Coxsackievirus B1-induced chronic inflammatory myopathy: differences in induction of autoantibodies to muscle and nuclear antigens by cloned myopathic and amyopathic viruses.
Infection of susceptible strains of mice with the myopathic Tucson strain of coxsackievirus B1 (CVB1(T)) leads to the development of chronic inflammatory myopathy (CIM). The underlying mechanism of CIM appears to be immunopathic, but it is not known whether autoimmunity is involved. The objectives of this study were to determine whether autoantibodies are produced and whether they correlate with the pathology of CIM. Mice were infected with either a myopathic (MP1.23 or MP1.24) or an amyopathic (AMP2.17) CVB1(T) cloned virus. The two myopathic (MP) viruses cause CIM, whereas the amyopathic (AMP) virus, derived from a variant of the same parent, causes the same acute disease but does not cause CIM. Antimuscle IgG was found in 51% of MP1.23-infected and 58% of MP1.24-infected mice but in just 18% of mice infected with AMP2.17 and in 10% of controls (MP vs AMP: chi(2), P < or =.006). Several staining patterns were observed, indicating that autoantibodies of multiple specificities were produced. Antinuclear antibodies were found in 57% of MP1.23-infected and 27% of MP1.24-infected mice but were rare in mice infected with AMP2.17 (0%) or in controls (4%) (MP vs AMP: chi(2), P < or =.01). Antiviral-antibody titers were higher with MP virus than with AMP virus (ANOVA, P <.001). A trend toward an association between antiviral antibody or autoantibodies and the presence or severity of clinical measures of CIM was noted but was not significant. These data suggest that the autoantibodies do not mediate muscle disease but are an independent manifestation of an immunopathic response induced by infection with MP but not AMP CVB1(T).
Tam
Patricia E
PE
Department of Medicine, University of Minnesota, Minneapolis, 55455, USA. tamxd001@umn.edu
Fontana
Donna R
DR
Messner
Ronald P
RP
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D034961:Antigens, Nuclear / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D002908:Chronic Disease; D003001:Cloning, Molecular; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000473:pathology; D029822:Enterovirus B, Human / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008813:Mice, Inbred ICR; D018482:Muscle, Skeletal / Q000276:immunology* / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D014774:Virulence
D000914:Antibodies, Viral; D034961:Antigens, Nuclear; D001323:Autoantibodies; D007074:Immunoglobulin G