title: The alternative pathway of complement activation may be involved in the renal damage of human anti-glomerular basement membrane disease.
abstract: Linear deposition of IgG and complement 3 (C3) along glomerular basement membrane (GBM) is generally revealed in the kidneys of human anti-GBM disease. Our recent studies demonstrated the pathogenic role of complement activation in renal damage of this disease. However, the pathways of complement activation were still paradoxical. In this study, renal biopsy tissues from 10 patients with anti-GBM disease were used to investigate the pathways of complement activation by detecting the deposition of various complement components, including C1q, factor B, factor P (properdin), mannose-binding lectin (MBL), C3d, C4d and C5b-9, using immunohistochemistry and immunofluorescence. We found that C1q, factor B, properdin, C3d, C4d and C5b-9 were detected in all the glomeruli of our patients, along GBM with a linear and/or granular staining pattern. Furthermore, C1q, factor B and properdin co-localized well with C5b-9. The properdin also co-localized well with C3d. However, the deposition of MBL was diffusive in mesangium, GBM, Bowman's capsule and within crescents and was not co-localized with C5b-9 but partially co-localized with C4d. The intensity of factor B deposition (3.3 vs. 1.2, P<0.001) and C5b-9 deposition (3.2 vs. 1.6, P<0.001) was significantly stronger in the glomeruli with crescent formation, compared with the glomeruli without crescents. The complement system is overall activated via both the alternative pathway and classical pathway in the kidneys of human anti-GBM disease. The alternative pathway might play an important role in complement activation induced renal damage.
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China; Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ma
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China.
authors.forename: Shui-Yi
authors.initials: SY
authors.lastname: Hu
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Jia
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ao
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
authors.forename: Yun-Hua
authors.initials: YH
authors.lastname: Liao
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education of China, Beijing, China; Peking-Tsinghua Center for Life Sciences, Beijing, China.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D019867:Anti-Glomerular Basement Membrane Disease / Q000378:metabolism / Q000473:pathology*; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged
chemical_list: D003176:Complement C3; D007074:Immunoglobulin G