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


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 = .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.

SUBMITTER: Kamburova EG 

PROVIDER: S-EPMC6899679 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Kamburova Elena G EG   Gruijters Maartje L ML   Kardol-Hoefnagel Tineke T   Wisse Bram W BW   Joosten Irma I   Allebes Wil A WA   van der Meer Arnold A   Hilbrands Luuk B LB   Baas Marije C MC   Spierings Eric E   Hack Cornelis E CE   van Reekum Franka E FE   van Zuilen Arjan D AD   Verhaar Marianne C MC   Bots Michiel L ML   Drop Adriaan C A D ACAD   Plaisier Loes L   Melchers Rowena C A RCA   Seelen Marc A J MAJ   Sanders Jan Stephan JS   Hepkema Bouke G BG   Lambeck Annechien J A AJA   Bungener Laura B LB   Roozendaal Caroline C   Tilanus Marcel G J MGJ   Voorter Christina E CE   Wieten Lotte L   van Duijnhoven Elly M EM   Gelens Mariëlle A C J MACJ   Christiaans Maarten H L MHL   van Ittersum Frans J FJ   Nurmohamed Shaikh A SA   Lardy Neubury M NM   Swelsen Wendy W   van der Pant Karlijn A M I KAMI   van der Weerd Neelke C NC   Ten Berge Ineke J M IJM   Hoitsma Andries A   van der Boog Paul J M PJM   de Fijter Johan W JW   Betjes Michiel G H MGH   Heidt Sebastiaan S   Roelen Dave L DL   Claas Frans H FH   Bemelman Frederike J FJ   Otten Henny G HG  

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20190703 12


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 transplante  ...[more]

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