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Involvement of a tissue-specific autoantibody in skin disorders of murine systemic lupus erythematosus and autoinflammatory diseases.

Proc. Natl. Acad. Sci. U.S.A.2006 Feb 28;103(9):3292-7. Epub 2006 Feb 21
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摘要


Human systemic lupus erythematosus (SLE) and its murine model, MRL lpr/lpr mice, are well known to develop a wide range of symptoms, such as glomerulonephritis, dermatitis, and arthritis, as an immune-complex disease. However, the deposition of circulating immune complex does not fully explain the tissue specificity of disease. Tissue-specific autoantigens may also be involved in tissue inflammation. In this study, desmoglein 3 (Dsg3), a major component of epidermal desmosomes, was identified as a skin-specific autoantigen. Several murine models of skin inflammation were found to develop autoantibodies to Dsg3 tightly correlated with disease aggravation, especially in MRL lpr/lpr mice. Furthermore, SLE-prone skin disease-free FcgammaRIIb-deficient mice developed skin inflammation upon immunization with Dsg3. Taken together with histological studies, we concluded that skin-specific Dsg3 serves as an autoantigen in chronic skin inflammatory diseases accompanied by mast cell degranulation, including both murine SLE and other autoinflammatory diseases.

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