Prevalence and impact of HLA and MICA allele mismatching on donor-specific antibodies induction in kidney transplant rejection

Nephrology (Carlton). 2021 Oct;26(10):833-841. doi: 10.1111/nep.13921. Epub 2021 Jul 6.

Abstract

Aim: Donor-recipient antigen mismatching for anti-human leucocyte antigen (HLA) and MICA is one of the risk factors for antibody induction leading to graft rejection. Our aim was to analyze the incidence and specificity of the different DSAs developing and to investigate the impact of HLA and MICA allele mismatches on antibody production in kidney transplant patients experiencing antibody-mediated rejection (AMR).

Methods: We retrospectively reviewed 253 consecutive recipients of kidney transplant who were diagnosed as experiencing AMR.

Results: Our results showed that around 27% of our patients were positive for DSAs over a median follow-up period of 24 months. Antibody to HLA-DQ7 was the most prevalent DSA detected. The allele mismatch number was significantly lower for DQ loci than -A and -B loci (DQ vs. A, p < .001; DQ vs. B, p = .002). Considering each HLA antigen, the incidence rate of DQ-DSA [41.9 (32.92-51.46; 95%CI)] was much higher than the rate observed for DSA directed to -A, -DR and -B loci. Half of the recipients in the DQ-DSA-only group, and the DQ-DSA together with non-DQ group, had MFI > 5000. Only one case developed de novo MICA-DSA (MICA002).

Conclusion: Our study indicates that mismatching for HLA and MICA alleles leads to the development of HLA and MICA antibodies in some kidney transplant recipients. We have also demonstrated that DSA to the DQ locus is the most prevalent in kidney transplant patients with AMR. Thus, matching the DQ locus in kidney allocation algorithms may reduce post-transplant development of DSA.

Keywords: HLA-mismatching; MICA-mismatching; antibody-mediated rejection; donor-specific antibodies; kidney transplantation.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Female
  • Gene Frequency
  • Graft Rejection / blood
  • Graft Rejection / diagnosis
  • Graft Rejection / immunology*
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Testing
  • Histocompatibility*
  • Humans
  • Isoantibodies / blood*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Thailand
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Isoantibodies
  • MHC class I-related chain A