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

Clin J Am Soc Nephrol. 2017 Oct 6;12(10):1642-1651. doi: 10.2215/CJN.01460217. Epub 2017 Aug 11.

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.

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

MeSH terms

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

Substances

  • Autoantibodies
  • Receptors, Phospholipase A2
  • Thrombospondins
  • thrombospondin type I domain containing 7A protein, human