Major histocompatibility complex class I-related chain A allele mismatching, antibodies, and rejection in renal transplantation

Steven T. Cox, Henry A F Stephens, Raymond Fernando, Aliyye Karasu, Mark Harber, Alexander J. Howie, Stephen Powis, Yizhou Zou, Peter Stastny, J. Alejandro Madrigal, Ann Margaret Little

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Even when kidney allografts are well matched for human leukocyte antigen (HLA) and anti-HLA antibodies are not detected, graft rejection can still occur. There is evidence that some patients who lose their graft have antibodies specific for major histocompatibility complex (MHC) class I-related chain A (MICA) antigens. We investigated whether mismatching MICA alleles associates with MICA antibody production and graft rejection or dysfunction. MICA and HLA antibody screening in 442 recipients was performed, and specificities were confirmed in a subgroup of 227 recipients using single-antigen multiplex technology. For assignment of MICA antibody specificity, we used three independent assays. In addition, MICA alleles of 227 recipients and donors were determined by DNA sequencing. In all, 17 patients (7.5%) had MICA antibodies, and 13 patients (6%) developed MICA donor-specific antibodies (DSA). Multivariate analysis revealed MICA mismatching, as an independent significant factor associated with the presence of MICA antibodies (p = 0.009), and 14 mismatched MICA residues significantly correlated with MICA antibody production. MICA and HLA antibodies significantly associated with acute rejection (AR) and MICA DSA and HLA DSA correlated with decreased graft function by univariate and multivariate analysis. We conclude that mismatching for MICA epitopes in renal transplantation is a mechanism leading to production of MICA antibodies that associate with AR and graft dysfunction.

Original languageEnglish (US)
Pages (from-to)827-834
Number of pages8
JournalHuman Immunology
Volume72
Issue number10
DOIs
StatePublished - Oct 2011

Keywords

  • Antibodies
  • MICA
  • Mismatching
  • Rejection
  • Renal
  • Transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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