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

Abstract

BACKGROUND AND OBJECTIVES:

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.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:

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.

RESULTS:

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.

CONCLUSIONS:

THSD7A-associated membranous nephropathy has a low prevalence in Chinese patients. The double-positive patients suggest dual autoimmune responses.

• Authors: Jia Wang, Zhao Cui, Jie Lu, Christian Probst, Yi-Miao Zhang, Xin Wang, Zhen Qu, Fang Wang, Li-Qiang Meng, Xu-Yang Cheng, Gang Liu, Hanna Debiec, Pierre Ronco, Ming-Hui Zhao
• Journal: Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 12 Issue 10 Pg. 1642-1651 (Oct 06 2017) ISSN: 1555-905X [Electronic] United States
• PMID: 28801527 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 by the American Society of Nephrology.

Chemical References

• Autoantibodies
• Receptors, Phospholipase A2
• THSD7A protein, human
• Thrombospondins

Topics

• Adult
• Aged
• Asian People
• Autoantibodies (blood)
• Biopsy
• China (epidemiology)
• Female
• Fluorescent Antibody Technique
• Glomerulonephritis, Membranous (blood, diagnosis, ethnology, immunology)
• Humans
• Kidney Glomerulus (immunology, pathology)
• Male
• Middle Aged
• Prevalence
• Receptors, Phospholipase A2 (immunology)
• Retrospective Studies
• Thrombospondins (immunology)
• Young Adult