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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
Journal of the American Society of Nephrology, 02/2017, Letnik: 28, Številka: 2Journal Article
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.
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in: SICRIS
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