Exacerbated pathology of viral encephalitis in mice with central nervous system-specific autoantibodies.
We examine here the outcome of viral encephalomyelitis [mouse hepatitis virus (MHV) A59, Theiler's encephalomyelitis virus, and Coxsackievirus B3] in mice with autoantibodies to a central nervous system (CNS)-specific antigen, myelin oligodendrocyte glycoprotein, that usually develop no clinical disease. Morbidity and mortality of the acute viral CNS disease was augmented by the presence of the autoantibodies in all three viral infections. Transfer of serum containing the autoantibodies at the time of infection with MHV was sufficient to reproduce the exacerbated disease. The presence of the autoantibodies was found to result in increased infiltration of mononuclear cells into the brain. Early demyelination was severely augmented in brains and spinal cords of MHV-infected mice with CNS-specific autoantibodies. The antibody-mediated exacerbation was shown to be independent of the complement system but to require expression of Fc receptors, because it was observed in C'-3-deficient but not in Fc receptor-deficient mice. Our study illustrates the possibility that infections can lead to much more profound immunopathology in the presence of an otherwise latent autoimmune condition.
Burrer
Renaud
R
Molecular and Integrative Neurosciences Department, The Scrips Research Institute, La Jolla, CA 92037, USA.
Buchmeier
Michael J
MJ
Wolfe
Tom
T
Ting
Joey P C
JP
Feuer
Ralph
R
Iglesias
Antonio
A
von Herrath
Matthias G
MG
D000208:Acute Disease; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000821:virology; D003176:Complement C3 / Q000172:deficiency / Q000276:immunology; D018792:Encephalitis, Viral / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D011961:Receptors, Fc / Q000172:deficiency / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology / Q000821:virology; D019076:Transgenes / Q000276:immunology
D003176:Complement C3; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011961:Receptors, Fc