBP3, SLCO4A1-AS1, ITIH6, LINC00087, PPT2, GPR78, LOC100130419, DDHD2, C14orf132, NSUN4, SGCD, FAM189B, ACTL8, GYLTL1B, LOC100129111, KLRK1, lnc-MMRN1-2, TMEM177, MOCOS, GPC3, KIF5C, C2CD4C, MRPL45, KIF17, P2RY4, DNAAF5, LEAP2, PAWR, PTRH1, DUSP4, LOC100996291, HOXC4, ACYP2, RMDN3, PRSS3P2, AMZ2, lnc-RASSF7-1, DOT1L, CNFN, SERPINF1, SLC22A2, RGS11, LOC150051, EYA1, TTC5, CSH2, TRIM71, LPPR3, GNRH2, ALG1L, MAP3K9, ALDH3A1, C14orf169, NELL2, CCHCR1, LMF1, LOC100130560, RPL5, CYP2F1, CAV1, PABPN1L, NMB, SSSCA1, FBXO22-AS1, ARHGEF39, LIME1, TLE1, SSTR3, DDX31, LINC01137, TBC1D26, PIEZO1, TMEM184A, lnc-WRNIP1-2, HMBS, LAMB2, GPX2, CHRND, NCAM2, SLC25A19, RETNLB, GPC4, LAMC3, CNOT3, CDR2L, IGSF21, MBD3, PRR5-ARHGAP8, ZNF219, HDGF, ERN1, RIMS4, PPY, MIR143HG, PVRL3, KLHL29, CA14, PTH2, LCE1D, ZMYND8, LOC101928738, lnc-CTH-4, SP6, ASB13, HEPH, CT55, C10orf76, TM6SF2, C9orf50, BCS1L, SETMAR, SOAT2, ITPR3, MON1A, lnc-TP53INP1-1, TMPRSS6, STEAP3, TNRC18P1, ZNF574, TMEM125, INHBE, SLC2A1, SNURF, LOC100499194, FAU, KIFC1, POLR2H, LOC101930159, HIST1H4K, CCNB1IP1, SPTSSB, ATXN7L2, SMYD5, PITX1, LRRC56, QRFP, CAND2, ZNF850, PCDHB11, ADAT3, KRT73, TLX2, THEM4, PCDHGA7, TJP2, HSPG2, STX17, SIVA1, BIRC7, TMEM171, AKT1, POT1, FBXO36, RGS12, FAM219A, FAM204A, CHODL, UBE2G2, LOC101927085, PREX2, KIF22, LOC100133286, CCL27, RNF222, PRSS3, UGT2B10, CTXN1, HIST1H4J, ARHGAP39, FBLL1, TULP3, MARVELD2, CPT1C, TMEM116, KRI1, SYBU, HGH1, S1PR1, LDB1, POMGNT2, ANKFY1, KCNK15, CD28, UCKL1, RRP7B, TMPRSS2, MRPL34, CAPN5, PLK3, VASH1, PNPLA3, MUM1, RPS16, METTL15, CELA3A, FSD1L, FOXK2, LINC00630, PCDHB13, METTL8, LIN9, C12orf65, MYRF, RPS10, MOGS, FBXO32, PRB1, RPL24, NOBOX, TSSC1, IRF2BPL, TFDP2, ECSIT, POLR3H, CATSPER2, LINC01278, PPP1R3F, HMGB4, FBRS, HSD11B1L, EVA1C, NEGR1, FN3K, CD5, PCNXL2, CHMP6, GZMM, CCDC102A, TLE2, OBSCN, WDR54, C1orf86, SALL3, VWA5A, PLXNA1, BCAT1, FUT1, CNTD2, EVPLL, SNORA71C, LOC100130673, LOC645427, NCR2, COCH, SYNGR1, REEP1, CELA2A, EFNA1, LOC643339, TFR2, ZACN, MGC45922, lnc-SDR42E1-1, C12orf10, STRBP, LOC101930506, MEGF11, CRTC1, RPL7, HIST2H4B, MSX2P1, NAT14, UBE2Q2P1, RGS16, JRK, EWSAT1, C9orf163, TOB1, ALKBH2, METRN, B3GNT7, ADCY2, NFX1, TCEAL6, HMX2, TTC22, WDR90, WDR18, TMEM61, CCDC106, COL4A4, TMEM95, TOMM34, TRPV5, PRR5, DDR1, NXT1, SHARPIN, LOC102725511, KGFLP2, KRTAP10-12, NIP7, ABHD11, SLC22A11, ANKDD1A, SRSF10, CCDC134, FAM86FP, LRRC3C, WNT10A, ZNF771, GPRC5C, EXOC3-AS1, HOXA9, KCTD2, TMEM14B, ARGFX, MMP19, RNF26, SLC41A1, DLGAP1-AS1, TTTY16, B9D1, SBK1, HIST1H4H, FLJ42393, lnc-MAB21L2-1, LINC00649, PEF1, SEMA3F, GPR88, TRAF4, RXRB, PIEZO2, OR8U1, C20orf62, TCEAL5, CAV2, HMGA2, CRLF2, ARPC5L, LDB3, TPBGL, ASIC3, PIK3R2, EDN1, HES2, LOC102723774, PLCG1, FLT4, LINC01529, COL6A2, CCDC136, LOC100294145, BCORP1, PYCRL, CREB3L1, MGAT1, lnc-RP11-389E17.1.1-1, CPNE7, GCHFR, MRPS26, NKAIN1, NSG1, TMPO-AS1, LRRC14, PPP2R3A, TGIF1, LRR1, LOC101928978, lnc-NDFIP2-2, PRAMEF5, LOC100128364, LOC100129129, SERF1B, LOC728673, IFNL1, CBFA2T2, TMEM191B, ALDH18A1, MRPL23, LOC440864, PRM2, LOC441204, ABLIM2, SPRR1B, MEF2D, PLA2G2A, GPR174, SHOX, ARHGAP44, NYX, TSNARE1, VCY, ZDHHC5, FKBP4, ESPL1, IGLV1-44, NOS3, SNAP91, MFNG, CBLL1, NKD1, C5orf42, CARNS1, LOC101927766, LY6G6D, RPS15, DDX54, HLTF, EFNB2, JAKMIP1, MUC2, PPP1R3G, HIST3H2BB, DPYSL4, ACER2, XKR9, AHSA2, SLC39A14, MTMR8, LINC00260, CDK3, PARP1, FAM106B, ERCC6L, FGFBP2, PTPRCAP, ACBD4, DMKN, AFMID, GIPR, CORO2B, ACTR5, UBA6-AS1, lnc-EYA3-1, OR5L2, OR2B2, CAD, MMP25-AS1, NCR3LG1, RPTOR, MAP3K10, LOC100131150, KCNA6, PRR12, PLTP, IL34, GDNF, ASXL1, ABHD17A, SETD5, DES, EOMES, FKBP3, LINC00322, C11orf86, MYCNOS, YTHDF1, PTPRVP, PRSS23, UPK3B, PDE1A, CASZ1, BCAT2, CT47A11, SERP2, TSHB, AHDC1, ERCC2, MXRA7, ADCYAP1R1, ACAD10, C19orf80, SLC22A31, TCFL5, APOA5, C11orf1, TPO, NTHL1, ZNF250, URB1, STAG3L2, TSACC, NR0B2, COX6B2, TROAP, PPL, RLTPR, RPS27A, TOR3A, TRO, MON2, HAR1A, SDC4, RAPH1, TDRD1, FBXL8, PRRC2B, CCDC183-AS1, NEDD4L, HECTD4, DNAH10,

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

ADAM12, CDK5R2, TNXB, IMP3, C2orf82, NPC1L1, FAM71E1, MAGEE1, LINC00883, S100A5, LDOC1L, LOC727751, DMD, SSPO, TMEM190, lnc-DYM-1, TNC, SBDS, CLPP, LOC100129434, GNAO1, LOC339988, SLC12A2, B4GALT2, ACP5, WWOX, CACNA1C, LOC102725127, GYPC, PARD6G-AS1, CAMK2N2, ALPPL2, SSR4, GPRC5D, S1PR2, ANKRD53, MIR155HG, CAMK4, GPX7, GSTA2, PAXIP1-AS2, SNCG, ZNF512B, CHST6, LOC100130920, SMCO1, KC6, KRTAP3-1, KRT13, THEM6, ANKRD33, HIST1H1D, LOC145845, LOC101927910, TMEM191A, lnc-GABRE-1, CCDC129, PROCR, SH3BP4, CHN2, KLF16, CCL5, SEPP1, ZBTB5, CLIC5, SPAG16, ACSM3, IL32, NR5A1, SPRN, C16orf59, UBAP2, DUX4, ZNF275, LOC646743, BIN1, ACTA1, ARL4D, HRC, C2orf50, HIF3A, KLF1, HAMP, RPAP1, LOC285095, HIST4H4, ZFYVE28, NUBP2, lnc-PPA2-1, ZNF418, PNO1, TESK1, SHANK2, SMAD9, CCL28, LOC100132272, CYP21A2, OR8G2, LINC00909, MUC4, RPSAP52, EVPL, PCSK4, MUC5AC, SIRT5, CD248, SPOCK2, GUK1, C3, LINC01315, LINC01512, HOXA5, MAGED1, ANKEF1, LOC100129233, TP53I13, STARD3, YPEL4, DPM3, UVSSA, LINC01115, lnc-STX18-1, ZNF620, FAM78B, ANXA2R, KDSR, GLUD1P3, SOX8, C22orf29, PACRG, EMILIN1, PI16, LINC01478, PQLC3, DUSP15, FAAHP1 PSME2, FAM126A, NUDCD1, DACT1, TMSB10, RPL10L, CDK6, CYP2J2, MYC, SEPT9, PSMA1, POTEKP, COL8A2, SMARCAD1, C10orf2, TMEM192, EIF3H, MPP7, TRMT10A, CCT2, GNB2L1, PTPRO, LDHB, NACA2, ZWINT, SLC25A5, ACTG1, RPL18A, Fibroproliferativ HMGCS1, TAF4B, RPS9, KIAA1715, FAM13A, PSMC2, TRMT112, S100A10, lnc-USP35-1, NOC3L, METAP2, LONP2, SNAPC3, TBCA, EIF3A, FEN1, SH3RF1, RUFY3, DARS2, GNPDA1, PSMA6, PNPT1, R3HDM1, TBCCD1, EIF3E, GPHN, NCL, SP140L, SF3B4, LYRM7, TYMS, MTDH, SUOX, LEF1, SLC24A1, PPARGC1B, FBXO4, IKZF4, ZSWIM1, RPL18, MLLT3, NBEA, MCM4, CAPN2, LAMP3, SLC39A10, CCT8, C1orf216, FAM98A, UTP15, CD44, NLN, POLR1B, HNRNPA0, GTF2H4, SNX9, ALG10, SLC30A9, e EPHA1, ZNF57, RDH10, SEC63, LSM12, ZNF175, C11orf63, ARMCX2, MORC2, RTP4, TUBGCP5, RPL3, EARS2, ZNF416, SLC35F6, MRPL19, MSH6, ALKBH3, CCT4, MINA, DLAT, SLC25A3, COX15, SRP14, ZNF485, ZNF790, FOXK1, ZNF285, RPS19, CENPH, TIPIN, MDH1, ENO1, DCAF13, PRIM2, PGAM4, LRRC40, TAF15, MAPK6, EIF3M, PLAG1, HACE1, MBLAC2, RIOK1, SQLE, RRS1, RWDD2B, CNP, CYP4V2, CLYBL, FUT4, TMTC4, HDAC9, TDG, HSPA9, TRMT6, RPUSD4, CDK17, NDUFB2, USMG5, USP6NL, ZMYND19, RPL22, EIF5B, ZNF512, KRR1, MSMO1, PSMB4, ADNP2, ZNF436, WDR89, HMG20A, THUMPD2, NUDT6, PSMA3, TRIM38, WDR92, YWHAG, XRCC6, RBM43, NUP107, RACGAP1, SYNJ2BP, CYP51A1, FH, TMEM182, MRRF, ZBTB9, GNPNAT1, SFPQ, SUCLA2, EBNA1BP2, DCLRE1B, RRP1, RINT1, CDADC1, MRPL38, ACVR1, RAB30, COPA, ASCC1, RPP30, C11orf57, NAA15, CCT6A, COQ3, USP14, EEF1G, CWC27, KMO, CEP97, FAM210A, NCOA3, UBA5, ARFGEF2, SS18, SOCS2, LACTB2, NAA25, ZNF583, SLC30A4, KPTN, MTM1, SKA2, ARHGAP31, NHEJ1, ZSWIM3, RUVBL1, NACA, HPRT1, PER2, WDR36, MMAA, RAD51, FER, CD38, NSUN2, WDR35, ARL5B, DARS, NUDT7, PPIAL4B, ZNF585B, AP1AR, NUP155, SRFBP1, EIF2S2, HCFC2, COX10, HAUS3, MCCC1, MBTPS2, SHCBP1, GARS, BTD, TMEM245, GNAI1, DNM1L, GABPA, LRRC41, SLC35B4, ZNF462, GTF2H3, BRF2, DPP4, UBE2Z, MNAT1, CLDN23, LRIG2, DTL, KIAA0101, SLC16A7, ZCCHC4, HNRNPD, ACAD9, STAT2, NDUFA8, LAP3, NOL7, PIN4, TRAF3IP2, POTEI, RNF25, LTV1, FBXO5, PIGN, WDR77, DDX58, TMEM18, ZNF740, FAM69A, ERCC3, SSB, PCK2, TMBIM6, TIMM17A, SNAPC5, LY6E, TRAM2, OCRL, ATP1B3, PDHX, SPG20, SNUPN, ALG2, PPIA, GLCE, SKIV2L2, HLA-F-AS1, ZNF518B, AIFM1, CCDC25, DBI, CDCA2, PRKCI, PDCD5, PSMD1, EEF1D, TBC1D5, TMX2, HNRNPM, MYL12A, UTP11L, THAP2, MAD2L1, SRRM1, IMPACT, DRG1, TPI1P2, DERL1, CUL5, GCNT1, ZBTB41, LOC101928156, TMEM123, TAF5, PLRG1, CANX, RAD1, PALB2, EP400, RWDD4, PDIA3, GNL3, RRP15, DCAF4, EIF2S1, AHCY, SLC10A7, DCAF13P3, PARP11, ATAD2B, GBP1, RETSAT, NEK3, NUP62, POLD2, USP41, FTSJ2, VPRBP, B4GALT4, AQP3, THNSL1, ETAA1, IBTK, RABGGTA, NDUFAF6, SDR42E1, RAD18, SLC1A4, PRPS2, PIGK, MAGI3, GSTP1, ZBTB14, DPP3, PRDX1, TOMM7, FAM175B, USP5, PRMT1, ZNF439, RFC1, PDP2, UBE2N, ENSA, ZNF10, LRRC3, BYSL, GMPPB, DHX33, HSPD1, CNOT7, RPL19P12, ZNF304, NABP2, UVRAG, ACVR2A, OIP5, DDX60, ATXN10, COX7C, SLC25A30, KIAA1958, UQCRFS1, SUPT16H, AP5B1, RTN4IP1, VWA9, NRIP1, TP53, EZH2, CDCA5, ZKSCAN5, RMND1, C2CD2, ALDOA, DTWD2, MYDGF, CSNK1G1, ANKIB1, PRKCE, RMI2, ATP6V1H, ZNF146, RARS, FAM178A, MAL, SHFM1, MRPL3, DNMT1, PDE12, STARD4, ZNF225, FRS2, SF3A3, CASC5, PRKD3, KIAA0020, STAMBPL1, TFCP2, RPP40, ATIC, LILRB4, CUL1, TMED10, HERC5, TGIF2, ADSL, IFI44L, HTATSF1, IRF4, NDUFB9, ZNF549, HERPUD1, TBC1D24, MAP2K5, ZHX1, SETD7, SMC5, NUDT14, FMO4, C1orf131, NUP35, SNRPF, KPNA3, UCHL3, USP18, IPO13, GOSR2, UQCRB, TRMT61B, SLC4A2, GRN, RTN4, UBE2V2, PAQR3, DBT, GMPPA, ADCK1, DDX19B, UBE2E2, ZNF251, GGCT, PAGR1, EPT1, USP46, GLTP, SMARCB1, PHAX, C12orf43, RAD54B, EML2, TCN2, MDFIC, POLR3B, FA2H, RPS3, CCT7, ANAPC15, ZNF45, CPSF2, ADAMTS4, ZMAT3, FAM102A, PPP2R1B, NUMA1, CENPW, UGCG, METTL6, SSBP1, RFX7, RPL4, SRGAP2C, CAAP1, BBS12, CTDSPL2, ERC1, CAPN7, DTX1, MALT1, COG5, ENC1, USP1, CCNYL1, NIFK, KIAA0922, PRPF31, SMARCA4, DNAJC15, ZC3H6, LAPTM4A, LINC01215, TMEM41A, OAF, GNAI2, C14orf1, NHLRC3, CLNS1A, KTI12, C2orf43, CTAGE15, ERP44, ZXDB, AASDH, CASP7, POLK, MRPL13, NOM1, ZNF480, GLE1, MRPL47, DET1, LMO7, CS, CERS6, ARL8B, MORF4L2, ZNF569, PRPS1L1, CCR9, IWS1, CCDC34, IFT46, TMEM184C, ZNF689, MORF4L1, TMF1, RPAP3, BLMH, EEA1, RFK, ZWILCH, PTBP1, ANXA2P3, EXOC2, MND1, VDAC1, CCDC22, SMPD2, NOL9, NHP2, DDX47, C4orf32, SMG6, EPB41L2, CLN5, ZNF609, ORC4, MOCS2, TLR7, SNX5, LOC389641, DDX27, KIAA1324L, SGTB, TMCO4, UBASH3B, ZW10, ADPRM, SLC25A24, SLC25A12, ZNF879, TTC37, ZNF417, POLR3D, TNFRSF10A, ZCCHC7, ANAPC7, TPI1, DPY19L4, ZCCHC14, ZNF197, RNF157, LRRC58, ZNF555, TARSL2, PDHA1, HSDL1, SMIM12, PRKAG1, SUCLG2, RBBP8, NCDN, INTS7, HOOK1, ADSS, TRAPPC11, CSNK2A2, FUT8, PPP5C, ADO, COX7A2, CD180, TMX3, RPL17, TMEM242, COPG1, INTS12, PIGO, ACVR1C, NAPEPLD, PML, KLLN, KNOP1, TCEB3, PDHB, CCAR1, EMC1, THAP9, C2CD5, ERH, NUP54, FAM76A, SEPT8, SRP68, EIF2AK2, TAB1, FBXO6, TGS1, STIM1, GFPT1, WDR46, TMED9, SRD5A1, NOD1, YWHAB, TRMT10B, NDUFS5, HADHB, MIB1, HKR1, NT5DC3, RNF41, KLHL20, QSER1, WDR43, XBP1, COG2, POLH, CCNJ, GTPBP10, SPC25, SLC4A1AP, ITCH, EIF2AK3, WDR75, SUCLG1, BPNT1, RRM2, MED27, C12orf5, PI4K2B, NFE2L3, HSPA8, ZNF669, STT3A, IPP, GPI, TSR1, NDUFA9, TSPYL5, ATP1A1, MFSD11, CNPY2, ZNF280C, HDAC2, C4orf27, PRRC1, ZNF263, IPO9, CALR, CCDC88A, TAF5L, PTAR1, HAUS2, LACE1, MYBBP1A, TBCE, NPM1, CTSO, TBP, RNGTT, RNF8, RPF1, ANXA2P1, GLO1, HS3ST3B1, AP1B1, C14orf166, YIPF5, TYSND1, ZFP69B, ARHGDIB, TULP4, BCL10, TMED2, IFI35, ERO1LB, CMPK2, MDH2, TADA2B, PDXP, ENOX2, ZNF799, RPF2, CNTRL, DDX21, TMX1, CEPT1, HRASLS2, TERF2, ARMCX5, GNPAT, APEX1, NOP58, CNIH1, ELAVL1, EXOSC7, ZNF551, ZDBF2, GUSB, DNAJC21, TTI2, HLA-C, CRTC3, POLA2, PSMB1, BTBD11, SLC5A3, ZNF69, LSG1, ZNF773, KBTBD8, NCKAP1L, LIN52, ZNF793, HIRIP3, ANAPC2, GALM, MOV10, PEX3, CCDC91, ZNF16, EDC3, LRCH1, NUF2, ACTG1P20, BAALC, GINS3, IKBKAP, SNRNP70, MYO5C, RALA, FIBP, ACSL3, DIMT1, RRP1B, FLVCR2, ZNF805, BCAS4, TMEM62, BEND5, CHI3L2, TXNDC15, MUT, GPT2, EMP1, HNRNPLL, TMA16, METTL7A, ATAD1, BIVM, EIF2B4, LINC01184, TRIM32, ZNF76, FGD6, AURKB, CMTR2, SLC35A3, RB1, ASB1, GANC, HPS5, TDP1, CD2AP, OAS3, NOC4L, NPC1L1, LMNA, NPPA, NES, LINC00523, ALX4, LAMA3, P2RX2, SPTBN4, UCKL1, lnc-TP53INP1-1, CNTNAP1, NAT10, HMX2, SERPING1, LINC00659, ARHGEF16, FXYD5, ATP6V1G2, NYX, ZIC5, LIN9, KCNQ3, FBRS, FAM180A, MIR22HG, STARD7-AS1, PORCN, TTI1, IRF2BPL, TMEM145, POLR1C, LINC01186, TDRD1, IL17REL, TSPO2, IRAK1, RERG, FAM219A, LGR6, WASH5P, B3GALT5-AS1, PIPOX, NCR2, LINC00494, SMCR2, HMG20B, PRRC2B, LOC644277, CECR2, LOC101928978, C2orf49, LOC100289580, ADAM12, SLC35E2B, PCDHB13, HMGB4, PRR5, SNED1, LOC497256, RRP7B, POLR2J4, LOC100130950, SSBP3, POU2F2, lnc-CTH-4, AKT1, ASB16-AS1, SLC22A8, KRTAP10-12, SREBF1, lnc-DYM-1, CXCL12, LAMB1, DPM3, LOC100133286, STAG3L2, REEP1, ALKBH5, LOC101928991, ZNF418, TTTY16, GPR88, TBC1D7, ACBD4, PRIMA1, MEX3D, LOC101929494, PARD6G-AS1, LOC101928738, CRABP1, DNAL4, MMP25-AS1, LOC646743, SSX3, GIPR, NAALADL2, SAMD11, CORT, HGFAC, CDX1, HLA-L, RPL3L, SLC22A10, KIRREL3, CRYAA, ERCC2, FAM109B, C15orf62, GPC4, ADARB2-AS1, EFNA1, FAM65A, KMT2B, LOC100131150, KRT73, CCDC129, GUCY1B2, LINC00969, LOC389273, EVPL, lnc-BOLA2B-1, RMRP, ZNHIT2, ZCCHC18, NEGR1, ERVMER34-1, VWCE, EYA1, LOC100130920, TLR2, LINC00311, KRTAP5-4, C9orf173-AS1, PPP6R2, USP2-AS1, LOC221814, SPTLC3, ZNF235, LIPE, LINC00870, ADIPOR1, KLKB1, lnc-DHX15-1, SLC5A2, KRT31, KCNK15, LOC100127940, lnc-C9orf50-2, lnc-MAPK15-3, AHDC1, MPP1, LOC100129534, OTOA, CRLF1, KCNH2, CSNK1G2, PROSER3, LINC00687, LOC100131831, LRRC37A5P, VASH1, GRIN2C, TLE1, FOXO6, ANKFY1, ADORA1, CSN1S1, SRXN1, PGA4, BPIFB2, FOXH1, SPRY3, TRIM71, LOC389602, MDGA1, CYP2F1, MTMR14, LINC01123, ROBO3, APOBR, DUSP8, ANKRD33, TFAP2A, GFRA3, LOC401320, lnc-OSTC-2, LOC727721, LINC01529, RAPGEF3, DNHD1, USP17L2, PCDHB4, FAM181A, SRRM3, lnc-MMRN1-2, SLC6A3, LOC148696, OBSCN, CEP104, GPR78, COL11A2, ALPPL2, WSCD2, NCAPH, TERC, ZNF578, CNOT3, SLC22A11, OLFML2B, LINC00322, DCAF12, FAM66A, GPSM1, FAM20C, LOC389834, CIRBP-AS1, MMP19, HRC, PAGE2B, DLEU7, ZDHHC23, LOC100131432, NR2F1-AS1, R3HDML, FGF1, TMEM221, LINC00999, CABP5, ANKDD1A, UPK3B, C19orf25, CARM1, WDR93, MATN1-AS1, UBE2E3, SLC41A3, LOC100132356, BCORP1, SMIM5, KRT33A, LINC01126, RASAL1, KLF1, lnc-AC112512.1-1, ZAR1L, SH2D5, VWA1, ZMIZ1-AS1, LINC00964, SLC34A1, IGF2-AS, WNK4, SLC6A5, SEC24B-AS1, OR8U1, DES, SLC16A9, KLHL33, DPYSL4, OR1S1, PPIL2, JRK, LOC101929149, SLC22A20, CHMP3, FZD10-AS1, MPEG1, GYLTL1B, PCDHGA7, LINC01122, ZBTB32, LURAP1, KRTAP6-3, LINC01104, ARSD, NSUN4, LINC01225, FMO6P, MCF2L, FBXO15, OR10H2, MCAT, lnc-NGDN-1, C9orf171, TSPAN1, LOC340357, SLC25A47, LINC00029, CLPS, LOC642423, LINC01182, SLC25A45, PRY2, HDAC5, B3GALNT1, HPN-AS1, LRP6, TEAD1, lnc- RP11-389E17.1.1-1, GDF5, MRC2, TNXB, MYEOV, C1S, lnc-SLA2-3, PLA2G5, HECTD4, DNAJC27-AS1, FLJ42393, SYT15, COX6B2, EWSAT1, ZASP, REREP3, MBNL3, RBMS2, EPHB2, TFEB, ETNK2, MKRN7P, C19orf66, TAOK2, PRDM16, SMR3A, WNT4, C9orf50, POMGNT1, lnc-USP35-3, C1orf64, GPR37L1, PC, ACTL7A, FAM66D, ANKRD13B, CLDN16, STC1, LINC00637, XLOC_l2_015203, TBC1D16, RAPH1, LOC730102, POM121L12, LYPLA2, NIPAL1, LINC00982, LINC00265, SPTAN1, LOC645427, GYPC, LINC00341, NUDT10, ESRP2, RET, CLCNKA, KLF16, CARHSP1, USH1G, DUX4, RAB1B, SEZ6, DPT, CATSPERD, CD300A, TGM2, ZFP41, SYNJ2, KCTD2, LOC642947, HTR1B, BAG1, LOC149950, LINC00106, DOT1L, LOC101927043, GUK1, NEURL1B, NCAM2, LOC100289120, LOC441455, lnc-RP11-778D12.2.1-4, CTXN1, CYP2B6, FBXL17, TAGLN, CTIF, HLA-DRA, P2RX3, NBPF6, NAT14, GABRP, DCT, CHST6, IL1R2, NAV3, OR1S2, KCNH5, MAP1LC3A, ADCY2, DSCR8, FBXO17, LAMB2, SLC5A6, AK1, GATA1, LINC01118, lnc-TUBA1C-2, DUSP4, ADAMTSL2, C9orf173, LOC150051, GPR119, DGCR8, SV2A, BCL2L15, SCARNA6, CYSTM1, DCAF12L2, SCART1, ROR2, ZNF562, CPLX2, NEO1, lnc-PPP2R2A-2, ELMOD3, KRTAP4-11, HEMGN, PABPN1L, MMACHC, CCND1, LOC100129233, lnc-CHST4-3, SCARA3, MOGS, GYPA, SALL3, GYPB, CHRND, LGALS12, KRT17P5, MRPL23, TMPRSS2, SSPO, ARFRP1, CMTM2, FKBP1B, CNFN, LOC100507747, GOLGA2P7, LOC100268168, IFNLR1, MGAT1, LRRN2, G3BP1, DLEU1, LINC00460, AHSP, DPM2, CAV2, DUXA, IL15RA, MUSK, LTA, SLC25A3P1, MYOG, LRRC10, SERPINF1, MAVS, OR9A2, HMGCLL1, ZMYND8, GPR132, SLCO4A1-AS1, TXNL1, PPP1R13B, HCAR3, TSNARE1, RNF180, MON2, TBL3, LOC101930159, PRAP1, LCE3D, C10orf54, AXL, SLC18A3, PLK3, WDR18, LEPREL2, LOC100507403, lnc-CSAG1-1, IER5L, RTN4RL1, CERS3, RNF10, SPTBN2, LOC102724930, ASPSCR1, SERPINA6, COL27A1, ABCC4, GLT1D1, YBX3, LOC100129596, DBF4B, MAFF, MROH1, KRTAP23-1, GIMAP7, OR10A4, GDF7, SLC48A1, TMCC3, NEIL1, EIF5AL1, LOC646626, MTMR8, LILRB2, PPAP2C, PHOSPHO1, LINC00260, RDX, PDPK1, PTCRA, FCGR2C, KCNH4, BLCAP, TFDP2, lnc-C12orf75-1, AGO2, C18orf12, TNS1, SNORD15A, VIT, PRLHR, MUC4, MIAT, CT55, LOC102503427, FKBP8, TBKBP1, SNORA71C, MST1, ABCC5, TTC22, SHARPIN, SPRR2A, LOC102724030, KHDC1, CALML5, EVX1, NCF2, RERE, RAD51B, KRTAP4-7, MEF2B, STRADB, SLC6A9, FAAH, CMA1, lnc-BCKDHB-1, SLC17A4, ADRB3, OR51F1, AHSA2, HDGF, LOC728061, LOC100128714, CCDC162P, MEG3, NFASC, LAMC3, IL34, SLC6A8, SNCA, TARP, ACTR3BP5, LOC255187, TMEM230, MAD2L2, IL17RA, SPDYC, KAT6B, SELENBP1, MGC45922, TCOF1, ADAM33, ATRNL1, C16orf13, RAB37, STARD3, HRH3, METRNL, GATS, ACTR5, KRTAP4-12, OR1J4, R3HDM4, LOC646014, MXI1, LOC648987, LOC101929696, PCGF5, NOBOX, FCHO2, EPS8L3, MEF2D, OSBP2, SLAMF9, YPEL3, ATOH8, MAGEA6, GLIS1, ZACN, LOC101927904, LINC00639, SHANK1, SRSF10, PAQR8, LINC00211, OR7E47P, EDN1, ISLR, BNIP3L, LOC100129069, NPRL3, NRGN, PSD, CD27, TNFSF14, ZSCAN5A, EPHX3, LINC00626, RPP25, LINC01279, SEC14L1, BCAR1, FAIM2, ARGFX, FCGR1B, MT1E, LOC102724484, SPRNP1, SORBS1, EMILIN3, TSPAN5, PACRG, LINC00630, CCDC171, TDRG1, FCGR3A, FLJ36000, TNFAIP8L2, EIF2AK1, THBS1, lnc-DES-1, SMAD5, DNAJC5G, AQP9, CELA2A, KMT2E-AS1, CA2, SHD, RBM44, lnc-CDH4-1, SEC14L1P1, GNG10, TM6SF2, RAB2B, LOC102723804, UGT2B10, LOC200830, SPI1, LOC651337, MMP25, C17orf99, SPRR2D, TMPRSS7, PEF1, LOC441204, HIGD2B, TNFRSF4, MROH6, IPO11, FDX1L, FGD3, FUT11, NULL, OPRL1, MUC2, CDC34, PPY, GIMAP1, lnc-EMX2-1, TFF1, C10orf76, HTR3A, INTU, HR, CTSS, LENG8, LOC100128002, CDC27, TRPM5, PLCB2, FIBCD1, UGT3A1, PRAC2, FAM107A, ZNF488, lnc-UXS1-4, CDK5R2, FAM106B, IFNL2, TPBGL, HSF4, RBM38, TH, EPB42, ACY3, LOC100129129, KRTAP10-8, FETUB, ABTB1, LOC102725284, RARG, FAM49A, PPCS, lnc-RP11-410N8.4.1-2, LINC01347, ACER1, UBALD1, KRTAP11-1, BPGM, ZAN, CFAP74, LOC101927151, PPBP, TGFB1I1, ODF4, ITGAX, LHB, DEFB4A, SCML4, PTAFR, DERL3, TRIM3, TTLL4, FGR, LONRF3, LMF1, RBMY1B, GABRB1, TJP2, GPR25, ZNF664-FAM101A, CST2, LYRM2, GPRC5C, HAGH, INSL3, FAM186B, CELA2B, PECAM1, AOAH, RSPH14, FOXO3, ALOX5, FAM210B, KCNC3, SLC2A10, GNAS, LOC101927857, DNAH14, ALOX5AP, STMN1, HSD17B14, S100A12, SHISA4, STXBP6, PPP1R3G, RAVER1, PIEZO2, TMEM183B, SCGB3A2, CTRC, NOTCH3, SFTPC, RHCE, ZNF446, KRT32, SH3BP4, ZNF665, MSI2, AMN, LCP2, LOC100422737, UBAP1, TLR8, SYNGR1, KIR2DL4, TEFM, CCDC101, CHD1L, RARA, SPAG8, COL14A1, CREB3L1, lnc-TSHZ1-1, CCDC78, CRYGA, ANKRD9, FAXDC2, PCDHA5, TOLLIP-AS1, DRD3, LOC100132593, GALT, LST1, NKX2-3, ATXN7, LOC388210, NFAM1, DPEP2, LOC101928303, BCAT1, VWA2, PRO1082, C1orf198, KCNN2, XLOC_l2_013837, lnc-CCDC8-1, NIP7, LMO1, PIK3CD, QRFP, SPTA1, ANK1, CA1, TMEM86B, LINC01002, CLC, IGF2BP2, OC90, GSTA3, RASD2, CHN2, PAGE2, TAPT1-AS1, TFDP1, PQLC3, DCAF6, PRB1, CYP2D6, XLOC_l2_001961, FOXI3, HMBS, ZER1, CCL5, C1orf116, CSF1, KCNJ2, PRDM13, ELN, OR7E24, CTBP2, CXCR2P1, UBXN6, GPR45, KLC3, DEFA3, CBX7, TNC, UGT2B15, LILRA6, CNTD2, GZMB, TNFRSF10C, FLJ40288, UBE2O, TROAP, OR2B2, GATSL2, LOC102725127, GSTT2B, RNH1, SLC43A2, LINC01137, PI3, C11orf42, GRIN2A, OR5L2, PF4, SMOC1, LPHN2, PLEK2, GPER1, GRASPOS, NEDD4L, SPRR1A, MARS, LOC645261, MKRN1, NLRP12, PRR21, ERN1, CCDC181, ABCC10, TNRC18P1, CAND1.11, C2CD4C, TNK1, GPC3, STK10, DENND2A, LOC339807, KIAA1024, SLC22A31, DPCD, LOC100129461, LOC102467146, CTRB2, LNX1, ZNF574, DDN, lnc-ST3GAL1-1, PKD2L1, BTBD2, LOC100129931, SMCO1, LOC643339, NR0B1, ODF3, lnc-KLF7-1, OR51I2, KIF26B, HCRT, NFE2, USP17L25, lnc-SNCA-2, LOC100132272, SCGB2B2, SELK, OTUD6A, MUC5AC, GUCD1, FCGR2A, LOC100129111, LOC100130456, ASB13, LRRN4CL, TESC, EMC9, MFAP2, PDZRN3-AS1, TNIP1, MIR143HG, SLC4A1, NEUROG3, lnc-STX18-1, MS4A18, LRG1, LINC01192, CDCP2, LOC100506499, PPM1A, ARID5A, NCF1B, LOC283585, LOC100129115, CCDC23, SRGN, OR4X2, MDK, DPYSL3, FAM104A, PPAN, PNLIPRP1, KRTAP10-3, XLOC_l2_015786, MED25, POC1B, ACOT11, LPHN1, LINC00423, LBX2-AS1, AIG1, GPX2, ACER2, LOC100133985, LOC100287225, HSPG2, GIMAP5, SMOX, GZMK, CFP, OR6W1P, MARCH8, ARHGEF15, ARHGAP32, LOC102724833, ORMDL3, KCNK3, SLC25A39, SLC7A7, ANKRD53, ACRBP, KRT86, DLGAP1-AS1, PRELID1, PCDHGA2, MAP1LC3B, SNX7, LDHD, AP1M2, GADD45A, CASC15, XLOC_l2_001324, LOC100506136, GSPT1, MIR124-2HG, FRMPD3, CYP26A1, FCN1, C11orf87, UHRF1, LOC100130419, PRSS3, FAM183A, EVA1C, SIGLEC14, NCOA4, AGBL1, FAM120C, SLC26A11, ATXN7L2, SEBOX, CCR7, LOC101927139, PRR5-ARHGAP8, NHLH2, METTL15, ARHGAP25, TMEM53, FKBP4, lnc-SEPT7L-1, STRN4, lnc-AEBP1-1, XLOC_l2_010831, TACR2, GLYATL3, FLJ40039, TMEM184A, CDKL1, LSR, LOC145845, BCHE, ODF3L2, PPOX, GNLY, FGFR1OP2, lnc-WRNIP1-2, TMEM82, CDKN2A, NCF4, BLVRB, CHRFAM7A, CD82, KCND3, AQP7, C19orf33, SNORD3B-1, ALDH3B1, GTPBP6, CCDC8, LOC102723774, PRRT1, SRGAP3, CCIN, OR2H1, SLC25A19, VNN2, KIF20B, SETD5, B3GNT7, CACTIN, CYP4F62P, TBC1D26, RMND5A, DNAJC22, DPP9-AS1, OR11A1, TNNI1, WHAMMP1, SEC14L4, BAALC-AS2, KLC2, lnc-C9orf69-2, CCDC7, KRTAP20-1, MYO15B, CXCR2, TMEM171, GPR142, SOD2, ABHD5, CLEC12A, EMILIN1, FLJ41170, HCG18, PCP2, HCAR2, VCY, ACHE, CLDN4, SPINK7, SLC16A11, QPRT, OR1L3, WBSCR17, CA14, JPH2, LOC100996291, CELA3A, DOK3, TCP11L2, LINC01278, LOC440864, CX3CL1, CTSLP2, SLC25A37, MAX, ATXN8, ZDHHC5, FMNL3, AGBL4, LINC00698, TAF6L, DDAH1, TANGO2, UBR2, KDM8, RNF222, lnc-SIK1-5, LRRC16B, TMEM59L, MED24, LOC100507420, RANBP10, LOC101060524, RABGAP1L, MAGEB2, LINC00472, PBLD, XLOC_l2_009886, MTURN, FIGNL2, HIST3H2BB, BMS1P6, C12orf10, CCL15, TMEM234, CSF1R, KRTAP9-7, NPL, HIST1H2BN, lnc-WDR27-1, CLCNKB, SNX3, LOC100129763, PIP4K2C, CEP57L1, SIK1, SLC7A5P1, MYRF, PATE3, SHISA7, ENKUR, ENTPD5, SOAT2, GPIHBP1, FCER1A, BRD4, PHF21B, LOC102723521, KLF14, GP1BB, FGFBP2, RTN3, ZNF714, BCL2L1, DAB1, SEPP1, HAS1, AVPI1, SH3GL1, TPTE2P6, HLA-DMB, GLTPD2, BTNL10, PCDH1, TSPAN10, CALML4, LOC100996535, CHST11, C2orf88, FAM63A, KREMEN1, KRT7, RPIA, SHB, COL12A1, CRABP2, LINC00958, CRHR2, KRT1, WDR45, lnc-LONRF1-2, NKX1-2, TFDP3, EBF4, SLC35C2, CHMP6, C20orf62, SYNE1, lnc-PLEKHH2-1, APBB1IP, ADAMTS19, ACE, UBE2H, CIITA, BIN2, FAM129A, lnc-MOXD1-1, C2orf73, ATP5A1, CCDC157, PRR7, TMEM252, VLDLR, NBEAL2, RASSF10, FBXO9, IRX2, CT47A11, HPS1, ACAD10, FECH, GMPR, PPP2R5B, IPW, FGF4, PDZK1IP1, CENPVP2, MSN, KDM4B, INHBC, KRTAP3-3, EIF4G1, ASXL1, NR5A1, CDR2L, ROPN1L, PIM1, CST3, MOCS3, BEST2, lnc-CKAP2L-1, YIPF3, PITX3, MYRFL, TTC16, WIPF3, RHAG, KCNK9, ZHX3, HMX3, ZNRF3, PPP3R1, TREML1, NINJ2, GPR15, FXYD1, LARP1B, CTSE,

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

FNDC9, GZMA, SLC9A5, ATP1B2, MYO1F, NKAIN1, LOC102723564, WDR55, USP12, ZIC1, CNTNAP5, CDC14C, NDUFB7, SLC35D2, IGDCC3, ACR, SVEP1, GRB14, RGS12, WHAMM, LOC100653296, SERPINE1, ITGA9, OTOS, MAB21L3, B3GNT8, POLL, BST1, LILRB3, LIN7B, BTNL8, KLRF1, H2AFJ, NHSL2, MOB3A, SHISA8, TRAPPC5, KRTAP3-1, FAM204A, RALBP1, PCYT2, SNORA73B, KIRREL, INHBE, MSL1, ALOXE3, YPEL5, CKLF, LILRA3, LINC00887, NSUN3, HAR1A, INTS1, SKP1, ZBTB3, CHDH, CCL3L3, CEACAM19, LINC00469, PRSS33, TTC24, lnc-RTL1-2, LILRA4, TUBB1, BABAM1, UCKL1-AS1, C1QTNF9B-AS1, VWA7, NUPR1, CATSPER2, LOC100129447, CD14, DCST2, CRLF2, PLEKHO2, ISCA1, C17orf53, SETD8, lnc-TNFRSF18-1, RHBG, ZNF890P, DSCR9, DMPK, FAAHP1, PRDX6, OR2W3, RFX2, LOC100505984, LOC389033, LINC01115, BAI2, CARD14, lnc-TMC7-1, SPOCK2, RAC3, ABHD11, ATP1A3, RAB3IL1, FPR1, LOC100130560, LINC00923, MBP, LINC00092, HNRNPA2B1, PTPRVP, LY96, HOXA10, LOC100996349, RNF187, HCK, SMAD9, RASGRP2, FHL1, GATA3-AS1, TMEM54, CDC42EP2, EMC3, ME2, LOC100130698, KANK4, ARRB2, NLE1, MOS, RIT1, KRT39, CCR3, CORO6, UBE2G2, LOC79999, MAP2K7, LOC644794, PIK3R2, TRIM54, PREX2, LAT2, AGBL3, ANO7, XKR8, MNDA, ABHD11-AS1, LINC01564, STEAP3, TRIM58, PINLYP, TMEM143, TLX2, UTF1, RGS3, MXD1, TMPO-AS1, XLOC_l2_010558, TPM2, RGS16, CNNM2, NR6A1, NXF3, OSBPL6, SFN, BCL3, KIR3DL2, CHST13, NUDT8, LINC01000, MICALCL, NTAN1, GZMH, LINC00152, SSUH2, CTU2, HBZ, CLEC1B, NID2, LOC100129434, C5AR1, MFSD2B, ACSM5, LIN7A, RAB11FIP1, LINC00574, NAT8B, FRAT2, TBL1X, LOC339803, TMEM74B, LOC101059906, KRT13, MUC8, SELL, GYPE, NOXA1, LINC00632, TBL1Y, NCCRP1, LITAF, LOC100130913, LINC00689, RXFP3, TNFRSF1A, MYL4, LOC101927497, NASP, MATK, CCDC166, KIAA1841, PROB1, CAT, CPXM1, NKAPL, SPATA25, IL1B, JADE3, TBPL1, TST, CD37, DMTN, THBD, AIM1L, ENTPD1, AGT, FOXC1, TNNI3, STK11, CACNA1C, SCGB1A1, KATNB1, F13A1, DPY19L3, KEL, LINC01574, S100A9, NPHS2, CCL16, CHPT1, OR2AG2, OR10A5, LINC00884, TMPRSS6, DNAJA4, SCGB3A1, LTB, ABCD4, LRRC4, ARHGEF3-AS1, LECT1, LILRB1, YIPF2, SOCS2-AS1, CCDC176, SEZ6L2, GMIP, CTNNAL1, SYNPO, STX17, ASCC2, GPS2, ZBTB44, PAPL, FAM178B, VTI1B, KANK2, ESRRB, PON3, ARHGAP17, TMEM56, LOC100129455, ALDH3A1, RLBP1, IL9R, BMP1, MSRB1, TNNC2, CXCR1, UNC5A, CLCC1, PAXIP1-AS2, FAM181B, GUCY2GP, F10, TAS2R31, SDPR, ZNF646, C8G, HOPX, GLP2R, WDR90, ADCYAP1R1, APTR, TSACC, CNGB1, C19orf81, RETNLB, PSTPIP1, GOLGA2P6, ASB10, SBK2, POLR2H, lnc- VTI1A-2, EPN2, ITGAL, GIMAP4, TUBA4A, PLA2G6, ADAM8, SRI, TRANK1, HOXA9, APOLD1, APLN, SYT3, HSPB6, PCDHGA8, CYB5R3, SLC14A1, GLUL, RNF216P1, YPEL4, SLC22A4, GRIN2B, LOC645195, C1orf162, LOC100130463, LALBA, MARK3, CCL4L2, BPI, RNF11, GSN, MGC72080, BMP6, MPST, IGLV1-44, RGS18, PYCRL, FADS2, TREM1, SNX32, INPP5K, C21orf58, NKX6-3, PKMYT1, LIF, PINK1, XKR9, ATP9A, MLH3, KRT8, CPN1, S1PR4, AMOTL1, LINC01251, ADH1C, MMP2, FCER1G, TEAD3, SYCP1, CYP21A2, ZNF843, IL2RB, WNT10B, KRT8P12, MEGF11, YY1AP1, SMAP2, LOC101928714, PCDHA7, PCP4, AURKA, VSTM1, CST7, GID4, TTC39A, ST13, TP53I13, WNT3A, PDGFA, SOX6, RNF14, lnc-RP11-1105G2.3.1-3, MICAL2, ZDHHC18, MRVI1, LOC729218, MYO9B, HIST1H3H, HMGCL, NDUFB2-AS1, PRM1, NPAS2, CHIA, GRB7, LTBP4, CLIC3, LOC286087, PDE2A, MCOLN3, LOC729870, PLA2G2A, LOC100133331, CYTH4, SRRD, LOC729159, HLA-DRB4, KCTD11, LOC102723843, GNRH2, LOC285191, PALM3, LINC01539, RNU2-1, ASGR1, RGL4, FAM117A, GSTA2, RILP, LOC101927085, CMTM7, CHST4, TMEM40, CTNND2, CAPN5, ATP2B3, FAM189B, SH2D3C, CCDC134, PRAM1, AIDA, PTH2, PARD3, lnc-SLC35A5- 1, LGMN, KRT15, AHSG, CR1L, XLOC_l2_000001, ABCG5, EPB41, MOK, COX6A2, CCDC154, LINC00951, CRTC1, ZNF157, DCUN1D1, LINC00865, STIL, lnc-RNF39-4, FUBP3, IL17RE, LINC00883, ENDOV, RNF212, ITPKA, TMCC2, LOC100128364, CCNB1, IL10RA, NT5M, CYP4F8, GIMAP6, GEMIN2, SNORA10, MIOX, UBE2Q2P1, SLC15A3, WIPI2, IFT172, UIMC1, SIRPG, TPO, PRSS3P2, CD40LG, SLPI, KRTAP5-10, XK, LOC100132874, CXCR3, ZGLP1, ZNF385A, XIST, LINC00930, ACTA1, CDA, lnc-MACC1-1, HN1, CLCN1, FAM65C, IL6R, FAM188A, CHAF1A, IGFBPL1, ZNF497, E2F2, LY6G6F, COL5A1, C19orf44, MROH7, TMEM262, FRMD1, C1orf86, NETO1, FAM195A, HBG1, SRPK3, ITGA11, NCF1, PQBP1, DEGS2, ATP6V0B, EXD3, IQGAP3, ITGB4, TRPC2, LYN, IRX4, PSPN, HES2, CDC20, GABARAPL2, GTF3C5, MBOAT7, SSC4D, P2RY4, UBE2D1, C6orf106, lnc-GCNT3-1, WDR48, UVSSA, LINC01478, PTPN6, TBXA2R, LOC728975, SERPINF2, MIR646HG, PIP4K2A, LINC01310, LINC01088, DPEP3, lnc- MAB21L2-1, PGLYRP1, MME, MIA, HMHB1, BIRC2, ST6GALNAC4, SCAMP4, OR5H1, SZT2, ACP1, SLC11A1, RIMBP2, CLDN5, TAAR2, C11orf68, TNFRSF12A, OR6K2, DHTKD1, TMOD1, GSTM4, LCE6A, HGD, FAM46C, PDE4A, PSMF1, FAM25C, CCDC183-AS1, TSEN54, TTC25, CRHR1-IT1, PITX1, LINC01160, RNASE1, BMP2K, HBBP1, GPR176, ANAPC1, KRTAP10-10, RRNAD1, SLC6A17, TAL1, CCHCR1, CORO2B, TMEM217, EYS, SEC14L3, CHODL, CHST5, lnc-BRD3-1, MPZL3, ITIH6, KLHL29, PLLP, SLC45A4, TUBA8, GPR146, CDKN2D, GALNT16, DSC2, DRP2, FARP1, XCL1, KIF9-AS1, HOXC6, RAE1, RELL2, NPIPB15, LIMK2, SEMA4D, ANKRD32, MIR503HG, SRC, SSH2, lnc-PROC-2, XLOC_l2_001273, DNAH10, ESPN, LY6G6D, PHF21A, DZIP1, ITSN1, INA, FBXL4, HLA-DQA2, RTN2, ECSIT, TCEANC, PAX7, CLDN19, MUC3A, FAM171A2, NFX1, YBX2, TFE3, ATP2B2, SCARNA17, MT3, DUSP15, CXCL16, ANKRD20A1, MARC2, PHACTR4, CLIC2, SLITRK6, RABGAP1, CLPSL2, APBB2, XLOC_l2_013415, PDE1A, NKIRAS2, ASCL5, TPGS2, HOXA5, EFHD2, CHADL, ICA1, FLJ44511, CHAT, DCAF10, SLC35C1, DMKN, MST1R, IGSF9B, SEMA3B, ORM2, AQP5, C8orf58, RIMS4, SPRY4, GNAO1, C9orf40, MAFIP, BAI1, NRSN2, TNFRSF11B, FBXO22-AS1, FOXD1, YTHDF1, CAMK2N2, DDX11L2, FSD1L, GRHL2, KIR2DS2, lnc-GDF10-2, TLDC1, C9orf116, SMIM2-AS1, MADCAM1, LINC00398, LOC101927766, CAMSAP1, LOC153811, SCGB1B2P, THRAP3, RASSF2, LRRC3C, RFPL4AL1, LOC100128770, ASIC4, TUBB2A, UAP1L1, IGSF21, CDK3, SMIM24, DAPK2, CCDC172, AK8, YBX1, CD55, PLTP, ANKRD54, CYP11A1, RMDN3, SFRP2, ROBO4, FAM69B, CMTM5, TMPRSS9, lnc-EGLN1-1, FAM214B, HBE1, SCARNA12, TANK, RAPSN, SPHK1, RTBDN, CAMP, TMEM37, ZNF771, NFIC, HIST1H2BK, RPPH1, POU3F1, ALPP, LOC101929475, GLRX5, PAK4, BAG6, TLK2, PLXNB3, PNPO, LOC101930506, LDB1, CLK3, CSF3R, DST, RAB13, NPPB, SIX5, TTYH1, C8orf31, YJEFN3, EGFL7, LRCH3, ADRB2, HIF3A, TECPR2, PLEKHG3, ICAM5, LOC374890, LOC100130285, TXNRD2, LEAP2, KC6, KGFLP2, lnc-CCDC71L-1, PYY2, UCP3, CCDC3, MXRA7, ACTA2-AS1, BCS1L, lnc-EPHA1-1, GDE1, TCAF1, ANGPT1, NELL1, LINC00346, SFXN4, STARD10, lnc-MYO10-1, LINC00239, RNF208, PACSIN3, KIFC3, C9orf89, LOC100128219, GPR68, PTGFR, MRGPRG, PRAF2, MST152, BSG, GAS2L1P2, SPRY1, GGT7, HEPACAM2, FAM160A2, GYG2P1, SLC44A2, PTK2B, AMICA1, MGLL, GON4L, ZFAND5, GPBAR1, KRT85, SNORA60, SNAP91, UBE2V1, lnc-ERP44-3, KLRC4, SOX3, lnc-CARHSP1-1, LINC01298, MAP2K3, MLXIP, FLJ44477, SIGLEC10, CCDC96, EMR3, LOC729173, G6PC3, lnc-AC069257.9.1-4, MYCNOS, lnc-CTTNBP2-1, DMWD, DEFB124, lnc- AC136604.1-1, H1F0, TAAR5, TBX1, ZSCAN12P1, PPDPF, PARK2, SLURP1, CDH3, TEX13B, HAMP, PRDM11, LOC100132207, lnc-RASSF7-1, ZNF814, LOC100130654, PRKAR2B, FAM89B, MFNG, ITIH3, MYLK, BRD3, TRIM10, MARK4, FAM180B, TMEM63B, CR1, CHTOP, LOC202181, LOC84214, OSR2, HIST1H2AC, ARHGEF10, TMEM176A, LOC100132481, POU5F1, MMP15, MYH14, FOXK2, CCDC92, POT1, GSX1, LOC728254, RCOR3, GPR18, KIR3DX1, BIN3-IT1, MPDU1, HLA-F, SPP1, LTBP1, ADRA1A, PRSS1, DOK2, HERC2P10, MMP17, LOC728673, LRRC42, IFIT1B, OXT, APOC1, HHIP-AS1, MAMDC4, FAM53C, ITGB3, TSTA3, OPN4, TOMM20L, DGKQ, DENND3, CD164L2, AQP7P1, CYP17A1, C10orf82, NUAK2, PPL, STXBP5L, MOSPD1, LINC00954, CDHR2, GFI1B, STARD5, LOC401557, SSX2IP, LINC01133, SIAH2, PCSK4, BBC3, MAU2, OR6M1, MAG, ADM, GCM1, DYTN, NCR3, SPDEF, LAMC2, AKIRIN1, ASF1B, CCDC108, CCDC57, C5AR2, SIPA1L1, HYAL3, ZFYVE19, GNG12-AS1, LOC400043, lnc-ZADH2-1, lnc-FBRSL1-4, PKD1, LOC100506036, SAMD10, PPM1D, RPH3A, PLA2G2C, NYNRIN, CAMKK1, ALPL, PROK2, SLC28A1, SETD1B, DYRK3, TSPAN4, AGAP2-AS1, CD300LF, EGLN1, MIER1, WNK1, LYNX1, FLJ30064, RUSC2, CACNA2D2, KIAA0040, MOCOS, C9orf69, RGS2, HBM, FER1L6-AS2, RAB27B, LILRA2, C3orf22, BRSK2, CBFA2T2, SLC22A17, ST3GAL2, KCNJ15, ZFPM1, LOC400927-CSNK1E, KIFC2, lnc-TMEM178-1, EFNA2, TOP3A, TRIM14, PPP1R13L, HOTAIR, RARRES3, DAB2IP, FOXF1, lnc-CRIPAK-1, ZBTB20, SPATA20, ERI1, LINC01089, DUSP9, TBC1D3P5, FOXN1, CXCL8, ZFAND4, EFNB2, EXTL3, HSPA6, LOC730183, F2RL3, KRTAP4-3, ARHGEF28, GAGE7, SUSD2, CSNK1D, LHX6, XLOC_l2_001592, SIGLEC15, SF3A2, LOC729737, CACNG6, SSU72, RAB3D, KLK2, LOC102724279, PLA2G15, HNRNPUL1, TRPV5, OXER1, LOC100131131, LOC100996924, lnc-C6orf221-1, LOC285095, CLRN1-AS1, SLC12A3, NAMPT, MEIS1, RBFOX3, MAP7D2, MNT, GSK3A, AKAP4, LOC113230, KLK6, SH3GL1P1, MMD, PVR, NRG4, PTGIR, RGCC, DESI1, NRIP3, SPATA1, SLC7A14, ZNF267, PAK1, GOLGA7, HOTS, PEG10, KRT81, MTVR2, HMGA2, LOC284513, LINC00861, CSAG4, ZSWIM7, RTN4RL2, LINC00176, CXXC4, ERBB3, XCR1, SLC38A7, PAEP, SEMA4B, lnc-SNURF-3, UBE2I, PALD1, C1orf177, AATK, TGIF1, OSBPL2, lnc-C4orf42-3, SRRM2-AS1, OLFML2A, DISP2, CTSL, FBN2, G0S2, ANKRD36BP2, GP9, ADRA2C, IL1RAP, LINC00162, DNAJB2, SPOCD1, DHRS13, TMEM61, CASP14, PALM, TBL1XR1, SGCD, RNF123, NPY, EMR2, PHLDB1, MIR100HG, BCL2L11, ARHGEF39, C11orf86, KRT23, HYAL2, TUBB4A, DYNLL2, lnc-AF131215.3.1-1, PCDH19, TBX21, C2orf82, AGXT, FN3K, RPL13AP17, C2orf50, NOA1, CD79B, ATF6B, CPT1C, CTD-3080P12.3, LINGO2, RDH16, ZNF394, FIS1, ZNF445, TLR4, SYCE1L, ODC1, SLC22A18, SP7, MMRN2, BRAF, ABHD1, MAGEA12, HLA-DPB1, NR5A2, TP73, ARAP3, SSX2, FAM109A, C1orf158, LEPR, BET1, EPS15L1, SNORD17, VMO1, HIST1H2AD, ARHGAP44, NDUFV3, PLXDC2, C3, ENDOG, CCDC18, ABCC3, SIRPA, CTDSPL, CASP5, ASB18, YOD1, GALNT1, CENPP, H1FNT, WDR26, C1orf194, BLOC1S1, C15orf59, SNAI2, F8A2, INPPL1, DIS3L, GAN, HEPH, FMNL2, PACSIN2, CELF3, GPX1, ALDH5A1, CTDSP1, JMJD7-PLA2G4B, MAP6, BET1L, TM4SF1, STEAP4, CCDC182, CD48, FBXO36, PCOLCE, STX1A, LOC401286, ACKR1, LINC00665, FCN3, NOS3, NCAPD3, PANX3, PHF12, C8orf60, BEND3, LIME1, SMPDL3B, RNF175, DDX31, ENGASE, SLC25A28, LINC00925, ITGB5, GALNT10, NFIA, UBE2F, MOG, TUBA3D, MMP9, MOB1B, ESPL1, SLA, RGS11, GNAZ, NFXL1, TFR2, DNAJC4, BMPR1A, HDAC8, TONSL, CSAG1, SAMD4A, DUSP13, OSER1, KRTAP5-7, CTBS, PLEKHG5, HES6, LINC01554, VPS9D1-AS1, MGP, PBX1, RNASET2, CYP4F3, MTMR9LP, TGFA, LRRIQ3, C16orf59, LRRC75A, SPTB, PDE1C, C1orf186, LTB4R2, COL28A1, TUBB8, DHRS2, LINC01233, RXRB, LOC729451, CA8, MBOAT2, B9D2, BCORL1, MAP3K7CL, FLJ37786, SLC34A3, LGALS3BP, SH2B2, LGALS3, NAPA, WIPF1, MARCH9, TMEM88, PPP1R11, SUSD6, PGM5, TINAGL1, FPR2, CLEC4E, IGSF1, PGLYRP2, N4BP1, TBCEL, LINC01375, VIL1, LOC102725171, IGF2, LOC646513, RHOBTB1, GOLGA8IP, CA4, SLC25A26, CBX2, CD34, PIP5K1B, C11orf71, SECTM1, TMEM191B, ICAM1, HCST, FEZ1, MAPK8IP1, TMEM191A, YIPF6, SLC6A18, FOXA3, LOC101927686, CCDC61, CXADR, HLA-DPA1, ALPI, SP2, C9orf106, GPR3, ZMAT2, LOC286382, C19orf12, ACTL8, GNG8, ILVBL, MTSS1L, lnc-PABPC4-2, VPS9D1, MAPKAPK2, C4B, MYOF, HTR7P1, NLRX1, KRTAP5-11, WASH1, SYDE1, DPF1, KCP, CXCR5, RELT, ANKRD18B, TNAP, JARID2, ZNF746, SPNS3, PLXNC1, PLCL2, OPRD1, ADAM23, SLC29A1, HAND1, WBP2, LOC100130938, RNASE13, SLC5A10, RSRC1, VSIG10, CNPY1, IGSF6, OPN1SW, NR0B2, LOC101927507, ENO3, CEACAM3, ALDH1B1, MAOA, SLC37A4, LINC00354, FOS, SERP2, PRKCDBP, ASPHD1, PLCH2, KRT4, ADAMTS7P1, USP33, DFFA, AGRN, KLRG2, LOC101929709, DIO2, GAL, MAP4K5, PKLR, SNCB, OR8G2, LOC100996573, CXCL1, S100A5, TMEM158, C6orf25, REPS2, MAP7, C1orf52, LPPR2, GSTO2, CDK8, ULK1, CRAT, ART5, ND1, lnc-SLC38A8-1, CLDN7, LINC01121, ITLN1, LINC01061, OSCP1, ESPNL, ZIC4, PRLH, SDHAF1, AZGP1, CHI3L1, LOC100131864, GDNF, EEF1A2, HIST1H2BM, RNFT2, LY6G6E, LINC01512, PRKAG3, C19orf80, EXOC3L1, PPP1R3B, ITGB2, LRRC25, WWOX, HLA-DQA1, ARMC5, DLG5, MAP3K13, TPM1, PTPRF, MBD3, CECR1, VEGFA, NKAIN4, LOC100996579, FAM131C, MED18, EIF1B, TRO, FOXO4, ITLN2, OR4F15, MAGEE1, SFXN5, NRBF2, RUNDC3A, RPL23AP32, ALOX12, PLD1, EHD1, OPTN, CASZ1, FLCN, LOC100133299, SPEM1, SLC25A44, PGP, PGF, ATF3, LOC100129112, SLC10A3, REM2, RBM14, GLIPR2, RFESD, GFRA1, CYC1, HRASLS5, LMX1B, RER1, UBTD1, EXOC3-AS1, LOC284219, AKT1S1, ADM2, SYT2, TFF3, ABCC2, PNO1, STX2, LOC102723701, MRGPRF, TLCD1, STRA6, CHAC1, LOC101927910, HLA-DRB1, DYRK1B, LOC645645, ZFP36, RBP7, lnc-GABRE-1, HSD17B1, KRTAP13-4, YIPF1, GNG11, ELOVL5, CD177, lnc-WDR7-8, lnc-DIO2-3, IL18RAP, SBNO2, DNTTIP1, DIAPH3, VWA5A, USP54, TSHB, MGAM, CCDC33, DLK1, TCEA1, GALNT14, AKR1C3, PTDSS2, PCGF2, RIOK3, EVI2A, TMTC1, MED22, BTN2A3P, PTGDS, PDE5A, SLC38A5, GATA2, CD79A, ACAP3, LDB3, OR4A15, CLEC4A, CYP2A13, HAPLN2, ZNF185, ZC3HAV1L, SH2D2A, TMEM95, CLEC4M, BCL2A1, TENM1, GPR62, ICAM3, PPIF, GMEB2, DNAAF5, DPH3P1, KLK1, PYGL, SIRT3, CTAG2, GPX5, MGARP, SH2D1B, HPX-2, POLE2, ENKD1, ARHGAP35, CLDN6, CDC14B, FASLG, TNFRSF8, HK3, ZNF713, IL5RA, A4GALT, HOXD9, NUP98, KCNH3, NME4, FAM57B, PAX4, FAM157A, ND5, EPB41L4A, TMEM71, LYL1, TTC5, CYP17A1-AS1, BRF1, TMEM43, C19orf38, PTPLA, PTHLH, USP32, ANKRD13D, PLVAP, CYBRD1, MAPK1, SLC6A19, NMUR1, WWC3, FMN1, TBC1D3L, EFEMP2, CAV1, IGFBP3, KCNK12, PNPLA2, SOX13, CTTN, ADAMTSL1, NXF5, TCP10L, DEF8, KCNK1, ABCG2, KRT18, OAZ2, TMEM120A, OR3A3, GPATCH1, UCK2, F8, OR3A4P, LOC100129215, WDR62, LRP5L, KRTAP19-8, PSMG3, ATF6, STX5, LOC100288069, PCDHB2, COX1, HOXB9, ORM1, NAGS, TOPORS-AS1 PLA2G4A, PSMA1, TMTC2, ERP44, FAM13A, COL8A2, DACT1, EME2, PTX3, ZWINT, ANKRD50, KIAA0556, PLXNB2, CEACAM7, OAF, PFKFB2, MPP7, AZU1, FSTL3, SUOX, NLN, PPARGC1B, OCRL, TCN2, FMO5, SLC24A1, CTSG, LINC00482, FGD6, Normal-like SCPEP1, LOC100270804, MTHFSD, SRGAP2C, GPR68, SERPING1, BCAR1, GPR78, HMGB4, STARD7-AS1, SNORD15A, GZMA, NOC4L, XCL1, FOXO6, LINC00029, MGAT3, CXCR3, LOC101927139, PROSER3, SLC5A2, ADRB2, LOC646626, KCNH4, ASPSCR1, SLC22A8, SLC35E2B, CCDC7, TTI1, SMIM5, SCARNA6, LOC644277, NES, POMGNT1, LIPE, ERN1, SLAMF7, ALX4, POLR2J4, SPTBN4, PARD6G-AS1, LOC221814, MUC5AC, PORCN, CD8A, KLKB1, ZNF235, LYPLA2, LINC00523, LINC00964, LAG3, ADAMTSL2, LTA, PCDHA5, NBPF6, ACOT11, TMEM145, PPP6R2, LINC00870, CHRND, FMO6P, CXCL12, PABPN1L, P2RY6, lnc-CHST4-3, MON2, SELK, TLR8, PNLIPRP1, CXCR5, HMX2, OLFML2B, COL4A4, CARHSP1, SNED1, KCTD2, ANKFY1, FAM180A, GPR15, HMG20B, SNORD17, ACER2, DRD3, TXNL1, FAM20C, EWSAT1, LINC00311, RMRP, ATP2B2, PCDHGA7, MCAT, GOLGA2P7, SMCR2, MMP25-AS1, PSD, LOC340357, LOC389273, RUNX3, WASH5P, TTTY16, ZNF664-FAM101A, C12orf75, FBRS, SLC10A3, VASH1, TBX21, LOC148696, TINAGL1, APOBEC3A, LOC100130920, NYX, HIST1H3H, TARP, WDR93, XLOC_l2_009886, LOC100127940, GDF7, TMEM171, MROH1, KCNH2, NPC1L1, ADORA1, LOC101928978, GZMB, GFRA3, KLF14, OR1S2, HCAR3, SYTL2, KAT6B, POU2F2, FAM129A, UCKL1, SCML4, LOC100133286, SNORA71C, SEMA7A, NPPA, LCE1D, SLC6A5, lnc-AF131215.3.1-1, KCNQ3, FAM66D, LGR6, RPL39, GTF3C5, MOCS3, XLOC_l2_001961, NAT10, LOC100507403, FAM65A, LAMA3, CNTNAP1, OR51I2, IRF2BPL, CD300A, HAPLN2, LINC01104, ROBO3, MYBL1, LOC101928991, USP17L2, ZNF488, ETNK2, LINC01182, IRAK1, KCNK15, FLJ42393, OR9A2, FAM66A, TRIM71, CACNA2D2, ALKBH5, CEP57L1, LINC01126, ATP6V1G2, C19orf25, FAM219A, lnc-RP11-389E17.1.1-1, IL2RB, UCP3, RARA, GRIN2C, PRRC2B, STIL, lnc-TP53INP1-1, TLX2, TMEM221, ZIC5, FBXO15, STC1, SHANK1, SAMD11, DNHD1, SLC34A1, SSBP3, KRT73, KRT33A, ACR, LIN9, OR10H2, CSNK1G2, IGF2-AS, CDC27, SLC22A10, GNG10, PIK3CD, SLC35D2, EPHB2, LOC102724484, SLC25A47, WDR18, ABCC4, LOC100289580, AKT3, PCDH19, GIPR, lnc-RTL1-2, PRR5, LOC101929696, GPR88, SH2D2A, LINC00865, SLC22A11, KIRREL3, OR2M7, REREP3, IGLV1-44, FUT11, TFDP2, KCNH5, lnc-CTH-4, MPP1, LOC101927043, LRRC37A5P, LYAR, LOC646743, MAGED4B, MDGA1, DPM3, ZACN, CCDC167, SCGB2B2, CTRC, LINC00494, AKAP5, LY96, PAGE2B, GRB14, KRTAP10-12, DSCR8, NEGR1, VWCE, TNNI1, MOGS, ZNF562, GYPA, lnc-DYM-1, AK8, SALL3, TSTD1, DLEU7, MIR22HG, RRP7B, PFDN5, PIPOX, lnc-USP35-3, RNH1, CRLF2, ZNF418, PGA4, LINC00659, PRSS33, BPGM, KIAA1841, FCRL6, SLC6A17, GABRP, C1orf64, NUDT10, DEFA3, MOK, RPL3L, CCDC129, LINC01564, METRNL, CDX1, R3HDML, DNAL4, PRDM13, LOC101929494, NAALADL2, LINC00969, CCR10, HLA-L, LINC00630, SOAT2, P2RX2, KRT86, LINC01186, PMS1, JRK, SREBF1, SHD, CLC, CRYAA, LOC100129447, FLJ41170, SLC25A3P1, LOC100132356, C17orf53, TERC, LOC100129534, RBM38, LINC01529, UTS2, LINC00574, G3BP1, SPDYC, CDC34, LOC645427, IPO11, B3GALT5-AS1, DUXA, A1BG, PPIL2, SMIM2-AS1, LINC00687, GPRC5D, EPS8L3, SRXN1, PKD1, LOC648987

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

Supplemental Table S8 – Significant genes and pathways for longitudinal analysis.

Functional term Total genes 8 mo 14 mo 20/26 mo 38 mo 48/54 mo adaptive immune 785 85 77 32 33 63 system MRC2,SLAMF7,PSMA4,AP2S1,CYBA,FCGR2B,UBE2A,DYNLL1,L ITGAL,CD79B,CD22,CD74,SLAMF7,FCGR2B CD22,PSMC4,CD7 CD22,CD74,SLAMF MAP3K14,FYN,CD22,PSMC4,CD7 AG3,CD209,BLNK,NCR2,AP1B1,PSMA6,PSME2,CD40,KLC3,AKT2, ,UBE2A,RAPGEF3,ANAPC5,LAG3,CD200,BL 4,SLAMF7,LAG3, 7,LAG3,CD200,BLN 4,SLAMF7,LNX1,FCGR2B,LAG3, CD79A,MAP3K8,PSMD3,CD81,PSMD9,CD86,CBLB,FBXO6,CDC20, NK,NCR2,CD40,NFKBIB,KLC3,AKT2,CD79A CD200,BLNK,CD4 K,AKT2,CD79A,NP CD200,BLNK,NCR2,CD40,KIF3B, BTN1A1,PSMF1,HECTD3,CANX,MKRN1,KLRC1,BLK,KIF11,CENP ,SIGLEC5,NPDC1,MAP3K8,PSMD3,CTSC,PS 0,AKT2,CD79A,N DC1,CBLB,PTPN22, HERC1,AKT2,CD79A,PPP2R1A,N E,AKT1,KIF2C,FBXO10,UBC,RASGRP3,CD8A,TRIP12,CD1A,CD1C MD14,FBXO6,MAPKAP1,BTN1A1,PSMF1,H PDC1,CD81,BLK, BLK,KLRG1,RPS27 PDC1,FBXL15,MAP3K8,NFKB1,B ,ICOSLG,SHC1,AP2M1,ASB16,RACGAP1,SLAMF6,KBTBD8,KIF15, ECTD3,KLRC1,BLK,DCTN3,KIF11,CENPE,K DCTN3,KLRG1,R A,ASB10,RASGRP3 TN1A1,PSMF1,HECTD3,LRRC41, FBXW12,RNF123,CTSB,CYBB,LAIR2,KIR3DL1,INPP5D,SIGLEC7, LRG1,AKT1,FBXO10,KLRF1,SEC24D,AP1S3, ASGRP3,CD8A,C ,CD8A,ICOSLG,CD PTPN22,BLK,DCTN3,SEC31A,PPP adaptive immune UBB,CD34,UBE2O,MEX3C,CD19,CALR,SIAH2,UBE2E2,SOCS1,PR RASGRP3,CD8A,CD1A,CD1C,ICOSLG,SHC1, D1A,CD1C,ICOSL 8B,CD34,CD19,CAL 3CA,KLRG1,AKT1,ASB10,SEC24 785 system R5,LILRB4,PDCD1,NCR1,CTSE,PLCG2,SH2D1B,HLA-DOA,HLA- ASB16,SLAMF6,KIF15,FBXW12,RNF123,PR G,SLAMF6,KBTB R,HLA- D,ITPR1,RASGRP3,CD8A,ICOSLG DMA,TRIM71,KLRK1,IFI30,HLA-DPB1,HLA-DQB2,HLA-DOB KCB,LAIR2,KIR3DL1,SIGLEC7,CD34,UBE2 D8,CD8B,CD34,C DQB1,PDCD1,ASB ,SHC1,REL,FBXW12,CTSB,KIR3D O,CD19,HLA- D19,SOCS1,PDCD 13,SH2D1B,HLA- L1,KCTD6,CD34,CD19,CD300LB, DQB1,UBE2F,SOCS1,PRR5,PDCD1,NCR1,CT 1,HLA-DOA,HLA- DOA,HLA- CALR,PRR5,PDCD1,KIR2DL4,AS SE,CARD11,SH2D1B,HLA-DOA,HLA- DMA,KLRK1,HL DMA,NCR3,KLRK1 B13,SRC,HLA-DOA,HLA- DMA,NCR3,IGLV1-44,SIPA1,KLRK1,HLA- A-DOB,ORAI1 ,HLA-DPA1,HLA- DMA,IGLV1- DPB1,HLA-DQB2,HLA-DOB,MRC1 DQB2,HLA-DOB 44,SIPA1,KLRK1,HLA- DQB2,HLA -DOB,RNF115,ORAI1

adaptive immune Functional term system

Total genes 785

MRC2,SLAMF7,PSMA4,AP2S1,CYBA,FCGR2B,UBE2A,DYNLL1,L AG3,CD209,BLNK,NCR2,AP1B1,PSMA6,PSME2,CD40,KLC3,AKT2, CD79A,MAP3K8,PSMD3,CD81,PSMD9,CD86,CBLB,FBXO6,CDC20, BTN1A1,PSMF1,HECTD3,CANX,MKRN1,KLRC1,BLK,KIF11,CENP E,AKT1,KIF2C,FBXO10,UBC,RASGRP3,CD8A,TRIP12,CD1A,CD1C 8 mo 85 ,ICOSLG,SHC1,AP2M1,ASB16,RACGAP1,SLAMF6,KBTBD8,KIF15, FBXW12,RNF123,CTSB,CYBB,LAIR2,KIR3DL1,INPP5D,SIGLEC7, UBB,CD34,UBE2O,MEX3C,CD19,CALR,SIAH2,UBE2E2,SOCS1,PR R5,LILRB4,PDCD1,NCR1,CTSE,PLCG2,SH2D1B,HLA-DOA,HLA- DMA,TRIM71,KLRK1,IFI30,HLA-DPB1,HLA-DQB2,HLA-DOB ITGAL,CD79B,CD22,CD74,SLAMF7,FCGR2B,UBE2A,RAPGEF3,AN APC5,LAG3,CD200,BLNK,NCR2,CD40,NFKBIB,KLC3,AKT2,CD79 A,SIGLEC5,NPDC1,MAP3K8,PSMD3,CTSC,PSMD14,FBXO6,MAPK AP1,BTN1A1,PSMF1,HECTD3,KLRC1,BLK,DCTN3,KIF11,CENPE, KLRG1,AKT1,FBXO10,KLRF1,SEC24D,AP1S3,RASGRP3,CD8A,CD 14 mo 77 1A,CD1C,ICOSLG,SHC1,ASB16,SLAMF6,KIF15,FBXW12,RNF123,P RKCB,LAIR2,KIR3DL1,SIGLEC7,CD34,UBE2O,CD19,HLA- DQB1,UBE2F,SOCS1,PRR5,PDCD1,NCR1,CTSE,CARD11,SH2D1B, HLA-DOA,HLA-DMA,NCR3,IGLV1-44,SIPA1,KLRK1,HLA- DPB1,HLA-DQB2,HLA-DOB,MRC1 CD22,PSMC4,CD74,SLAMF7,LAG3,CD200,BLNK,CD40,AKT2,CD7 9A,NPDC1,CD81,BLK,DCTN3,KLRG1,RASGRP3,CD8A,CD1A,CD1 20/26 mo 32 C,ICOSLG,SLAMF6,KBTBD8,CD8B,CD34,CD19,SOCS1,PDCD1,HL A-DOA,HLA-DMA,KLRK1,HLA-DOB,ORAI1 CD22,CD74,SLAMF7,LAG3,CD200,BLNK,AKT2,CD79A,NPDC1,CB LB,PTPN22,BLK,KLRG1,RPS27A,ASB10,RASGRP3,CD8A,ICOSLG, 38 mo 33 CD8B,CD34,CD19,CALR,HLA-DQB1,PDCD1,ASB13,SH2D1B,HLA- DOA,HLA-DMA,NCR3,KLRK1,HLA-DPA1,HLA-DQB2,HLA-DOB MAP3K14,FYN,CD22,PSMC4,CD74,SLAMF7,LNX1,FCGR2B,LAG3, CD200,BLNK,NCR2,CD40,KIF3B,HERC1,AKT2,CD79A,PPP2R1A,N PDC1,FBXL15,MAP3K8,NFKB1,BTN1A1,PSMF1,HECTD3,LRRC41, PTPN22,BLK,DCTN3,SEC31A,PPP3CA,KLRG1,AKT1,ASB10,SEC24 48/54 mo 63 D,ITPR1,RASGRP3,CD8A,ICOSLG,SHC1,REL,FBXW12,CTSB,KIR3 DL1,KCTD6,CD34,CD19,CD300LB,CALR,PRR5,PDCD1,KIR2DL4,A SB13,SRC,HLA-DOA,HLA-DMA,IGLV1-44,SIPA1,KLRK1,HLA- DQB2,HLA-DOB,RNF115,ORAI1

Franks JM, et al. Ann Rheum Dis 2020;0:1–8. doi: 10.1136/annrheumdis-2020-217033