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Complement Activation Is Involved in Renal Damage in Human Antineutrophil Cytoplasmic Autoantibody Associated Pauci-Immune Vasculitis

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Abstract

Objective

This study was to investigate the evidence for complement activation in renal biopsy specimens of patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune vasculitis.

Methods

Renal biopsy specimens from seven patients with MPO-ANCA positive pauci-immune necrotizing crescentic glomerulonephritis (NCGN) were used to detect the staining of membrane attack complex (MAC), C3d, C4d, mannose-binding lectin (MBL), factor B and factor P using immunohistochemistry and immunofluorescence. Renal tissue from seven patients with minimal change disease (MCD) and two normal renal tissue were used as controls.

Results

MAC, C3d, factor B and factor P could be detected in glomeruli and small blood vessels with active vasculitis of patients with pauci-immune AAV, but not or scarcely in patients with MCD and in normal renal tissue. C3d and factor B co-localized with MAC, factor P colocalized with C3d. MBL and C4d were not detected in patients with AAV.

Conclusion

The alternative pathway of the complement system is involved in renal damage of human pauci-immune AAV.

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Abbreviations

ANCA:

antineutrophil cytoplasmic autoantibody

AAV:

ANCA-associated vasculitis

MPO:

myeloperoxidase

MBL:

mannose-binding lectin

MAC:

membrane attack complex

MCD:

minimal change disease

NCGN:

necrotizing crescentic glomerulonephritis

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Acknowledgements

This study is supported by a grant from National Science Fund for Distinguished Young Scholars (No.30725034) and a grant of the Chinese 985 project (985-2-104-113). P. Heeringa is supported by a grant from the Dutch Organization for Scientific research (NWO VIDI 917.66.342) and by a grant from the Dutch Kidney Foundation (PC 07-2204).

We are very grateful to Dr. Wan-zhong Zou and Dr. Chen Wang for assistance in the scoring and collecting pathological data of the patients.

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Authors and Affiliations

  1. Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, 100034, China

    Guang-qun Xing, Min Chen, Gang Liu, Jun-jun Zhang, Xin Zheng, Jie E & Ming-hui Zhao

  2. Department of Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands

    Cees G. M. Kallenberg

  3. Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands

    Peter Heeringa

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  1. Guang-qun Xing
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  2. Min Chen
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Correspondence to Ming-hui Zhao.

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Xing, Gq., Chen, M., Liu, G. et al. Complement Activation Is Involved in Renal Damage in Human Antineutrophil Cytoplasmic Autoantibody Associated Pauci-Immune Vasculitis. J Clin Immunol 29, 282–291 (2009). https://doi.org/10.1007/s10875-008-9268-2

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  • DOI: https://doi.org/10.1007/s10875-008-9268-2

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