Clinicopathological characteristics of thrombospondin type 1 domain-containing 7A-associated membranous nephropathy.

Content Provider	Europe PMC
Author	Hara, Shigeo Tsuji, Takahiro Fukasawa, Yuichiro Hisano, Satoshi Morito, Satoshi Hyodo, Toshiki Goto, Shunsuke Nishi, Shinichi Yoshimoto, Akihiro Itoh, Tomoo
Abstract	Thrombospondin type 1 domain-containing 7A (THSD7A) is a recently identified target antigen of idiopathic membranous nephropathy (iMN). The clinicopathological characteristics of THSD7A-associated MN are poorly characterised due to low prevalence among MN patients. Among 469 consecutive cases of pathologically confirmed MN diagnosed at four centres in Japan, 14 cases were confirmed positive for THSD7A by immunohistochemistry (3.0%). The prevalence of THSD7A-associated MN tended to be higher in northern Japan. Most cases demonstrated nephrotic-range proteinuria (12/14 cases, 86%). In two patients, cancer was detected at the time of renal biopsy (small-cell carcinoma of the lung and prostatic adenocarcinoma with neuroendocrine differentiation). Both tumours were negative for THSD7A. Four patients had concurrent or previous incidence of allergic diseases, including one patient with Kimura’s disease. Pathological analysis of kidney biopsy tissue revealed slight mesangial cell proliferation in three cases and spike formation in one case. Immunofluorescence studies demonstrated that IgG subclass was mainly IgG4-dominant/codominant (12/13, 92% cases), while the case with prostatic cancer had an IgG2-dominant distribution. The immunostaining profile for components of the lectin complement pathways was not significant in three cases including two patients with malignancy. One case was dual positive for THSD7A and PLA2R. Of 10 cases with known clinical follow-up data, 6 demonstrated reduced serum creatinine and 8 presented reduced proteinuria. In summary, although the major IgG phenotype was usually IgG4-dominant/codominant, clinical background was otherwise heterogeneous. Further investigation of regional differences in THSD7A-associated MN prevalence may reveal genetic and environmental risk factor and associated pathogenic mechanisms.Electronic supplementary materialThe online version of this article (10.1007/s00428-019-02558-0) contains supplementary material, which is available to authorized users.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6581930&blobtype=pdf
ISSN	09456317
Journal	Virchows Archiv [Virchows Arch]
Volume Number	474
DOI	10.1007/s00428-019-02558-0
PubMed Central reference number	PMC6581930
Issue Number	6
PubMed reference number	30868298
e-ISSN	14322307
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2019-03-14
Publisher Place	Berlin/Heidelberg
Access Restriction	Open
Rights License	Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. © The Author(s) 2019
Subject Keyword	Allergic disorder IgG subclass Malignancy Membranous nephropathy THSD7A
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Pathology and Forensic Medicine