Antibodies against ARHGDIB are associated with long-term kidney graft loss.
Elena G KamburovaMaartje L GruijtersTineke Kardol-HoefnagelBram W WisseIrma JoostenWil A AllebesArnold van der MeerLuuk B HilbrandsMarije C BaasEric SpieringsCornelis E HackFranka E van ReekumArjan D van ZuilenMarianne C VerhaarMichiel L BotsAdriaan C A D DropLoes PlaisierRowena C A MelchersMarc A J SeelenJan Stephan SandersBouke G HepkemaAnnechien J A LambeckLaura B BungenerCaroline RoozendaalMarcel G J TilanusChristina E VoorterLotte WietenElly M van DuijnhovenMariëlle A C J GelensMaarten H L ChristiaansFrans J van IttersumShaikh A NurmohamedNeubury M LardyWendy SwelsenKarlijn A M I van der PantNeelke C van der WeerdIneke J M Ten BergeAndries HoitsmaPaul J M van der BoogJohan W de FijterMichiel G H BetjesSebastiaan HeidtDave L RoelenFrans H ClaasFrederike J BemelmanElena G KamburovaPublished in: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (2019)
The clinical significance of non-HLA antibodies on renal allograft survival is a matter of debate, due to differences in reported results and lack of large-scale studies incorporating analysis of multiple non-HLA antibodies simultaneously. We developed a multiplex non-HLA antibody assay against 14 proteins highly expressed in the kidney. In this study, the presence of pretransplant non-HLA antibodies was correlated to renal allograft survival in a nationwide cohort of 4770 recipients transplanted between 1995 and 2006. Autoantibodies against Rho GDP-dissociation inhibitor 2 (ARHGDIB) were significantly associated with graft loss in recipients transplanted with a deceased-donor kidney (N = 3276) but not in recipients of a living-donor kidney (N = 1496). At 10 years after deceased-donor transplantation, recipients with anti-ARHGDIB antibodies (94/3276 = 2.9%) had a 13% lower death-censored covariate-adjusted graft survival compared to the anti-ARHGDIB-negative (3182/3276 = 97.1%) population (hazard ratio 1.82; 95% confidence interval, 1.32-2.53; P = .0003). These antibodies occur independently from donor-specific anti-HLA antibodies (DSA) or other non-HLA antibodies investigated. No significant relations with graft loss were found for the other 13 non-HLA antibodies. We suggest that pretransplant risk assessment can be improved by measuring anti-ARHGDIB antibodies in all patients awaiting deceased-donor transplantation.