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学科主题: 临床医学
题名:
New advances in the pathogenesis of ANCA-associated vasculitides
作者: Chen, M.1,2; Kallenberg, C. G. M.1
关键词: ANCA ; vasculitis ; pathogenesis
刊名: CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
发表日期: 2009
卷: 27, 期:1, 页:S108-S114
收录类别: SCI
文章类型: Review
WOS标题词: Science & Technology
类目[WOS]: Rheumatology
研究领域[WOS]: Rheumatology
关键词[WOS]: ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES ; SMALL-VESSEL VASCULITIS ; INTERACTIONS IN-VIVO ; WEGENERS-GRANULOMATOSIS ; ANTIMYELOPEROXIDASE ANTIBODIES ; MEMBRANE PROTEINASE-3 ; SYSTEMIC VASCULITIS ; ENDOTHELIAL-CELLS ; DISEASE-ACTIVITY ; T-CELLS
英文摘要:

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of autoimmune disorders including Wegener granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS) and renal-limited vasculitis (RLV). This paper reviews updated information on the pathogenesis of AAV Additional clinical evidence for a pathogenic role of ANCA comes from the observation that patients with severe acute renal failure treated with plasma exchange had a lower risk for progression to end-stage renal disease than patients who received intravenous methylprednisolone therapy, both in addition to standard treatment. Recent data also suggest that antibodies to complementary proteinase-3 (cPR3), probably cross-reacting with plasminogen, may induce PR3-ANCA. Furthermore, a new ANCA, directed against human lysosome membrane protein-2 (LAMP-2), concurrent with PR3-ANCA or MPO-ANCA, was described as a sensitive and specific marker for renal AAV In vitro, ANCA can further activate printed neutrophils to release reactive oxygen species and lytic enzymes, and, in conjunction with neutrophils, damage and lyse endothelial cells. In vivo, tran, fer of splenocytes from myeloperoxidase-deficient mice immunized with mouse myeloperoxidase into wild-type mice resulted in pauci-immune systemic vasculitis. A similar experiment in PR3-deficient mice did not cause significant vasculitic lesions. In the anti-MPO induced vasculitis mouse model, a critical role of complement activation was suggested. The anti- LAMP-2 antibody can also induce pauci-immune necrotizing crescentic glomerulonephritis in rats. Rats developed both cross-reactive antibodies to LAMP-2 and crescentic glomerulonephritis when immunized with FimH, an adhesin from Gram-negative bacteria which has strong homology with human LAMP-2. Together, clinical, in vitro and in vivo data support a pathogenic role for ANCA in AAV, although this role is more evident for myeloperoxidase-ANCA than for PR3-ANCA. The role of anti- LAMP-2 requires further studies.

语种: 英语
WOS记录号: WOS:000269513400019
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50779
Appears in Collections:北京大学第一临床医学院_肾脏内科_期刊论文

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作者单位: 1.Peking Univ, Hosp 1, Div Renal, Beijing 100034, Peoples R China
2.Univ Groningen, Dept Rheumatol & Clin Immunol, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands

Recommended Citation:
Chen, M.,Kallenberg, C. G. M.. New advances in the pathogenesis of ANCA-associated vasculitides[J]. CLINICAL AND EXPERIMENTAL RHEUMATOLOGY,2009,27(1):S108-S114.
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