Polymorphisms in CTLA-4 predict de novo donor specific antibody formation after kidney transplantation

Hum Immunol. 2022 Jun;83(6):494-498. doi: 10.1016/j.humimm.2022.03.008. Epub 2022 Mar 29.

Abstract

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 present study, we investigated the impact of CTLA-4 SNPs on dnDSA formation after kidney transplantation (KT) by analyzing three CTLA-4 SNPs (rs231775, rs3087243, and rs5742909) in 88 recipients. 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. In conclusion, our findings indicate that CTLA-4 SNPs are predisposing factors for dnDSA formation after KT.

Keywords: Antibody-mediated rejection; Single-nucleotide polymorphism; Tailored immunosuppression.

MeSH terms

  • Antibodies
  • Antibody Formation
  • CTLA-4 Antigen* / genetics
  • Graft Rejection / genetics
  • Graft Survival / genetics
  • Humans
  • Isoantibodies*
  • Kidney Transplantation*
  • Retrospective Studies
  • Tissue Donors

Substances

  • Antibodies
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Isoantibodies