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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Abstract

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=0.0003). These antibodies occur independently from 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. This article is protected by copyright. All rights reserved.

Original languageEnglish
Number of pages10
JournalAmerican Journal of Transplantation
DOIs
Publication statusPublished - 3-Jul-2019

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