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; 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; Marielle A. C. J. Gelens; Maarten H. L. Christiaans; Frans J. van Ittersum; Shaikh A. Nurmohamed; Neubury M. Lardy; Wendy Swelsen; Karlijn A. M. 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

doi:10.1111/ajt.15493

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, Marielle A. C. J. Gelens, Maarten H. L. Christiaans, Frans J. van Ittersum, Shaikh A. Nurmohamed, Neubury M. Lardy, Wendy Swelsen, Karlijn A. M. 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-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 language	English
Pages (from-to)	3335-3344
Number of pages	10
Journal	American Journal of Transplantation
Volume	19
Issue number	12
DOIs	https://doi.org/10.1111/ajt.15493
Publication status	Published - Dec 2019

Keywords

ARHGDIB
kidney transplantation
non-HLA antibodies
II TYPE-1 RECEPTOR
NON-HLA ANTIBODIES
PRETRANSPLANT SENSITIZATION
PHOSPHOLIPASE-A2 RECEPTOR
RISK-FACTOR
TRANSPLANTATION
REJECTION
ANTIGENS
IDENTIFICATION
TARGET

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Kamburova, E. G., Gruijters, M. L., Kardol-Hoefnagel, T., Wisse, B. W., Joosten, I., Allebes, W. A., van der Meer, A., Hilbrands, L. B., Baas, M. C., Spierings, E., Hack, C. E., van Reekum, F. E., van Zuilen, A. D., Verhaar, M. C., Bots, M. L., Drop, A. C. A. D., Plaisier, L., Melchers, R. C. A., Seelen, M. A. J., ... Otten, H. G. (2019). Antibodies against ARHGDIB are associated with long-term kidney graft loss. American Journal of Transplantation, 19(12), 3335-3344. https://doi.org/10.1111/ajt.15493

@article{cdc46f2329a94047865b83c086a0c0bc,

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.",

keywords = "ARHGDIB, kidney transplantation, non-HLA antibodies, II TYPE-1 RECEPTOR, NON-HLA ANTIBODIES, PRETRANSPLANT SENSITIZATION, PHOSPHOLIPASE-A2 RECEPTOR, RISK-FACTOR, TRANSPLANTATION, REJECTION, ANTIGENS, IDENTIFICATION, TARGET",

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, {Marielle 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.} 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.}",

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: {\textcopyright} 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.",

year = "2019",

month = dec,

doi = "10.1111/ajt.15493",

language = "English",

volume = "19",

pages = "3335--3344",

journal = "American Journal of Transplantation",

issn = "1600-6135",

publisher = "Wiley",

number = "12",

}

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, KAM, 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, vol. 19, no. 12, pp. 3335-3344. https://doi.org/10.1111/ajt.15493

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, Marielle 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.

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.

N1 - 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.

PY - 2019/12

Y1 - 2019/12

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.

KW - ARHGDIB

KW - kidney transplantation

KW - non-HLA antibodies

KW - II TYPE-1 RECEPTOR

KW - NON-HLA ANTIBODIES

KW - PRETRANSPLANT SENSITIZATION

KW - PHOSPHOLIPASE-A2 RECEPTOR

KW - RISK-FACTOR

KW - TRANSPLANTATION

KW - REJECTION

KW - ANTIGENS

KW - IDENTIFICATION

KW - TARGET

U2 - 10.1111/ajt.15493

DO - 10.1111/ajt.15493

M3 - Article

C2 - 31194283

SN - 1600-6135

VL - 19

SP - 3335

EP - 3344

JO - American Journal of Transplantation

JF - American Journal of Transplantation

IS - 12

ER -