Antibodies against ARHGDIB are associated with long-term kidney graft loss
Kamburova, Elena G; Gruijters, Maartje L; Kardol-Hoefnagel, Tineke; Wisse, Bram W; Joosten, Irma; Allebes, Wil A; van der Meer, Arnold; Hilbrands, Luuk B; Baas, Marije C; Spierings, Eric; Hack, Cornelis E; van Reekum, Franka E; van Zuilen, Arjan D; Verhaar, Marianne C; Bots, Michiel L; Drop, Adriaan C A D; Plaisier, Loes; Melchers, Rowena C A; Seelen, Marc A J; Sanders, Jan Stephan; Hepkema, Bouke G; Lambeck, Annechien J A; Bungener, Laura B; Roozendaal, Caroline; Tilanus, Marcel G J; Voorter, Christina E; Wieten, Lotte; van Duijnhoven, Elly M; Gelens, Mariëlle A C J; Christiaans, Maarten H L; van Ittersum, Frans J; Nurmohamed, Shaikh A; Lardy, Neubury M; Swelsen, Wendy; van der Pant, Karlijn A M I; van der Weerd, Neelke C; Ten Berge, Ineke J M; Hoitsma, Andries; van der Boog, Paul J M; de Fijter, Johan W; Betjes, Michiel G H; Heidt, Sebastiaan; Roelen, Dave L; Claas, Frans H; Bemelman, Frederike J; Otten, Henny G
(2019) American Journal of Transplantation, volume 19, issue 12, pp. 3335 - 3344
(Article)
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
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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.
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Keywords: ARHGDIB, kidney transplantation, non-HLA antibodies, Transplantation, Pharmacology (medical), Immunology and Allergy, Journal Article
ISSN: 1600-6135
Publisher: Blackwell Publishing Asia Pty Ltd
Note: Funding Information: The authors thank Dr. Tri Nguyen (Department of Pathology, University Medical Center Utrecht, The Netherlands) for his assistance in performing and interpreting the anti-ARGHDIB staining on kidney tissue. This study was supported by research funding from the Dutch Kidney Foundation Project code CP12.23 Risk assessment of kidney graft failure by HLA antibody profiling. Publisher Copyright: © 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.
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