title: The functional activities of complement factor H are impaired in patients with ANCA-positive vasculitis.
abstract: Increasing evidences have demonstrated that the activation of the alternative complement pathway is crucial for the pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Our recent study found that circulating levels of complement factor H (FH), a key regulator of the alternative pathway, were associated with disease activity. In the current study, functional activities of FH were assessed to further explore the potential role of FH in the pathogenesis of AAV. We found that the two patients with ANCA-negative pauci-immune necrotizing crescentic glomerulonephritis exhibited relatively normal functional activities of FH. However, patients with ANCA-positive vasculitis exhibited deficient functional activities of FH, in terms of interaction with and the regulation of C3b, binding to mCRP and endothelial cells, and the protection of host cells against complement attack. Our findings indicate that functional activities of FH are deficient in patients with ANCA-positive vasculitis, potentially contributing to the disease development.
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing 100034, China.
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Chen
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing 100034, China.
authors.forename: Feng-Mei
authors.initials: FM
authors.lastname: Wang
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing 100034, China.
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing 100034, China. Electronic address: yufengevert1@sina.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Yu
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing 100034, China. Electronic address: chenmin74@sina.com.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing 100034, China; Peking-Tsinghua Center for Life Sciences, Beijing 100034, China.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D017242:Complement Factor H / Q000276:immunology; D003170:Complement Pathway, Alternative / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; C493495:CFH protein, human; D017242:Complement Factor H; D003165:Complement System Proteins
keywords: ANCA; Complement; Factor H; Vasculitis