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Kidney Int. 2018 Oct;94(4):773-787. doi: 10.1016/j.kint.2018.03.015. Epub 2018 May 22.

Complement-binding anti-HLA antibodies are independent predictors of response to treatment in kidney recipients with antibody-mediated rejection.

Author information

1
Paris Translational Research Center for Organ Transplantation, Institut national de la santé et de la recherche médicale, Unité mixte de recherche-S970, Paris, France; Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
2
Paris Translational Research Center for Organ Transplantation, Institut national de la santé et de la recherche médicale, Unité mixte de recherche-S970, Paris, France; Division of Nephrology, Geneva University Hospitals, Geneva, Switzerland; Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
3
Department of Immunology and Histocompatibility, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
4
Paris Translational Research Center for Organ Transplantation, Institut national de la santé et de la recherche médicale, Unité mixte de recherche-S970, Paris, France; Department of Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
5
Department of Transplantation Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
6
Paris Translational Research Center for Organ Transplantation, Institut national de la santé et de la recherche médicale, Unité mixte de recherche-S970, Paris, France; Department of Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. Electronic address: alexandreloupy@gmail.com.
7
Paris Translational Research Center for Organ Transplantation, Institut national de la santé et de la recherche médicale, Unité mixte de recherche-S970, Paris, France; Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. Electronic address: carmen.lefaucheur@wanadoo.fr.

Abstract

A major hurdle to improving clinical care in the field of kidney transplantation is the lack of biomarkers of the response to antibody-mediated rejection (ABMR) treatment. To discover these we investigated the value of complement-binding donor-specific anti-HLA antibodies (DSAs) for evaluating the response to treatment. The study encompassed a prospective cohort of 139 kidney recipients with ABMR receiving the standard of care treatment, including plasma exchange, intravenous immunoglobulin and rituximab. Patients were systematically assessed at the time of diagnosis and three months after treatment initiation for clinical and allograft histological characteristics and anti-HLA DSAs, including their C1q-binding ability. After adjusting for clinical and histological parameters, post-treatment C1q-binding anti-HLA DSA was an independent and significant determinant of allograft loss (adjusted hazard ratio 2.57 (95% confidence interval 1.29-5.12). In 101 patients without post-treatment C1q-binding anti-HLA DSA there was a significantly improved glomerular filtration rate with significantly reduced glomerulitis, peritubular capillaritis, interstitial inflammation, tubulitis, C4d deposition, and endarteritis compared with 38 patients with posttreatment C1q-binding anti-HLA DSA. A conditional inference tree model identified five prognostic groups at the time of post-treatment evaluation based on glomerular filtration rate, presence of cg lesion and C1q-binding anti-HLA DSA (cross-validated accuracy: 0.77). Thus, circulating complement-binding anti-HLA DSAs are strong and independent predictors of allograft outcome after standard of care treatment in kidney recipients with ABMR.

KEYWORDS:

antibody-mediated rejection; complement-activating donor-specific anti-HLA antibody; kidney transplantation; response to treatment

PMID:
29801667
DOI:
10.1016/j.kint.2018.03.015
[Indexed for MEDLINE]

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