IL-12 is involved in the induction of experimental autoimmune myasthenia gravis, an antibody-mediated disease.
IL-12 has been shown to be involved in the pathogenesis of Th1-mediated autoimmune diseases, but its role in antibody-mediated autoimmune pathologies is still unclear. We investigated the effects of exogenous and endogenous IL-12 in experimental autoimmune myasthenia gravis (EAMG). EAMG is an animal model for myasthenia gravis, a T cell-dependent, autoantibody-mediated disorder of neuromuscular transmission caused by antibodies to the muscle nicotinic acetylcholine receptor (AChR). Administration of IL-12 with Torpedo AChR (ToAChR) to C57BL/6 (B6) mice resulted in increased ToAChR-specific IFN-gamma production and increased anti-ToAChR IgG2a serum antibodies compared with B6 mice primed with ToAChR alone. These changes were associated with earlier and greater neurophysiological evidence of EAMG in the IL-12-treated mice, and reduced numbers of AChR. By contrast, when IL-12-deficient mice were immunized with ToAChR, ToAChR-specific Th1 cells and anti-ToAChR IgG2a serum antibodies were reduced compared to ToAChR-primed normal B6 mice, and the IL-12-deficient mice showed almost no neurophysiological evidence of EAMG and less reduction in AChR. These results indicate an important role of IL-12 in the induction of an antibody-mediated autoimmune disease, suggest that Th1-dependent complement-fixing IgG2a anti-AChR antibodies are involved in the pathogenesis of EAMG, and help to account for the lack of correlation between anti-AChR levels and clinical disease seen in many earlier studies.
Department of Biotechnology, San Raffaele Hospital, San Raffaele Scientific Institute, Milan, Italy.
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L
Moiola
F
F
Galbiati
G
G
Martino
S
S
Amadio
E
E
Brambilla
G
G
Comi
A
A
Vincent
L M
LM
Grimaldi
L
L
Adorini
D000818:Animals; D004195:Disease Models, Animal; D004576:Electromyography; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage / Q000172:deficiency / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009157:Myasthenia Gravis / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000503:physiopathology; D011950:Receptors, Cholinergic / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014101:Torpedo
D007074:Immunoglobulin G; D011950:Receptors, Cholinergic; D018664:Interleukin-12; D007371:Interferon-gamma