Evidence for the alloimmune basis and prognostic significance of Borderline T cell-mediated rejection

Am J Transplant. 2020 Sep;20(9):2499-2508. doi: 10.1111/ajt.15860. Epub 2020 Apr 9.

Abstract

Prognostic biomarkers of T cell-mediated rejection (TCMR) have not been adequately studied in the modern era. We evaluated 803 renal transplant recipients and correlated HLA-DR/DQ molecular mismatch alloimmune risk categories (low, intermediate, high) with the severity, frequency, and persistence of TCMR. Allograft survival was reduced in recipients with Banff Borderline (hazard ratio [HR] 2.4, P = .003) and Banff ≥ IA TCMR (HR 4.3, P < .0001) including a subset who never developed de novo donor-specific antibodies (P = .002). HLA-DR/DQ molecular mismatch alloimmune risk categories were multivariate correlates of Banff Borderline and Banff ≥ IA TCMR and correlated with the severity and frequency of rejection episodes. Recipient age, HLA-DR/DQ molecular mismatch category, and cyclosporin vs tacrolimus immunosuppression were independent correlates of Banff Borderline and Banff ≥ IA TCMR. In the subset treated with tacrolimus (720/803) recipient age, HLA-DR/DQ molecular mismatch category, and tacrolimus coefficient of variation were independent correlates of TCMR. The correlation of HLA-DR/DQ molecular mismatch category with TCMR, including Borderline, provides evidence for their alloimmune basis. HLA-DR/DQ molecular mismatch may represent a precise prognostic biomarker that can be applied to tailor immunosuppression or design clinical trials based on individual patient risk.

Keywords: T cell-mediated rejection (TCMR); clinical research / practice; graft survival; histocompatibility; immunosuppression / immune modulation; kidney transplantation / nephrology; major histocompatibility complex (MHC); risk assessment / risk stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Graft Rejection* / diagnosis
  • Graft Rejection* / etiology
  • Graft Survival
  • Histocompatibility
  • Humans
  • Kidney Transplantation* / adverse effects
  • Prognosis
  • T-Lymphocytes

Grant support