Polymorphisms in Ctla-4 Predict De Novo Donor Specific Antibody Formation After Kidney Transplantation
Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health S, Hiroshima University, Hiroshima City, Japan
Meeting: 2022 American Transplant Congress
Abstract number: 1404
Keywords: Antibodies, Gene polymorphism, Kidney transplantation
Topic: Clinical Science » Kidney » 45 - Kidney Chronic Antibody Mediated Rejection
Session Information
Session Name: Kidney Chronic Antibody Mediated Rejection
Session Type: Poster Abstract
Date: Monday, June 6, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: The post-transplant development of donor-specific antibodies (DSAs) initiates the antibody-mediated rejection, which is associated with an increased rate of graft loss. Therefore, risk prediction of de novo DSA (dnDSA) is important for understanding long-term prognostic implications for kidney transplantation outcomes. Cytotoxic T lymphocyte antigen-4 (CTLA-4), a cell surface molecule, suppresses T cell responses. Single-nucleotide polymorphisms (SNPs) in CTLA-4 are known to be associated with acute rejection; however, their association with dnDSA formation is not established. In the current study, we investigated the association of three CTLA-4 SNPs, namely rs231775, rs3087243, and rs5742909 with dnDSA formation in KT recipients.
*Methods: A total of 108 patients underwent living-donor kidney transplantation at the Hiroshima University Hospital between April 2011 and March 2019. Of these, 20 patients were excluded from the study because of re-transplantation (n = 4), presence of DSAs at the time of KT (n = 13) or having a follow-up period of less than 1 year (n = 2). The remaining 88 patients (54 ABO-blood-type compatible recipients and 34 ABO-blood-type incompatible recipients) were enrolled in this study. The three CTLA-4 SNPs, rs231775, rs3087243, and rs5742909 were detected using direct DNA sequencing methods.
*Results: Among 88 KT recipients, 11 (12.5%) developed dnDSA during the observation period. Statistically significant differences in any other baseline characteristics between patients with and without dnDSA formation were not observed. On the other hand, the GG genotype of rs231775 and the GG genotype of rs3087243 tended to have a higher incidence of dnDSA formation. The combination of rs231775 and rs3087243 further stratified the incidence of dnDSA formation. Patients with the GG genotype of CTLA-4 SNPs rs231775 and rs3087243 had higher rates of dnDSA formation than patients with the AA genotype or heterozygous genotypes (22.3% vs 7.0%, p=0.04).
*Conclusions: The CTLA-4 SNPs in KT recipients were found to be significantly associated with dnDSA formation and a rigorously designed, large-scale prospective study is essential to further validate these results.
To cite this abstract in AMA style:
Ono K, Ide K, Yamane H, Akimoto S, Tanimine N, Tahara H, Ohira M, Tanaka Y, Ohdan H. Polymorphisms in Ctla-4 Predict De Novo Donor Specific Antibody Formation After Kidney Transplantation [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/polymorphisms-in-ctla-4-predict-de-novo-donor-specific-antibody-formation-after-kidney-transplantation/. Accessed May 18, 2025.« Back to 2022 American Transplant Congress