Idiopathic dilated cardiomyopathy - A superantigen-driven autoimmune disease

Article

关键词: POLYMERASE CHAIN-REACTION;    DEPENDENT DIABETES-MELLITUS;    TUMOR-INFILTRATING LYMPHOCYTES;    T-CELLS;    MYOCARDIAL BIOPSIES;    ENTEROVIRAL RNA;    VIRUS;    GENE;    MICE;    STIMULATION;   

DOI  :  10.1161/01.CIR.98.8.777

来源: SCIE

【 摘 要 】

Background-Many cases of idiopathic dilated cardiomyopathy (IDC) result from an inflammatory myocarditis. The specific immunological mechanisms are not yet defined. Various autoimmune diseases are associated with superantigen-triggered immune responses, resulting in massive T-cell activation and tissue damage. We studied 3 cases in a search for evidence that such a phenomenon is also implicated in IDC. Methods and Results-Myocardial, lymph node, and thymic tissue samples were obtained from IDC patients who were undergoing heart transplantation. Infiltrating immune-cell phenotypes and gene expression of T-cell receptor (TCR) alpha- and beta-chain variable (V alpha and V beta) regions were analyzed by immunostaining and polymerase chain reaction. Similar technical approaches were used to assay the tissues for the presence of coxsackievirus B (CVB), In all the specimens analyzed, an overexpression of the TCR V beta 3, V beta 7, and V beta 13.1 gene families was detected among the infiltrating T cells. These tissues were also found to be CVB3-positive. In vitro exposure of peripheral blood mononuclear cells to lysates of cells infected with CVB3 was capable of stimulating expansion of the same TCR V beta families, The TCR V alpha repertoire was never found to be skewed. Conclusions-A superantigen-mediated immune response is involved in human heart disease. CVB3 may directly or indirectly trigger this response, suggesting a possible mechanistic link between CVB infection and myocarditis development progressing to IDC.

【 授权许可】

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