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Am J Transplant. 2019 Jun 13. doi: 10.1111/ajt.15493. [Epub ahead of print]

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

Author information

1
Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
2
Renal Transplant Unit, Department of Internal Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
3
Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
4
Department of Nephrology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
5
Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
6
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
7
Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
8
Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
9
Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.
10
Department of Nephrology, Maastricht University Medical Center, Maastricht, The Netherlands.
11
Department of Nephrology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
12
Department of Immunogenetics, Sanquin Diagnostic Services, Amsterdam, The Netherlands.
13
Dutch Organ Transplant Registry (NOTR), Dutch Transplant Foundation (NTS), Leiden, The Netherlands.
14
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
15
Department of Nephrology, Erasmus Medical Center, Rotterdam, Department of Nephrology, Rotterdam, The Netherlands.
16
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.

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

PMID:
31194283
DOI:
10.1111/ajt.15493

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