The Effects of Anti-BAFF Monoclonal Antibody in the HLA-A2 Sensitized Mouse Model
1Division of Nephrology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon-si, Korea, Republic of, 2Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of, 3Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of, 4Department of Molecular & Cell Biology, Graduate School, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of, 5Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of, 6Division of Nephrology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea, Republic of, 7Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of
Meeting: 2019 American Transplant Congress
Abstract number: 166
Keywords: Alloantibodies, Mice, Monoclonal antibodies, Sensitization
Session Information
Session Name: Concurrent Session: B-cell / Antibody /Autoimmunity
Session Type: Concurrent Session
Date: Sunday, June 2, 2019
Session Time: 4:30pm-6:00pm
Presentation Time: 4:30pm-4:42pm
Location: Room 310
*Purpose: B-cell activating factor (BAFF) is a cytokine that plays a role in the survival, proliferation and differentiation of B-cells. The aim of this study is to develop an allosensitized mouse model using HLA.A2 transgenic mice, and to observe the effects of anti-BAFF monoclonal antibody (mAb) in this model.
*Methods: Wild-type C57BL/6 mice were sensitized with skin allografts from C57BL/6-Tg (HLA-A2.1)1Enge/J mice and were treated with intraperitoneal injections of anti-BAFF mAb (named Sandy-2) or control IgG1 antibody. Donor specific antibody (DSA) responses were observed by measuring anti-HLA.A2 antibodies in serum of the mice using the luminex assay. B-cell fractions in mice bone marrow and spleen were determined using flow cytometric analysis, and mRNA profiling was done using microarray analysis.
*Results: HLA.A2-specific IgG was reduced in mice injected with anti-BAFF mAb compared to the control group (Δ-15.8±6.7 vs.Δ42.2±64.7, p = 0.1). BAFF blockade resulted in increased pre-pro and immature B-cell proportions in the bone marrow and decreased mature B-cells (p<0.05 vs. control). In the spleen as well, an increase in the proportion of transitional B-cells was observed with a significant decrease in marginal and follicular B-cells (p<0.05 vs. control). There was no significant difference in proportions of long lived plasma cells in the bone marrow and memory B-cells in the spleen. Microarray analysis results showed that, 19 genes were significantly up (>2 fold, p<0.05) or down regulated (<2 fold, p<0.05) in the BAFF blockade group. On further analysis using the CIBERSORT method, gene set enrichment results showed that the IL12 pathway, NO-IL12 pathway and CSK pathways were most significantly enriched (Nominal p-value <0.05, FDR <25%) in the BAFF blockade group.
*Conclusions: Anti-BAFF monoclonal antibody inhibited anti-HLA.A2 responses resulting in reduction of HLA.A2-specific IgG and significantly inhibited differentiation and maturation of B cells in both the bone marrow and spleen. Our data suggests that BAFF suppression may serve as a useful target in desensitization therapy.
To cite this abstract in AMA style:
Min J, Lee H, Kim B, Park K, Doh K, Kim T, Yoon H, Yang C, Oh E, Chung B. The Effects of Anti-BAFF Monoclonal Antibody in the HLA-A2 Sensitized Mouse Model [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/the-effects-of-anti-baff-monoclonal-antibody-in-the-hla-a2-sensitized-mouse-model/. Accessed May 9, 2025.« Back to 2019 American Transplant Congress