The Alternative Pathway of Complement Activation is Critical for Blister Induction in Experimental Epidermolysis Bullosa Acquisita.
From: Department of Dermatology, University of Lübeck, Lübeck, Germany, and Department of Pediatrics, Laboratory of Developmental Immunology, Massachusetts General Hospital, Boston 02115, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: May 2007
- ISSN: 0022-1767
- Volume: 178
- Issue: 10
- Pages: 6514-21
- Medium: Print
- Language: English
- Citation (JAMA): Mihai Sidonia, Chiriac Mircea T, Takahashi Kazue, et al. The Alternative Pathway of Complement Activation is Critical for Blister Induction in Experimental Epidermolysis Bullosa Acquisita.. J. Immunol. May 2007;178:6514-21
Abstract
Epidermolysis bullosa acquisita is a subepidermal blistering disease associated with tissue-bound and circulating autoantibodies against type VII collagen, a major constituent of the dermal-epidermal junction. The passive transfer of Abs against type VII collagen into mice induces a subepidermal blistering disease dependent upon activation of terminal complement components. To further dissect the role of the different complement activation pathways in this model, we injected C1q-deficient, mannan-binding lectin-deficient, and factor B-deficient mice with rabbit Abs against murine type VII collagen. The development and evolution of blistering had a similar pattern in mannan-binding lectin-deficient and control mice and was initially only marginally less extensive in C1q-deficient mice compared with controls. Importantly, factor B-deficient mice developed a delayed and significantly less severe blistering disease compared with factor B-sufficient mice. A significantly lower neutrophilic infiltration was observed in factor B-deficient mice compared with controls and local reconstitution with granulocytes restored the blistering disease in factor B-deficient mice. Our study provides the first direct evidence for the involvement of the alternative pathway in an autoantibody-induced blistering disease and should facilitate the development of new therapeutic strategies for epidermolysis bullosa acquisita and related autoimmune diseases.
Mesh Headings (Keywords): Animals, Autoantibodies, Blister, Collagen Type VII, Complement C1q, Complement Pathway, Alternative, Epidermolysis Bullosa Acquisita, Genetic Predisposition to Disease, Immunoglobulin G, Mannose-Binding Lectin, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout
Check for Full Text / PubMed Unique Identifier (PMID): 17475881
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