Coxsackievirus B3 infection induces anti-flavoprotein antibodies in mice

Enteroviruses, the most common cause of acute myocarditis, are also suppose d aetiological agents of dilated cardiomyopathy. Autoantibodies (anti-M7; K lein & Berg, Clin Exp Immunol 1990; 58:283-92) directed against flavoprotei ns with covalently bound flavin (alpha Fp-Ab; Otto et al., Clin Exp Immunol 1998; 111:541-2) are detected in up to 30% of sera of patients with myocar ditis and idiopathic dilated cardiomyopathy (IDCM). Mice inoculated with a myocarditic variant of coxsackievirus B3 (CVB3) were employed to study the occurrence of serum alpha Fp-Ab following viral infection. The presence of alpha Fp-Ab was analysed by Western blotting with the flavoprotein antigens 6-hydroxy-d-nicotine oxidase (6HDNO) and sarcosine oxidase (SaO). Of 10 se ra from CVB3-infected mice, five showed a strong reaction with both antigen s. The sera were reactive also to the mitochondrial covalently flavinylated proteins dimethylglycine dehydrogenase and sarcosine dehydrogenase. Sera o f non-infected mice did not react with these antigens. A 6HDNO mutant prote in with non-covalently bound FAD no longer reacted on Western blots with se ra of CVB3-infected mice. Preincubation with FAD abolished or reduced the r eaction of the sera with the 6HDNO antigen. At 2 weeks p.i. the alpha Fp-Ab were of the IgM and IgG isotypes, at 7 and 9 weeks p.i. of the IgG isotype . The sera of CVB3-infected mice reproduced closely the antigenic specifici ty of the anti-M7 sera of patients, lending further support to the role of coxsackieviruses in the pathogenesis of IDCM.