Novel ELISA for thrombospondin type 1 domain-containing 7A autoantibodies in membranous nephropathy - Archive ouverte HAL Access content directly
Journal Articles Kidney International Year : 2019

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

, (1) , , (1) , (2) , (3) , (4) , , , , , (5) , , (6) , (7) , (8) , (9) , (10) , (2)
1
2
3
4
5
6
7
8
9
10

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.
Fichier principal
Vignette du fichier
S0085253818308251.pdf (1.81 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

inserm-02193821 , version 1 (22-10-2021)

Licence

Attribution - NonCommercial - CC BY 4.0

Identifiers

Cite

Christelle Zaghrini, Barbara Seitz Seitz-Polski, Joana Justino, Guillaume Dolla, Christine Payre, et al.. Novel ELISA for thrombospondin type 1 domain-containing 7A autoantibodies in membranous nephropathy. Kidney International, 2019, 95 (3), pp.666-679. ⟨10.1016/j.kint.2018.10.024⟩. ⟨inserm-02193821⟩
102 View
89 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More