Identification of autoantibodies with the corresponding antigen for repetitive coxsackievirus infection-induced cardiomyopathy.
BACKGROUND
The hypothesis that viral myocarditis causes an autoimmune response and subsequent dilated cardiomyopathy is controversial. To further investigate the autoimmune mechanism of cardiac dilatation and dysfunction after repeated episodes of viral myocarditis, the cardiac autoantigens induced by repetitive coxsackievirus B3 (CVB3) infection were examined.


RESULTS
Male inbred A/J mice were inoculated intraperitoneally with CVB3 at 3 and 40 weeks of age. At 8 weeks after the second inoculation, the mortality of the repetitive CVB3 group was significantly increased compared with that of the control group, and was associated with a significant reduction in fractional shortening and marked left ventricular dilatation without inflammatory cell infiltration. The cardiac antigens in the repetitive CVB3 infection were identified by 2-dimensional electrophoresis and subsequent liquid chromatography/tandem mass spectrometry (LC-MS/MS) using the serum at 2 weeks after the second inoculation. LC-MS/MS and immunohistochemistry demonstrated alpha-cardiac actin and heat shock protein 60 (HSP60) as cardiac near-surface antigens induced by the repetitive CVB3 infection. Immunoelectron microscopy disclosed the selective localization of anti-IgM antibody on the membrane of the myocytes in the repetitive CVB3 group.


CONCLUSIONS
IgM antibodies against alpha-cardiac actin and HSP60, which were induced by repetitive CVB3 infection, may play an important role in the pathophysiology of the subsequent cardiac dysfunction and dilatation.
Takata
Satoko
S
Department of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
Nakamura
Hiroshi
H
Umemoto
Seiji
S
Yamaguchil
Kazuhito
K
Sekine
Taichi
T
Kato
Tomohiro
T
Nishioka
Kusuki
K
Matsuzaki
Masunori
M
D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001835:Body Weight; D009202:Cardiomyopathies / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004770:Enterovirus / Q000276:immunology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A
D001323:Autoantibodies