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

Jia Wang (1, 2, 3) , Zhao Cui (1, 2, 3) , Jie Lu (1, 2, 3) , Christian Probst (4) , Yi-Miao Zhang (1, 2, 3) , Xin Wang (1, 2, 3) , Zhen Qu (1, 2, 3) , Fang Wang (1, 2, 3) , Li-Qiang Meng (1, 2, 3) , Xu-Yang Cheng (1, 2, 3) , Gang Liu (1, 2, 3) , Hanna Debiec (5, 6) , Pierre Ronco (5, 6) , Ming-Hui Zhao (1, 2, 3, 7)

1 Renal Division [Beijing, China]
2 Key Laboratory of Renal Disease [Beijing, China]
3 Key Laboratory of CKD Prevention and Treatment [Beijing, China]
4 Institute of Experimental Immunology [Lubeck, Germany]
5 CHU Tenon [AP-HP]
6 Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation
7 Tsinghua-Peking Center for Life Sciences [Beijing, China]

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.

Mots clés: Biopsy; Autoimmunity; Anti-Idiotypic; Antibodies; 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

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]

Jia Wang, Zhao Cui, Jie Lu, Christian Probst, Yi-Miao Zhang, et al.. Circulating Antibodies against Thrombospondin Type-I Domain-Containing 7A in Chinese Patients with Idiopathic Membranous Nephropathy. Clinical Journal of the American Society of Nephrology, 2017, 12 (10), pp.1642-1651. ⟨10.2215/CJN.01460217⟩. ⟨inserm-02193806⟩