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

Clinical journal of the American Society of Nephrology: CJASN

Jia Wang¹ 

[1] *Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University;§Euroimmun Academy, Euroimmun Medical Diagnostics (China) Co., Ltd., Beijing, China;¶Department of Nephrology and Dialysis, Pierre and Marie Curie University, Paris Cedex 06, France;‖Institute of Experimental Immunology, Euroimmun Academy, Euroimmun Medical Diagnostics Co., Ltd Lubeck, Germany

关键词: glomerular disease;    Immunology and pathology;    membranous nephropathy;    Antibodies;    Antibodies, Anti-Idiotypic;    Autoimmunity;    Biopsy;    Fluorescent Antibody Technique;    Follow-Up Studies;    GN, Membranous;    Humans;    immunohistochemistry;    Kidney Glomerulus;    Neoplasms;    Prevalence;    proteinuria;    Receptors, Phospholipase A2;    Recurrence;    Thrombospondins;    United States;    PLA2R1 protein, human;   

DOI  :  10.2215/CJN.01460217

学科分类：泌尿医学

来源: American Society of Nephrology

【 摘 要 】

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.

【 授权许可】

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