HLA-B8, DR3: a new risk factor for graft failure after renal transplantation in patients with underlying immunoglobulin A nephropathy

Background: The HLA-B8, DR3 haplotype has been associated with high immune reactivity. In this study, we have tested whether this haplotype has differential effect on graft survival in patients with IgAN compared with control patients. Methods: From the Eurotransplant Registry we analyzed graft survival of 1207 recipients with IgAN and 7935 control patients with non-glomerular diseases. Death-censored graft loss according to the HLA-B8, DR3 haplotype was calculated with Kaplan-Meier analysis and Cox-regression model was used to correct for various risk factors. Results: The frequency of the HLA-B8, DR3 haplotype was significantly lower in IgAN patients compared with controls (10.3% vs. 15.4%, p < 0.001). Ten-year graft survival was identical in the control group with and without the HLA-B8, DR3 haplotype (71.1% and 70.2%, respectively), but significantly worse in IgAN patients carrying the HLA-B8, DR3 haplotype compared with patients without it (52.5% vs. 69.1%, respectively, p = 0.009). The risk of graft loss was increased by 66% (HR 1.6, 95% CI 1.14, 2.29) in IgAN with the HLA-B8, DR3 haplotype and independent of well-known risk factors. Conclusions: We have identified a new risk factor for graft loss unique to patients with IgAN. This finding emphasizes the exclusive immune characteristics of IgAN patients after transplantation.