An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 Domain-Containing 7A-Specific Antibodies in Membranous Nephropathy

Thrombospondin type 1 domain-containing 7A (THSD7A) is a target antigen identified in adult membranous nephropathy (MN) along with the major antigen phospholipase A receptor 1 (PLA R1). The prevalence of THSD7A-Ab-positive patients is unknown, and it is unclear whether the clinical presentation diff...

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Published in:Journal of the American Society of Nephrology 2017-02, Vol.28 (2), p.520-531
Main Authors: Hoxha, Elion, Beck, Jr, Laurence H, Wiech, Thorsten, Tomas, Nicola M, Probst, Christian, Mindorf, Swantje, Meyer-Schwesinger, Catherine, Zahner, Gunther, Stahl, Phillip R, Schöpper, Ruth, Panzer, Ulf, Harendza, Sigrid, Helmchen, Udo, Salant, David J, Stahl, Rolf A K
Format: Article
Language:English
Subjects:
Adult
Autoantibodies - blood
Basic Research
Female
Fluorescent Antibody Technique, Indirect
Glomerulonephritis, Membranous - blood
Glomerulonephritis, Membranous - immunology
Humans
Male
Middle Aged
Prospective Studies
Retrospective Studies
Thrombospondins - immunology
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Summary:Thrombospondin type 1 domain-containing 7A (THSD7A) is a target antigen identified in adult membranous nephropathy (MN) along with the major antigen phospholipase A receptor 1 (PLA R1). The prevalence of THSD7A-Ab-positive patients is unknown, and it is unclear whether the clinical presentation differs between patients positive for PLA R1-Ab or THSD7A-Ab. We screened serum samples of 1276 patients with MN from three different cohorts for the presence of THSD7A-Ab by Western blot analysis and a newly developed indirect immunofluorescence test (IFT). Compared with Western blot analysis, the IFT had a 92% sensitivity and a 100% specificity. The prevalence of THSD7A-associated MN in a prospective cohort of 345 patients with MN was 2.6%, and most were women. In this cohort, the percentage of patients with THSD7A-associated MN and malignant disease significantly exceeded that of patients with PLA R1-associated MN and malignant disease. In all cohorts, we identified 40 patients with THSD7A-associated MN, eight of whom developed a malignancy within a median time of 3 months from diagnosis of MN. In one patient with THSD7A-associated MN and metastases of an endometrial carcinoma, immunohistochemistry showed THSD7A expression on the metastatic cells and within follicular dendritic cells of the metastasis-infiltrated lymph node. We conclude that the IFT allows sensitive and specific measurement of circulating THSD7A-Ab in patients with MN. Patients with THSD7A-associated MN differ in their clinical characteristics from patients with PLA R1-associated MN, and more intensive screening for the presence of malignancies may be warranted in those with THSD7A-associated MN.
ISSN:1046-6673
1533-3450
DOI:10.1681/asn.2016010050