Table S1. Patient characteristics of the validation set AB0i (n = 18) HLAi (n = 9) P Type of donor, n (deceased, living) 0/18 9/0 < 0.001 Retransplantation, n (1st/2nd/ 3rd) 18/0/0 2/5/2/0 < 0.001 Recipient age, years 47 [24;68] 45 [21;78] 0.817 Recipient sex, male, n 11 8 0.757 Donor age, years 45 [25;74] 46 [23;60] 0.872 Donor sex, male, n 8 3 0.692 Peak PRA 0 [0;92] 50 [0;96] 0.012 HLA mismatch 3 [2;6] 4[2;5] 0.170 Dialysis vintage (months) 5.5 [0;62] 46.8 [4;92.4] 0.008 Cold ischemia, hours 0.6 [0;2.3] 17.4 [9;21.6] < 0.001 Antibodies before transplantation Hemagglutinins, titers 1:16 [1:2;1:128] DSA class I, n 0 5 0 DSA class I, MFI 2000 [0;15300] DSA class II, n 1 3 0 DSA class II, MFI 2000 950 [0;22300] Antibodies after transplantation Hemagglutinins, titers 1:2 [1:1;1:8] DSA class I, n 0 4 DSA class I, MFI 0 [0; 11 800] DSA class II, n 0 3 DSA class II, MFI 0 [0; 5000] Induction treatment < 0.001 Basiliximab, n 16 1 Thymoglobuline, n 2* 8 Serum creatinine at 3 months (µmol/l) 105 [72;146] 138 [88;172] 0.043 Data are presented as n or medians [min; max]. *Two patients from the validation AB0i cohort received rATG induction due to increased risk of rejection (peak PRA 63 %, DSA of 2000 MFI) Table S2. Histological scores of analyzed biopsies in the validation set of patients. Banff score AB0i (n = 18) HLAi (n = 9) P valuep (0/1/2/3) g 14/1/1/0 5/3/0/1 0.124 cg 16/0/0/0 6/1/1/0 0.113 mm 16/0/0/0 9/0/0/0 1 i 16/0/1/0 7/1/0/0 0.176 t 12/2/3/0 5/2/1/0 0.691 ti 13/4/0/0 4/3/1/0 0.116 ci 6/11/0/0 4/4/0/0 0.484 ct 4/13/0/0 1/7/0/0 0.520 v 16/0/0/0 8/0/0/0 0.746 cv 0/12/3/1 1/4/2/0 0.609 ah 3/7/6/1 2/3/3/0 0.886 ptc-s 16/0/1/0 5/3/1/0 0.031 ptc-q 16/1/0/0 5/2/2/0 0.045 ptc-e 16/1/0/0 6/2/1/0 0.151 C4d 0/3/2/12 0/2/1/6 0.961 Table S3. GO terms enriched in controls compared to HLAi or AB0i patients. Genes with higher expression in controls compared either to the AB0i or HLAi group (FC > 2, p < 0.05) were entered into the David gene ontology database. GO terms upregulated in controls compared Count Benjamini p to the AB0i group value GO:0006952 defense response 33 1.44E-06 GO:0009611 response to wounding 28 3.15E-05 GO:0006954 inflammatory response 21 6.98E-05 GO:0006955 immune response 29 2.94E-04 GO:0050778 positive regulation of the immune response 13 7.49E-04 GO:0002684 positive regulation of the immune system 16 1.13E-03 process GO:0002253 activation of the immune response 10 2.94E-03 GO:0002526 acute inflammatory response 10 3.07E-03 GO:0006959 humoral immune response 9 4.50E-03 GO:0006956 complement activation 7 5.26E-03 GO terms upregulated in controls compared Count Benjamini p to the HLAi group value GO:0005578 proteinaceous extracellular matrix 46 7.95E-14 GO:0031012 extracellular matrix 48 1.59E-13 GO:0044420 extracellular matrix part 25 1.37E-10 GO:0005576 extracellular region 123 7.76E-10 GO:0044421 extracellular region part 74 5.70E-09 GO:0005581 collagen 11 1.25E-05 GO:0022610 biological adhesion 54 1.99E-05 GO:0031226 intrinsic to plasma membrane 76 2.73E-05 GO:0007155 cell adhesion 54 3.77E-05 GO:0030198 extracellular matrix organization 18 3.90E-05 GO:0005604 basement membrane 14 9.16E-05 GO:0005887 integral to plasma membrane 72 1.45E-04 GO:0043062 extracellular structure organization 21 2.80E-04 GO:0005201 extracellular matrix structural constituent 15 4.63E-04 GO:0030199 collagen fibril organization 9 1.19E-03 GO:0001501 skeletal system development 29 1.28E-03 GO:0044459 plasma membrane part 109 1.66E-03 GO:0008201 heparin binding 15 2.16E-03 GO:0005539 glycosaminoglycan binding 17 2.42E-03 GO:0030247 polysaccharide binding 18 2.58E-03 GO:0001871 pattern binding 18 2.58E-03 GO:0030934 anchoring collagen 5 5.28E-03 KEGG PATHWAY hsa04512:ECM-receptor interaction 17 1.21E-06 KEGG PATHWAY hsa04510:focal adhesion 21 4.61E-04 GO terms upregulated in the HLAi group Count Benjamini p compared to controls value GO:0055114 oxidation reduction 59 6.92E-05 GO:0048037 cofactor binding 32 2.29E-04 GO:0016054 organic acid catabolic process 20 3.66E-04 GO:0046395 carboxylic acid catabolic process 20 3.66E-04 GO:0006811 ion transport 64 4.53E-04 GO:0000267 cell fraction 81 1.14E-03 GO:0006631 fatty acid metabolic process 26 1.26E-03 GO:0006812 cation transport 49 1.46E-03 GO:0005624 membrane fraction 62 2.31E-03 GO:0016323 basolateral plasma membrane 24 2.43E-03 GO:0009063 cellular amino acid catabolic process 14 2.46E-03 GO:0016324 apical plasma membrane 19 2.60E-03 GO:0050662 coenzyme binding 24 2.73E-03 GO:0005626 insoluble fraction 64 3.04E-03 GO:0045177 apical part of cell 23 3.26E-03 GO:0015293 symporter activity 20 3.89E-03 GO:0055085 transmembrane transport 48 4.22E-03 GO:0006820 anion transport 20 4.79E-03 GO:0005506 iron ion binding 31 5.96E-03 GO:0009055 electron carrier activity 25 7.44E-03 GO:0044271 nitrogen compound biosynthetic process 32 7.83E-03 GO:0009310 amine catabolic process 14 7.92E-03 GO:0006732 coenzyme metabolic process 20 8.12E-03 GO:0009410 response to xenobiotic stimulus 8 8.71E-03 GO:0015695 organic cation transport 8 8.71E-03 KEGG PATHWAY hsa00982:drug metabolism 15 1.53E-04 KEGG PATHWAY hsa00980:metabolism of xenobiotics by 15 2.00E-04 cytochrome P450 KEGG PATHWAY hsa00053:ascorbate and aldarate metabolism 8 5.82E-04 KEGG PATHWAY hsa00480:glutathione metabolism 12 1.31E-03 KEGG PATHWAY hsa00500:starch and sucrose metabolism 10 5.75E-03 KEGG PATHWAY hsa00040:pentose and glucuronate 7 6.17E-03 interconversions *Only GO terms with Benjamini p values < 0.01 are shown. Table S4. Upregulated genes for 3-month protocol C4d-positive biopsies of AB0i compared to HLAi patients. Illumina Array Rank Entrez Gene ID Gene Symbol Fold change P value Address ID 1 5690343 57449 PLEKHG5 6.37 0.0000 2 670068 1571 CYP2E1 6.27 0.0106 3 3400184 137902 PXDNL 6.23 0.0002 4 6550204 84870 RSPO3 5.52 0.0028 5 5550414 56475 RPRM 4.98 0.0009 6 6960561 148808 MFSD4 4.97 0.0004 7 2650382 4626 MYH8 4.87 0.0164 8 2230475 284835 C21orf130 4.74 0.0003 9 4560647 348932 SLC6A18 4.37 0.0482 10 4210719 8092 CART1 4.36 0.0014 11 730563 650263 LOC650263 4.36 0.0047 12 6040020 NA 4.27 0.0019 13 7610196 89792 GAL3ST3 4.17 0.0004 14 2030095 NA 4.16 0.0022 15 770736 338328 GPIHBP1 4.15 0.0003 16 7200328 NA 4.10 0.0020 17 3060273 4504 MT3 3.94 0.0004 18 3440541 728816 LOC728816 3.89 0.0001 19 10131 2911 GRM1 3.88 0.0025 20 380019 115265 DDIT4L 3.78 0.0054 21 7320669 25891 PAMR1 3.72 0.0247 22 5560674 4023 LPL 3.69 0.0017 23 2480427 NA 3.68 0.0001 24 1470053 57221 KIAA1244 3.67 0.0002 25 6590538 7018 TF 3.66 0.0068 26 4760390 83539 CHST9 3.63 0.0015 27 1230477 10265 IRX5 3.63 0.0043 28 4920102 148808 MFSD4 3.54 0.0003 29 4560523 27129 HSPB7 3.53 0.0002 30 4810142 2103 ESRRB 3.49 0.0009 31 1690050 41 ACCN2 3.47 0.0200 32 3360500 1950 EGF 3.46 0.0005 33 6650504 24 ABCA4 3.45 0.0008 34 2680056 1066 CES1 3.41 0.0008 35 4180324 115572 FAM46B 3.40 0.0016 36 6100259 7447 VSNL1 3.39 0.0070 37 360402 273 AMPH 3.39 0.0037 38 6620035 845 CASQ2 3.34 0.0023 39 5360301 55885 LMO3 3.33 0.0011 40 7100722 157724 SLC7A13 3.28 0.0312 41 7610193 26223 FBXL21 3.25 0.0013 42 1690561 10777 ARPP-21 3.24 0.0064 43 5290026 114800 CCDC85A 3.22 0.0015 44 4760040 4703 NEB 3.17 0.0005 45 7650068 349136 WDR86 3.15 0.0025 46 2570746 26153 KIF26A 3.13 0.0000 47 6510403 51557 LGSN 3.13 0.0264 48 6980064 654 BMP6 3.11 0.0059 49 4220592 55799 CACNA2D3 3.11 0.0017 50 6650296 649044 LOC649044 3.08 0.0004 51 5310722 2047 EPHB1 3.06 0.0011 52 6350397 55107 ANO1 3.03 0.0043 53 5810307 130576 LYPD6B 3.02 0.0007 54 5390687 1363 CPE 3.02 0.0020 55 4250301 150244 FLJ31568 3.01 0.0201 56 3190121 130576 LYPD6B 2.99 0.0002 57 5050390 9066 SYT7 2.99 0.0010 58 1740630 2813 GP2 2.97 0.0068 59 3850112 116362 RBP7 2.96 0.0003 60 7000427 5733 PTGER3 2.96 0.0053 61 2340347 23287 AGTPBP1 2.95 0.0020 62 1030286 6523 SLC5A1 2.94 0.0299 63 6650438 9145 SYNGR1 2.93 0.0002 64 2750563 5502 PPP1R1A 2.93 0.0011 65 1070689 202151 RANBP3L 2.92 0.0015 66 2900154 6557 SLC12A1 2.89 0.0053 67 4280739 147495 APCDD1 2.87 0.0209 68 4200754 6484 ST3GAL4 2.85 0.0020 69 780341 83643 CCDC3 2.85 0.0082 70 3440376 2235 FECH 2.85 0.0030 71 5360670 5328 PLAU 2.85 0.0011 72 5390128 55203 LGI2 2.84 0.0141 73 7000433 6344 SCTR 2.84 0.0048 74 4230739 57537 SORCS2 2.84 0.0080 75 6420025 55107 TMEM16A 2.83 0.0032 76 6480433 1288 COL4A6 2.82 0.0013 77 60603 2743 GLRB 2.81 0.0021 78 870575 63876 PKNOX2 2.77 0.0003 79 2100228 1805 DPT 2.73 0.0143 80 5570682 79827 ASAM 2.73 0.0153 81 7100154 783 CACNB2 2.72 0.0002 82 6980543 4004 LMO1 2.71 0.0003 83 5050561 79781 IQCA1 2.69 0.0007 84 3840376 84913 ATOH8 2.69 0.0025 85 3840753 23462 HEY1 2.69 0.0051 86 1660019 9627 SNCAIP 2.68 0.0203 87 2750431 6261 RYR1 2.66 0.0142 88 4810468 6403 SELP 2.65 0.0214 89 3870647 9270 ITGB1BP1 2.62 0.0160 90 6420630 51435 SCARA3 2.62 0.0214 91 1300470 256691 MAMDC2 2.62 0.0044 92 3780221 643911 LOC643911 2.61 0.0045 93 6400274 55107 TMEM16A 2.60 0.0070 94 7050315 148808 MFSD4 2.59 0.0187 95 3870246 4915 NTRK2 2.59 0.0043 96 4290037 4856 NOV 2.59 0.0068 97 620349 4915 NTRK2 2.59 0.0013 98 6200333 6581 SLC22A3 2.58 0.0035 99 1430377 79785 RERGL 2.58 0.0015 100 4860743 163933 FAM43B 2.58 0.0010 101 6650280 114905 C1QTNF7 2.57 0.0021 102 7150762 5740 PTGIS 2.57 0.0317 103 5080259 3790 KCNS3 2.56 0.0015 104 5890091 78986 DUSP26 2.55 0.0079 105 110706 10278 EFS 2.55 0.0003 106 2850451 2322 FLT3 2.55 0.0241 107 4260554 6493 SIM2 2.54 0.0142 108 3310022 10265 IRX5 2.54 0.0049 109 2900286 100134444 LOC100134444 2.53 0.0064 110 1430682 NA 2.51 0.0002 111 4040246 2500 FTHL7 2.51 0.0127 112 6450129 9452 ITM2A 2.50 0.0011 113 5260291 5443 POMC 2.49 0.0149 114