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Kidney Int. 2019 Mar;95(3):666-679. doi: 10.1016/j.kint.2018.10.024.

Novel ELISA for thrombospondin type 1 domain-containing 7A autoantibodies in membranous nephropathy.

Author information

1
Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 Valbonne Sophia Antipolis, France.
2
Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 Valbonne Sophia Antipolis, France; Laboratoire d'Immunologie, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice, France; Service de Néphrologie, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice, France.
3
Aix-Marseille Université, Centre Recherche en Cardiovasculaire et Nutrition, Institut National de la Recherche Agronomique 1260, Institut National de la Santé et de la Recherche Médicale 1263, Marseille, France; Assistance Publique-Hôpitaux de Marseille, Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, Marseille, France.
4
Department of Nephrology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
5
Evelina London Children's Hospital, Lambeth, London, United Kingdom.
6
Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
7
Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
8
Service de Néphrologie Dialyse, Transplantation Rénale, Hôpital Nord, Lyon, France; CHU de Saint-Etienne, GIMAP, EA 3065, Université Jean Monnet, Saint-Etienne, Comue Université de Lyon, Lyon, France.
9
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
10
Division of Nephrology, Dialysis and Transplantation, Laboratory of Molecular Nephrology, G. Gaslini Children Hospital, Genoa, Italy.
11
Renal Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
12
Sorbonne Université, Université Pierre et Marie Curie, Université Paris 6, Paris, France; Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche_S1155, Paris, France; Service de Néphrologie et Dialyses, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France.
13
Sorbonne Université, Université Pierre et Marie Curie, Université Paris 6, Paris, France; Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche_S1155, Paris, France.
14
Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 Valbonne Sophia Antipolis, France. Electronic address: lambeau@ipmc.cnrs.fr.

Abstract

Autoantibodies against phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type 1 domain-containing 7A (THSD7A) are emerging as biomarkers to classify membranous nephropathy (MN) and to predict outcome or response to treatment. Anti-THSD7A autoantibodies are detected by Western blot and indirect immunofluorescence test (IIFT). Here, we developed a sensitive enzyme-linked immunosorbent assay (ELISA) optimized for quantitative detection of anti-THSD7A autoantibodies. Among 1012 biopsy-proven MN patients from 6 cohorts, 28 THSD7A-positive patients were identified by ELISA, indicating a prevalence of 2.8%. By screening additional patients, mostly referred because of PLA2R1-unrelated MN, we identified 21 more cases, establishing a cohort of 49 THSD7A-positive patients. Twenty-eight patients (57%) were male, and male patients were older than female patients (67 versus 49 years). Eight patients had a history of malignancy, but only 3 were diagnosed with malignancy within 2 years of MN diagnosis. We compared the results of ELISA, IIFT, Western blot, and biopsy staining, and found a significant correlation between ELISA and IIFT titers. Anti-THSD7A autoantibodies were predominantly IgG4 in all patients. Eight patients were double positive for THSD7A and PLA2R1. Levels of anti-THSD7A autoantibodies correlated with disease activity and with response to treatment. Patients with high titer at baseline had poor clinical outcome. In a subgroup of patients with serial titers, persistently elevated anti-THSD7A autoantibodies were observed in patients who did not respond to treatment or did not achieve remission. We conclude that the novel anti-THSD7A ELISA can be used to identify patients with THSD7A-associated MN and to monitor autoantibody titers during treatment.

KEYWORDS:

ELISA; THSD7A; clinical outcome; malignancy; membranous nephropathy; sex

PMID:
30784662
DOI:
10.1016/j.kint.2018.10.024
[Indexed for MEDLINE]

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