Class II HLA Eplet Load Is a Risk Factor for Transplant Glomerulopathy.

Abstract

Study purpose: The objective of this study was to assess the risk of developing transplant glomerulopathy as a function of donor and recipient class II HLA incompatibility at the eplet level. Methods: We conducted a nested case-control study from a cohort of kidney transplant recipients (KTR) transplanted at the University Health Network (UHN) January 1, 2000 to December 31, 2012. Cases (n=52) were defined as adult KTR diagnosed with transplant glomerulopathy based on kidney allograft biopsies showing glomerular basement membrane duplication without immune complex deposition. Controls (n=104) were randomly selected from the remaining cohort at the time of case diagnosis. HLAMatchmaker was used to ascertain the number of class II (DR and DQ) eplet mismatches, or the class II “eplet load,” from donors and recipients' 4-digit HLA typing. DRB1, DR3/4/5, DQA, and DQB typing was updated using molecular methods when absent. Class II eplet load was modeled both as a categorical (DR and DQ eplet load: <27, 27 to 43, >43) and continuous variable. We fit conditional logistic regression models adjusting for recipient, donor, and transplant characteristics to assess the association between transplant glomerulopathy and eplet load. Results: A significant increase in the odds of transplant glomerulopathy was observed across ascending categories of eplet load. The fully adjusted model showed odds ratios of transplant glomerulopathy of 2.84 (95% confidence interval: 1.03, 7.84) and 4.62 (95% CI: 1.51, 14.14) in the presence of 27 to 43 and >43 class II eplet mismatches vs. <27 eplet mismatches, respectively. When the eplet load was modelled as a continuous variable, the odds ratios for transplant glomerulopathy were 1.25 (95% CI: 1.04, 1.50), 1.63 (95% CI: 1.14, 2.33), and 1.27 (95% CI: 0.95, 1.69) for every 10 additional class II (DR and DQ), DR, and DQ eplet mismatches, respectively. Conclusions: Class II eplet load is an independent risk factor for transplant glomerulopathy. Minimization of class II HLA mismatches between donors and recipients at the eplet level and tailoring of immunosuppression regimens to eplet load may decrease the incidence of transplant glomerulopathy in kidney transplant recipients.