Idiopathic Dilated Cardiomyopathy : A Superantigen-Driven Autoimmune Disease

P. Luppi, W. A. Rudert, M. M. Zanone, G. Stassi, G. Trucco, D. Finegold, G. J. Boyle, P. D. Nido, F. X. McGowan, M. Trucco
1998 Circulation  
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 superantigentriggered 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
more » ... obtained from IDC patients who were undergoing heart transplantation. Infiltrating immune-cell phenotypes and gene expression of T-cell receptor (TCR) ␣and ␤-chain variable (V␣ and V␤) 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␤3, V␤7, and V␤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␤ families. The TCR V␣ 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. (Circulation. 1998;98:777-785.)
doi:10.1161/01.cir.98.8.777 pmid:9727548 fatcat:kypjmqqlxfh7xlwa5k5bgbdd4m