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Selected Abstracts from the 12 Annual Journal of Clinical Immunology (2021) 41 (Suppl 1):S1–S135 https://doi.org/10.1007/s10875-021-01001-x ABSTRACTS Selected Abstracts from the 12th Annual Meeting of the Clinical Immunology Society: 2021 Virtual Annual Meeting: Immune Deficiency and Dysregulation North American Conference Published online: 6 April 2021 # Springer Science+Business Media, LLC, part of Springer Nature 2021 Virtual, April 14-17 The study samples were cleared cryo-poor plasma. A chromatographic process using a new cation-exchange (CEX) resin that binds with high Sponsorship: Publication of this supplement was funded by the capacity to IgG and removes procoagulant activities was added in a se- Clinical Immunology Society. All content was reviewed and approved quential step to the standard removal/inactivation process. Testing of the by the Program Committee, which held full responsibility for the samples was performed using the standard process alone and then with abstract selections. sequential addition of the new CEX process. Procoagulant activity was tested using several standard methods, including, thrombin generation All contributors have provided original material assay, chromogenic FXIa assay, non-activated partial thromboplastin as submitted for publication in the Journal time (NaPTT), and FXI/FXIa ELISA. We further spiked our samples with of Clinical Immunology. additional coagulation factor XIa, in amounts exceeding any variability that may be caused due to sample differences, and tested these samples 01 Oral Presentations for procoagulant activity using the same methods. The procoagulant activities were reduced to low levels as determined by the thrombin generation assay: < 1.56 mIU/mL, chromogenic FXIa assay: < 0.16 mIU/mL, NaPTT: >250 s, FXI/FXIa ELISA: < 0.31 ng/mL. Even (1) A new manufacturing process to remove thrombogenic factors after spiking with FXIa at a concentration 32.5 times higher than the (II, VII, IX, X, and XI) from intravenous immunoglobulin gamma concentration in normal specimens, the procoagulant activities were be- preparations low the detection limit ( < 0.31 ng/mL). We successfully removed the coagulation factors FII, FVII, FIX, and FX Alan Huber, PharmD MBA1, Dong Hwarn Park, PhD2, through cold ethanol precipitation, and removed FXIa using chromatog- Gil Bu Kang, PhD3, Dae Eun Kang, MSc4, raphy. Using this novel technology can potentially reduce future throm- Ki Yong Kim, PhD4, Jeung Woon Hong, PhD5, boembolic events with IVIG since FXIa is virtually eliminated. Min Gyu Lee, PhD6, Jeung Whan Han, PhD7 These results demonstrate the ability of our manufacturing process to 1Director of Medical Affairs US/GC Mogam Inc remove procoagulant activities to below the detection limit (except by 2Head, Research and Development/GC Corporation NaPTT), suggesting a reduced risk of thromboembolic events that may be 3Deputy Director, Research and Development/GC Corporation potentially caused by our IVIG preparation. 4Research and Development/GC Corporation 5Director of Bioassay/GC Corporation 6Faculty, School of Pharmacy/Sungkyunkwan University 7Faculty, School of Medicine/SungkyunKwan University Coagulation factors (II, VII, IX, X, and particularly XIa) remain- ing in high concentrations in intravenous immunoglobulin (IVIG) preparations can form thrombi, causing thromboembolic events, and in serious cases, death. Therefore, manufacturers of biological products must investigate the ability of their production processes to remove procoagulant activities. Previously, we were able to remove coagulation factors II, VII, IX, and X from our IVIG preparation through ethanol precipitation, but factor XIa, which plays an important role in thrombosis, remained in the intermedi- ate products. Therefore, our objective was to develop and test a process to remove factor XIa from IVIG. S2 J Clin Immunol (2021) 41 (Suppl 1):S1–S135 Keywords: immunoglobulin, chromatography, Factor Xia homozygous mutations in CARMIL2 has been linked to a broad range of manifestations, including allergies of the skin and respiratory tract; Disclosures: All authors indicated they had no financial relationships serious bacterial, fungal and viral infections such as disseminated warts to disclose. and molluscum; EBV-related smooth muscle tumors; chronic diarrhea and growth retardation. We present a single center experience on CARMIL2 patients. We studied seven patients (1 Male, 6 Females; current age: 16.7 years) from 4 independent families. Mean age at onset of symp- (2) CARMIL2 Deficiency And Various Clinical Phenotypes: toms was 48,8 months. P1 and P2 presented with chronic abdom- Warning Signs For Early Diagnosis inal pain and bloody diarrhea. P3 and P4, sisters, had eczema, recurrent respiratory and skin infectins including warts and 1 1 Burcu Kocamis Kolukisa, MD , Nurhan Kasap, MD , molluscum. P5 presented with early-onset IBD and wheezing. P6 2 2 2 Sevgi Bilgic Eltan, MD , Dilek Baser, MSc , Gamze Akgun, , and P7, cousins, had recurrent skin and airway infections, eczema 1 3 Asena Pınar Sefer, MD ,YaseminKendirDemirkol,MD, and warts. Eosinophilia was observed in 3/6 patients. Serum im- 4 5 Elif Karakoc Aydiner, MD , Ekrem Unal, MD , munoglobulins were normal in half, low IgG in two, high IgG, 4 4 Ahmet Ozen, MD ,SafaBaris,MD IgA, IgM in one patient. Protein antibody responses were poor in 1 Clinical Fellow/Marmara University Hospital, Department of Pediatric all patients. Flow cytometry revealed low NK-cells in 5 of 6 Immunology and Allergy subjects; elevated naïve CD4+ T cells in 3 of 6, and reduced 2 Marmara University Hospital, Department of Pediatric Immunology memory B cells in 2 of 6. Regulatory T-cells (Tregs) and induc- and Allergy tion of CTLA4 were reduced in all patients. Defective CD28 T- 3 Umraniye Research and Training Hospital, Department of Pediatric cell stimulation and cytokine production was confirmed in 2 pa- Genetic Diseases tients (P3 and P7). 4 Professor of Pediatrics/Marmara University Hospital, Department CARMIL2 deficiency may present with early onset-IBD, viral infections, of Pediatric Immunology and Allergy eczema and malignancies. Increased naive T cells, observed in majority 5 Erciyes University, Department of Pediatric Hematology of patients suggests defective differentiation. Knowledge of diverse man- and Oncology ifestations related to CARMIL2 deficiency should be envisaged for time- ly diagnosis. CARMIL2(RLTPR) gene regulates CD28 co-signalization and cytoskel- This work was supported by the Scientific and Technological Research etal dynamics of immune cells. Immune deficiency caused by Council of Turkey (318S202). Table 1 J Clin Immunol (2021) 41 (Suppl 1):S1–S135 S3 Keywords: CARMIL2, combined immunodeficiency, Treg Disclosures: All authors indicated they had no financial relationships to disclose. (3) Excess IL-18 and perforin deficiency distinctly and synergistically promote pathologic CD8 T-cell activation and experimental Hemophagocytic Lymphohistiocytosis Emily Landy, B.S.1, Scott Canna, MD2 1PhD Candidate/University of Pittsburgh 2Assistant Professor/University of Pittsburgh, UPMC Childrens Hospital Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS) are life-threatening hyperinflammatory cytokine storm syndromes. Familial HLH is associated with genetic Figure 1: Dysregulation of the immune systems response to antigen/ impairment of cytotoxic function (e.g. perforin deficiency), and infection can lead to hyperinflammation. Excess free IL-18 (as seen in Prf1-/- mice succumb to typically-mild LCMV infection via CD8 MAS) can hyperactivate CD8 T cells. Perforin deficiency (as seen in T-cell/IFNγ-mediated immunopathology. MAS is clinically similar fHLH) can also lead to hyperactivated CD8 T cells along with lack of to HLH, but occurs in certain rheumatic/autoinflammatory diseases antigen removal. Together these factors can combine to cause spontane- and has been associated with extraordinarily and chronically elevat- ous hyperinflammation in mice. ed serum IL-18. Improved understanding of their pathogenesis could significantly alter patient screening, diagnosis, and Keywords: HLH, MAS, IL-18, Perforin Deficiency, CD8 T cell, activation management. Using mice with excess IL-18 (Il18tg) to model a state of sus- Disclosures: Scott Canna received research grants from AB2Bio Ltd and ceptibility to MAS, we found some baseline abnormalities includ- IMMvention Therapeutix. Emily Landy had no financial relationships to ed decreased IL-18 receptor expression on NK cells and increased disclose. PD-1+ CD8 T-cells. Il18tg mice, but not Prf1-/- mice, developed more severe immunopathology in the TLR9-triggered model of MAS. Il18tg mice also developed MAS-like immunopathology (4) Long-term Safety Data from Pregnant Women Treated upon infection with LCMV (Armstrong), which was largely me- with Facilitated Subcutaneous Immunoglobulin (fSCIG) diated through CD8 T cells and IFNγ. As with LCMV-infected in a Pregnancy Registry Study Prf1-/- mice, CD8 T cells from LCMV-infected Il18tg mice showed increased activation and cytokine production, but did Michael Borte, Prof. Dr. med.1, Stefan Raffac, MUDr.2, not exhibit cytotoxic impairment or persistent antigen presenta- Martin Hrubisko, MD, PhD3, Karina Jahnz-Rozyk, MD, PhD4, tion. They retained KLRG1+ terminal effector differentiation and Milada Cvackova, MD5, Enrique Garcia, MD, MBA6, their transcriptional program was more comparable to WT than Andras Nagy, MD7, Barbara McCoy, PhD8,LemanYel,MD9 Prf1-/- mice in their absence of an exhaustion signature. 1Director,
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