TY - JOUR
T1 - Antibodies against ARHGDIB are associated with long-term kidney graft loss
AU - Kamburova, Elena G.
AU - Gruijters, Maartje L.
AU - Kardol-Hoefnagel, Tineke
AU - Wisse, Bram W.
AU - Joosten, Irma
AU - Allebes, Wil A.
AU - van der Meer, Arnold
AU - Hilbrands, Luuk B.
AU - Baas, Marije C.
AU - Spierings, Eric
AU - Hack, Cornelis E.
AU - van Reekum, Franka E.
AU - van Zuilen, Arjan D.
AU - Verhaar, Marianne C.
AU - Bots, Michiel L.
AU - Drop, Adriaan C. A. D.
AU - Plaisier, Loes
AU - Melchers, Rowena C. A.
AU - Seelen, Marc A. J.
AU - Sanders, Jan Stephan
AU - Hepkema, Bouke G.
AU - Lambeck, Annechien J. A.
AU - Bungener, Laura B.
AU - Roozendaal, Caroline
AU - Tilanus, Marcel G. J.
AU - Voorter, Christina E.
AU - Wieten, Lotte
AU - van Duijnhoven, Elly M.
AU - Gelens, Mariëlle A. C. J.
AU - Christiaans, Maarten H. L.
AU - van Ittersum, Frans J.
AU - Nurmohamed, Shaikh A.
AU - Lardy, Neubury M.
AU - Swelsen, Wendy
AU - van der Pant, Karlijn A. M. I.
AU - van der Weerd, Neelke C.
AU - ten Berge, Ineke J. M.
AU - Hoitsma, Andries
AU - van der Boog, Paul J. M.
AU - de Fijter, Johan W.
AU - Betjes, Michiel G. H.
AU - Heidt, Sebastiaan
AU - Roelen, Dave L.
AU - Claas, Frans H.
AU - Bemelman, Frederike J.
AU - Otten, Henny G.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85067525646&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31194283
U2 - 10.1111/ajt.15493
DO - 10.1111/ajt.15493
M3 - Article
C2 - 31194283
VL - 19
SP - 3335
EP - 3344
JO - American Journal of Transplantation
JF - American Journal of Transplantation
SN - 1600-6135
IS - 12
ER -