Transplant Glomerulopathy: Risk and Prognosis Related to Anti-Human Leukocyte Antigen Class II Antibody Levels

Abstract

Background. Transplant glomerulopathy (TG) is a histopathologic entity of kidney allografts related to anti-human leukocyte antigen (HLA) antibodies. The goal of this study was to determine the relationships among antibody characteristics (level and specificity), risk for TG, and graft survival. Methods. The presence and characteristics of anti-HLA antibody were assessed by single antigen beads assays in stored pretransplant sera from 598 kidney recipients with negative T-cell crossmatch. Transplant glomerulopathy was diagnosed by surveillance and clinical biopsies. Results. Thirty-nine percent of patients presented with anti-HLA antibodies pretransplant. Transplant glomerulopathy was diagnosed in 73 patients (12%) during 54±19 months of follow-up. The risk of TG increased with higher anti-HLA-II antibody levels (HR=1.890, 95% CI 1.42–2.52; PP=0.001), and in patients with history of antibody-mediated rejection (4.985 [2.77–8.97]; PP− and 80% of TG/C4d⁺ grafts failed (PP=0.007). Conclusions. In T-cell negative crossmatch patients, higher anti-HLA-II antibody levels are related to the increase in the risk of developing TG. Higher antibody levels are also related to the presence of C4d in peritubular capillaries in TG biopsies. Furthermore, the presence of C4d in TG is related to the reduced graft survival.