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; 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

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, 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

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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=0.0003). These antibodies occur independently from 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. This article is protected by copyright. All rights reserved.

Originele taal-2	English
Aantal pagina's	10
Tijdschrift	American Journal of Transplantation
DOI's	https://doi.org/10.1111/ajt.15493
Status	Published - 3-jul.-2019

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Antibodies against ARHGDIB are associated with long‐term kidney graft lossFinal publisher's version, 1,08 MBLicentie: CC BY-NC

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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. https://doi.org/10.1111/ajt.15493

@article{6f2841ff0e56430090b1bf6e7ed660e0,

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=0.0003). These antibodies occur independently from 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. This article is protected by copyright. All rights reserved.",

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 = jul,

day = "3",

doi = "10.1111/ajt.15493",

language = "English",

journal = "American Journal of Transplantation",

issn = "1600-6135",

publisher = "Wiley",

}

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

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 - 2019/7/3

Y1 - 2019/7/3

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=0.0003). These antibodies occur independently from 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. This article is protected by copyright. All rights reserved.

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=0.0003). These antibodies occur independently from 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. This article is protected by copyright. All rights reserved.

U2 - 10.1111/ajt.15493

DO - 10.1111/ajt.15493

M3 - Article

C2 - 31194283

SN - 1600-6135

JO - American Journal of Transplantation

JF - American Journal of Transplantation

ER -

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

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