Coxsackievirus B3 infection induces anti-flavoprotein antibodies in mice.

Abstract

Enteroviruses, the most common cause of acute myocarditis, are also supposed aetiological agents of dilated cardiomyopathy. Autoantibodies (anti-M7; Klein & Berg, Clin Exp Immunol 1990; 58:283-92) directed against flavoproteins with covalently bound flavin (alphaFp-Ab; Otto et al., Clin Exp Immunol 1998; 111:541-2) are detected in up to 30% of sera of patients with myocarditis and idiopathic dilated cardiomyopathy (IDCM). Mice inoculated with a myocarditic variant of coxsackievirus B3 (CVB3) were employed to study the occurrence of serum alphaFp-Ab following viral infection. The presence of alphaFp-Ab was analysed by Western blotting with the flavoprotein antigens 6-hydroxy-D-nicotine oxidase (6HDNO) and sarcosine oxidase (SaO). Of 10 sera from CVB3-infected mice, five showed a strong reaction with both antigens. The sera were reactive also to the mitochondrial covalently flavinylated proteins dimethylglycine dehydrogenase and sarcosine dehydrogenase. Sera of non-infected mice did not react with these antigens. A 6HDNO mutant protein with non-covalently bound FAD no longer reacted on Western blots with sera of CVB3-infected mice. Preincubation with FAD abolished or reduced the reaction of the sera with the 6HDNO antigen. At 2 weeks p.i. the alphaFp-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 specificity of the anti-M7 sera of patients, lending further support to the role of coxsackieviruses in the pathogenesis of IDCM.

• Authors: G Cicek, T Vuorinen, I Stähle, P Stepanek, N Freudenberg, R Brandsch
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 122 Issue 3 Pg. 404-9 (Dec 2000) ISSN: 0009-9104 [Print] England
• PMID: 11122247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Flavoproteins
• Immunoglobulin G
• Immunoglobulin M
• Peptides
• Flavin-Adenine Dinucleotide
• Oxidoreductases
• Oxidoreductases, N-Demethylating
• Sarcosine Oxidase
• 6-hydroxy-D-nicotine oxidase
• Trypsin
• Metalloendopeptidases
• peptidyl-Lys metalloendopeptidase

Topics

• Animals
• Autoantibodies (immunology)
• Cardiomyopathy, Dilated (blood, immunology, pathology)
• Coxsackievirus Infections (blood, immunology, pathology)
• Disease Models, Animal
• Enterovirus B, Human (immunology)
• Flavin-Adenine Dinucleotide (immunology)
• Flavoproteins (immunology)
• Humans
• Immunoglobulin G (blood, immunology)
• Immunoglobulin M (blood, immunology)
• Male
• Metalloendopeptidases (metabolism)
• Mice
• Mitochondria, Liver (metabolism)
• Myocarditis (blood, immunology, pathology)
• Myocardium (pathology)
• Neutralization Tests
• Oxidoreductases (immunology)
• Oxidoreductases, N-Demethylating (immunology)
• Peptides (immunology)
• Rats
• Sarcosine Oxidase
• Trypsin (metabolism)