Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure

Elena G. Kamburova; 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; 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. I. van der Pant; Neelke C. van der Weerd; Ineke J. M. ten Berge; Frederike J. Bemelman; Andries J. Hoitsma; Paul J. M. van der Boog; Johan W. de Fijter; Michiel G. H. Betjes; Sebastiaan Heidt; Dave L. Roelen; Frans H. Claas; Henny G. Otten

doi:10.1681/ASN.2018020205

Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure

Elena G. Kamburova^*, 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, Marc A. J. Seelen, Jan Stephan Sanders, Bouke G. Hepkema, Annechien J. A. Lambeck, Laura B. BungenerCaroline 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. I. van der Pant, Neelke C. van der Weerd, Ineke J. M. ten Berge, Frederike J. Bemelman, Andries J. Hoitsma, Paul J. M. van der Boog, Johan W. de Fijter, Michiel G. H. Betjes, Sebastiaan Heidt, Dave L. Roelen, Frans H. Claas, Henny G. Otten

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

16 Citations (Web of Science)

Abstract

Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. Amodification of the IgG single-antigenbead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients. Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay. Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non-C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non-C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non-C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%. Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.

Original language	English
Pages (from-to)	2279-2285
Number of pages	7
Journal	Journal of the American Society of Nephrology
Volume	29
Issue number	9
DOIs	https://doi.org/10.1681/ASN.2018020205
Publication status	Published - 1 Sep 2018

Keywords

chronic allograft failure
kidney transplantation
anti-HLA antibodies
complement-fixing antibodies
C1Q ASSAY
TRANSPLANTATION
RECIPIENTS
SURVIVAL

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10.1681/ASN.2018020205

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Kamburova, E. G., 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., Seelen, M. A. J., Sanders, J. S., Hepkema, B. G., Lambeck, A. J. A., ... Otten, H. G. (2018). Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure. Journal of the American Society of Nephrology, 29(9), 2279-2285. https://doi.org/10.1681/ASN.2018020205

@article{bcb5636543f64b2ea1e4280ca39f46a6,

title = "Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure",

abstract = "Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. Amodification of the IgG single-antigenbead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients. Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay. Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non-C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non-C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non-C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%. Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.",

keywords = "chronic allograft failure, kidney transplantation, anti-HLA antibodies, complement-fixing antibodies, C1Q ASSAY, TRANSPLANTATION, RECIPIENTS, SURVIVAL",

author = "Kamburova, {Elena G.} 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 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. I.} and {van der Weerd}, {Neelke C.} and {ten Berge}, {Ineke J. M.} and Bemelman, {Frederike J.} and Hoitsma, {Andries J.} 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 Otten, {Henny G.}",

year = "2018",

month = sep,

day = "1",

doi = "10.1681/ASN.2018020205",

language = "English",

volume = "29",

pages = "2279--2285",

journal = "Journal of the American Society of Nephrology",

issn = "1046-6673",

publisher = "American Society of Nephrology",

number = "9",

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Kamburova, EG, 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, 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, Bemelman, FJ, Hoitsma, AJ, van der Boog, PJM, de Fijter, JW, Betjes, MGH, Heidt, S, Roelen, DL, Claas, FH & Otten, HG 2018, 'Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure', Journal of the American Society of Nephrology, vol. 29, no. 9, pp. 2279-2285. https://doi.org/10.1681/ASN.2018020205

TY - JOUR

T1 - Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure

AU - Kamburova, Elena G.

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 - 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. I.

AU - van der Weerd, Neelke C.

AU - ten Berge, Ineke J. M.

AU - Bemelman, Frederike J.

AU - Hoitsma, Andries J.

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 - Otten, Henny G.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. Amodification of the IgG single-antigenbead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients. Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay. Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non-C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non-C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non-C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%. Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.

AB - Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. Amodification of the IgG single-antigenbead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients. Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay. Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non-C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non-C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non-C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%. Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.

KW - chronic allograft failure

KW - kidney transplantation

KW - anti-HLA antibodies

KW - complement-fixing antibodies

KW - C1Q ASSAY

KW - TRANSPLANTATION

KW - RECIPIENTS

KW - SURVIVAL

U2 - 10.1681/ASN.2018020205

DO - 10.1681/ASN.2018020205

M3 - Article

C2 - 30049681

VL - 29

SP - 2279

EP - 2285

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 9

ER -