Induction of multiple heart autoantibodies in mice with coxsackievirus B3- and cardiac myosin-induced autoimmune myocarditis.
When mice of certain strains are infected with the cardiotropic virus coxsackievirus B3 or are immunized with mouse cardiac myosin, myocarditis, accompanied by immune recognition of the myocardium, ensues. That both target organ injury and peripheral immunization lead to similar disease manifestations raise questions about the role of tissue damage in eliciting autoantibodies. A/J mice were infected with coxsackievirus B3 or immunized with mouse cardiac myosin and killed at weekly intervals for 4 wk. A portion of each heart was examined histologically for evidence of myocarditis and antibodies were eluted from the remaining heart tissue. Heart eluates and serum were tested for IgG antibodies to myosin and to adenine nucleotide translocator and branched chain ketoacid dehydrogenase molecules by ELISA. At each sampling time, coxsackievirus B3-infected mice exhibited high titers of circulating antibodies to myosin, adenine nucleotide translocator, and branched chain ketoacid dehydrogenase with successively increasing myocardial deposition of antibodies of each specificity. Among myosin-immunized mice, antibodies of all three specificities were eluted from the myocardium and were found in the serum, but only antibodies to myosin were present in appreciable amounts in the circulation. Antibodies to myosin, adenine nucleotide translocator, and branched chain ketoacid dehydrogenase were rarely observed in serum and heart eluates from control animals. This study indicates that myocardial injury may be a prerequisite for the induction of cardiac autoimmunity and suggests that as tissue damage accrues, recognition of additional cardiac Ag may occur.
Neumann
D A
DA
Johns Hopkins University, School of Hygiene and Public Health, Department of Immunology and Infectious Diseases, Baltimore, MD 21205.
Rose
N R
NR
Ansari
A A
AA
Herskowitz
A
A
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D003384:Coxsackievirus Infections / Q000276:immunology; D029822:Enterovirus B, Human; D007658:Ketone Oxidoreductases / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D000226:Mitochondrial ADP, ATP Translocases / Q000276:immunology; D009097:Multienzyme Complexes / Q000276:immunology; D009205:Myocarditis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D009218:Myosins / Q000276:immunology
D001323:Autoantibodies; D009097:Multienzyme Complexes; D000226:Mitochondrial ADP, ATP Translocases; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D009218:Myosins