IL-12 is involved in the induction of experimental autoimmune myasthenia gravis, an antibody-mediated disease

Lucia Moiola, Francesca Galbiati, Gianvito Martino, Stefano Amadio, Elena Brambilla, Giancarlo Comi, Angela Vincent, Luigi M E Grimaldi, Luciano Adorini

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Abstract

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-γ 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 1L-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.

Original languageEnglish
Pages (from-to)2487-2497
Number of pages11
JournalEuropean Journal of Immunology
Volume28
Issue number8
DOIs
Publication statusPublished - Aug 1998

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Keywords

  • Experimental autoimmune myasthenia gravis
  • IgG2a
  • IL-12
  • Muscle nicotinic acetylcholine receptor
  • Th1

ASJC Scopus subject areas

  • Immunology

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