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

Journal article
Authors C. Zaghrini
B. Seitz-Polski
J. Justino
G. Dolla
C. Payre
N. Jourde-Chiche
A. E. Van de Logt
C. Booth
E. Rigby
Jennie Lönnbro-Widgren
Jenny Nyström
C. Mariat
Z. Cui
J. F. M. Wetzels
G. Ghiggeri
L. H. Beck
P. Ronco
H. Debiec
G. Lambeau
Published in Kidney International
Volume 95
Issue 3
Pages 666-679
ISSN 0085-2538
Publication year 2019
Published at Institute of Medicine
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 666-679
Language en
Links dx.doi.org/10.1016/j.kint.2018.10.0...
Keywords clinical outcome, ELISA, malignancy, membranous nephropathy, sex, THSD7A, phospholipase a(2) receptor, anti-pla(2)r antibodies, pla2r, autoantibodies, glomerular-diseases, pregnancy, rituximab, subclass, deposits, outcomes, cancer, Urology & Nephrology, hieppati a, 1993, new england journal of medicine, v329, p85
Subject categories Urology and Nephrology

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.

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