| Pathophysiology of ANCA-associated small vessel vasculitis. | |
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MedLine Citation:
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PMID: 20878509 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Antineutrophil cytoplasmic autoantibodies (ANCAs) directed to proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) are strongly associated with the ANCA-associated vasculitides--Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Clinical observations, including the efficacy of B-cell depletion via rituximab treatment, support--but do not prove--a pathogenic role for ANCA in the ANCA-associated vasculitides. In vitro experimental studies show that the interplay of ANCA, neutrophils, the alternative pathway of the complement system, and endothelial cells could result in lysis of the endothelium. A pathogenic role for MPO-ANCA is strongly supported by in vivo experimental studies in mice and rats, which also elucidate the pathogenic mechanisms involved in lesion development. Unfortunately, an animal model for PR3-ANCA-associated Wegener's granulomatosis is not yet available. Here, cellular immunity appears to play a major role as well, particularly via interleukin-17-producing T cells, in line with granulomatous inflammation in the lesions. Finally, microbial factors, in particular Staphylococcus aureus and gram-negative bacteria, seem to be involved in disease induction and expression, but further studies are needed to define their precise role in disease development. |
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Authors:
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Cees G M Kallenberg |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Current rheumatology reports Volume: 12 ISSN: 1534-6307 ISO Abbreviation: Curr Rheumatol Rep Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-10-05 Completed Date: 2011-01-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100888970 Medline TA: Curr Rheumatol Rep Country: United States |
Other Details:
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Languages: eng Pagination: 399-405 Citation Subset: IM |
Affiliation:
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Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, AA21, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. c.g.m.kallenberg@reuma.umcg.nl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Antineutrophil Cytoplasmic / blood* Cells, Cultured Disease Models, Animal Humans Immunity, Cellular / immunology Mice Microscopic Polyangiitis / immunology, pathology, physiopathology* Myeloblastin / immunology Neutrophils / cytology, immunology Peroxidase / immunology Rats Staphylococcus aureus / immunology, pathogenicity Th17 Cells / immunology |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Antineutrophil Cytoplasmic; EC 1.11.1.7/Peroxidase; EC 3.4.21.76/Myeloblastin |
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