Circulating Antibodies against Thrombospondin Type-I Domain-Containing 7A in Chinese Patients with Idiopathic Membranous Nephropathy

• Published in: Clinical journal of the American Society of Nephrology 2017-10, Vol.12 (10), p.1642-1651
• Main Authors: Wang, Jia, Cui, Zhao, Lu, Jie, Probst, Christian, Zhang, Yi-Miao, Wang, Xin, Qu, Zhen, Wang, Fang, Meng, Li-Qiang, Cheng, Xu-Yang, Liu, Gang, Debiec, Hanna, Ronco, Pierre, Zhao, Ming-Hui
• Format: Article
• Language: English
• Subjects: Adult; Aged; Asian People; Autoantibodies - blood; Biochemistry, Molecular Biology; Biopsy; China - epidemiology; Female; Fluorescent Antibody Technique; Genomics; Glomerulonephritis, Membranous - blood; Glomerulonephritis, Membranous - diagnosis; Glomerulonephritis, Membranous - ethnology; Glomerulonephritis, Membranous - immunology; Humans; Kidney Glomerulus - immunology; Kidney Glomerulus - pathology; Life Sciences; Male; Middle Aged; Original; Prevalence; Receptors, Phospholipase A2 - immunology; Retrospective Studies; Thrombospondins - immunology; Young Adult
• ISSN: 1555-9041; 1555-905X
• DOI: 10.2215/CJN.01460217

Thrombospondin type-I domain-containing 7A (THSD7A) was recently identified as the target antigen in about 10% of patients with M-type phospholipase A2 receptor (PLA2R)-negative membranous nephropathy in European and North American populations. The prevalence of THSD7A in other populations and their clinical associations deserve further clarification. Immunofluorescence assay was performed to investigate anti-THSD7A antibodies in 578 consecutive patients with biopsy-proven idiopathic membranous nephropathy, 114 patients with secondary membranous nephropathy, 64 disease controls, and 20 healthy controls. Glomerular expression of THSD7A antigen was examined by immunohistochemistry. Anti-PLA2R antibodies and glomerular PLA2R expression were also screened. Among the 578 patients with idiopathic membranous nephropathy, 12 (2%) patients were identified as THSD7A-positive: ten patients were THSD7A-positive alone, which accounted for 16% (ten of 64) of PLA2R-negative patients; two patients were dual-positive for both anti-THSD7A and anti-PLA2R antibodies and showed enhanced expression of both antigens colocalized in glomeruli. Among the 114 patients with secondary membranous nephropathy, one among 44 (2%) patients with cancer had anti-THSD7A antibodies, whereas 18 of 44 (41%) had anti-PLA2R antibodies. No anti-THSD7A antibody was detected in other disease controls or healthy individuals. Clinical features were comparable between the patients with and without THSD7A. During follow-up, two patients who achieved remission had a clearance of circulating antibodies against THSD7A, whereas antibodies increased in parallel with proteinuria in a patient with a relapse. THSD7A-associated membranous nephropathy has a low prevalence in Chinese patients. The double-positive patients suggest dual autoimmune responses.