title: An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 Domain-Containing 7A-Specific Antibodies in Membranous Nephropathy.
abstract: Thrombospondin type 1 domain-containing 7A (THSD7A) is a target antigen identified in adult membranous nephropathy (MN) along with the major antigen phospholipase A2receptor 1 (PLA2R1). The prevalence of THSD7A-Ab-positive patients is unknown, and it is unclear whether the clinical presentation differs between patients positive for PLA2R1-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 PLA2R1-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 PLA2R1-associated MN, and more intensive screening for the presence of malignancies may be warranted in those with THSD7A-associated MN.
authors.affiliation: III Medizinische Klinik.
authors.forename: Elion
authors.initials: E
authors.lastname: Hoxha
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts; and.
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Beck
authors.affiliation: Institut für Pathologie, and.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wiech
authors.affiliation: III Medizinische Klinik.
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Tomas
authors.affiliation: Institute of Experimental Immunology, Euroimmun AG, Lubeck, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Probst
authors.affiliation: Institute of Experimental Immunology, Euroimmun AG, Lubeck, Germany.
authors.forename: Swantje
authors.initials: S
authors.lastname: Mindorf
authors.affiliation: III Medizinische Klinik.
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyer-Schwesinger
authors.affiliation: III Medizinische Klinik.
authors.forename: Gunther
authors.initials: G
authors.lastname: Zahner
authors.affiliation: Institut für Pathologie, and.
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Stahl
authors.affiliation: III Medizinische Klinik.
authors.forename: Ruth
authors.initials: R
authors.lastname: Schöpper
authors.affiliation: III Medizinische Klinik.
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
authors.affiliation: III Medizinische Klinik.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Harendza
authors.affiliation: Nierenregister, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Helmchen
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts; and.
authors.forename: David J
authors.initials: DJ
authors.lastname: Salant
authors.affiliation: III Medizinische Klinik, rstahl@uke.de.
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015433:Glomerulonephritis, Membranous / Q000097:blood* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D019699:Thrombospondins / Q000276:immunology*
chemical_list: D001323:Autoantibodies; C546399:THSD7A protein, human; D019699:Thrombospondins
keywords: THSD7A Antibodies; membranous nephropathy; nephrotic syndrome