Antibodies against ARHGDIB are associated with long-term kidney graft loss

Elena G. Kamburova, Maartje L. Gruijters, Tineke Kardol-Hoefnagel, Bram W. Wisse, Irma Joosten, Wil A. Allebes, Arnold van der Meer, Luuk B. Hilbrands, Marije C. Baas, Eric Spierings, Cornelis E. Hack, Franka E. van Reekum, Arjan D. van Zuilen, Marianne C. Verhaar, Michiel L. Bots, Adriaan C. A. D. Drop, Loes Plaisier, Rowena C. A. Melchers, Marc A. J. Seelen, Jan Stephan SandersBouke G. Hepkema, Annechien J. A. Lambeck, Laura B. Bungener, Caroline Roozendaal, Marcel G. J. Tilanus, Christina E. Voorter, Lotte Wieten, Elly M. van Duijnhoven, Mariëlle A. C. J. Gelens, Maarten H. L. Christiaans, Frans J. van Ittersum, Shaikh A. Nurmohamed, Neubury M. Lardy, Wendy Swelsen, Karlijn A. M. I. van der Pant, Neelke C. van der Weerd, Ineke J. M. ten Berge, Andries Hoitsma, Paul J. M. van der Boog, Johan W. de Fijter, Michiel G. H. Betjes, Sebastiaan Heidt, Dave L. Roelen, Frans H. Claas, Frederike J. Bemelman, Henny G. Otten

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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.
Original languageEnglish
Pages (from-to)3335-3344
Number of pages10
JournalAmerican Journal of Transplantation
Issue number12
Publication statusPublished - 1 Dec 2019

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