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

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.

• Authors: Shigeo Hara, Takahiro Tsuji, Yuichiro Fukasawa, Satoshi Hisano, Satoshi Morito, Toshiki Hyodo, Shunsuke Goto, Shinichi Nishi, Akihiro Yoshimoto, Tomoo Itoh
• Journal: Virchows Archiv : an international journal of pathology (Virchows Arch) Vol. 474 Issue 6 Pg. 735-743 (Jun 2019) ISSN: 1432-2307 [Electronic] Germany
• PMID: 30868298 (Publication Type: Journal Article)

Chemical References

• Autoantibodies
• THSD7A protein, human
• Thrombospondins

Topics

• Autoantibodies (immunology)
• Female
• Fluorescent Antibody Technique (methods)
• Glomerulonephritis, Membranous (diagnosis, epidemiology, pathology)
• Humans
• Immunohistochemistry (methods)
• Incidence
• Middle Aged
• Prevalence
• Risk Factors
• Thrombospondins (immunology, metabolism)