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 Sanders & 26 others Bouke 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

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
JournalAmerican Journal of Transplantation
DOIs
Publication statusPublished - 1 Jan 2019

Cite this

Kamburova, E. G., Gruijters, M. L., Kardol-Hoefnagel, T., Wisse, B. W., Joosten, I., Allebes, W. A., ... Otten, H. G. (2019). Antibodies against ARHGDIB are associated with long-term kidney graft loss. American Journal of Transplantation. https://doi.org/10.1111/ajt.15493
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. / Antibodies against ARHGDIB are associated with long-term kidney graft loss. In: American Journal of Transplantation. 2019.
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title = "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.",
author = "Kamburova, {Elena G.} and Gruijters, {Maartje L.} and Tineke Kardol-Hoefnagel and Wisse, {Bram W.} and Irma Joosten and Allebes, {Wil A.} and {van der Meer}, Arnold and Hilbrands, {Luuk B.} and Baas, {Marije C.} and Eric Spierings and Hack, {Cornelis E.} and {van Reekum}, {Franka E.} and {van Zuilen}, {Arjan D.} and Verhaar, {Marianne C.} and Bots, {Michiel L.} and Drop, {Adriaan C. A. D.} and Loes Plaisier and Melchers, {Rowena C. A.} and Seelen, {Marc A. J.} and Sanders, {Jan Stephan} and Hepkema, {Bouke G.} and Lambeck, {Annechien J. A.} and Bungener, {Laura B.} and Caroline Roozendaal and Tilanus, {Marcel G. J.} and Voorter, {Christina E.} and Lotte Wieten and {van Duijnhoven}, {Elly M.} and Gelens, {Mari{\"e}lle A. C. J.} and Christiaans, {Maarten H. L.} and {van Ittersum}, {Frans J.} and Nurmohamed, {Shaikh A.} and Lardy, {Neubury M.} and Wendy Swelsen and {van der Pant}, {Karlijn A. M. I.} and {van der Weerd}, {Neelke C.} and {ten Berge}, {Ineke J. M.} and Andries Hoitsma and {van der Boog}, {Paul J. M.} and {de Fijter}, {Johan W.} and Betjes, {Michiel G. H.} and Sebastiaan Heidt and Roelen, {Dave L.} and Claas, {Frans H.} and Bemelman, {Frederike J.} and Otten, {Henny G.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/ajt.15493",
language = "English",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",

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Kamburova, EG, Gruijters, ML, Kardol-Hoefnagel, T, Wisse, BW, Joosten, I, Allebes, WA, van der Meer, A, Hilbrands, LB, Baas, MC, Spierings, E, Hack, CE, van Reekum, FE, van Zuilen, AD, Verhaar, MC, Bots, ML, Drop, ACAD, Plaisier, L, Melchers, RCA, Seelen, MAJ, Sanders, JS, Hepkema, BG, Lambeck, AJA, Bungener, LB, Roozendaal, C, Tilanus, MGJ, Voorter, CE, Wieten, L, van Duijnhoven, EM, Gelens, MACJ, Christiaans, MHL, van Ittersum, FJ, Nurmohamed, SA, Lardy, NM, Swelsen, W, van der Pant, KAMI, van der Weerd, NC, ten Berge, IJM, Hoitsma, A, van der Boog, PJM, de Fijter, JW, Betjes, MGH, Heidt, S, Roelen, DL, Claas, FH, Bemelman, FJ & Otten, HG 2019, 'Antibodies against ARHGDIB are associated with long-term kidney graft loss' American Journal of Transplantation. https://doi.org/10.1111/ajt.15493

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.

In: American Journal of Transplantation, 01.01.2019.

Research output: Contribution to journalArticleAcademicpeer-review

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 - 2019/1/1

Y1 - 2019/1/1

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

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

ER -

Kamburova EG, Gruijters ML, Kardol-Hoefnagel T, Wisse BW, Joosten I, Allebes WA et al. Antibodies against ARHGDIB are associated with long-term kidney graft loss. American Journal of Transplantation. 2019 Jan 1. https://doi.org/10.1111/ajt.15493