From the Divisions of Immunogenetics (P.L., W.A.R., M.M.Z., G.S., M.T.),
Endocrinology (D.F.), and Cardiology (G.J.B.), Department of Pediatrics, and
the Department of Pathology (G.T.), University of Pittsburgh School of
Medicine and Children's Hospital, Pittsburgh, Pa; and the Department of
Cardiac Surgery, Harvard Medical School and Children's Hospital
(P.D.N.), and the Department of Anesthesiology, Harvard Medical School and
Anesthesia/Critical Care Medicine Laboratories, Children's Hospital
(F.X.M.), Boston, Mass.
Correspondence to Massimo Trucco, MD, Children's Hospital of Pittsburgh, Rangos Research Center, 3705 Fifth Ave at DeSoto St, Pittsburgh, PA 15213.
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)
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.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Idiopathic Dilated Cardiomyopathy
A Superantigen-Driven Autoimmune Disease
- and ß-chain variable
(V and Vß) 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 Vß3, Vß7, and Vß13.1 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 Vß families. The TCR V
repertoire was never found to be skewed.
Key Words: cardiomyopathy • immunology • myocarditis • viruses
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