Autoantibodies to IL-12 in myasthenia gravis patients with thymoma; effects on the IFN-gamma responses of healthy CD4+ T cells

J Neuroimmunol. 2003 Jun;139(1-2):102-8. doi: 10.1016/s0165-5728(03)00136-x.

Abstract

In humans, interleukin-12 (IL-12) and interferon-alpha (IFN-alpha) normally favor IFN-gamma-producing "Th1" T cell responses. Myasthenia gravis (MG) patients with thymomas frequently have high-titer neutralizing autoantibodies against these cytokines, but not against IFN-gamma. Because they occasionally develop intractable (even fatal) infections, we have tested effects of their sera on the generation of IFN-gamma responses by healthy adult T cells to autologous lipopolysaccharide (LPS)-treated dendritic cells (DC). Anti-IL-12(+) sera consistently reduced IFN-gamma responses substantially, whether assessed by intracellular staining or ELISA. Therefore, thymoma patients with intractable infections might benefit from cautious IFN-gamma therapy. We discuss wider implications of the surprising rarity of clear clinical hazards-or benefits-of these autoantibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Autoantibodies / pharmacology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Communication / drug effects
  • Cell Communication / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology
  • Immunoglobulin G / pharmacology
  • Interferon-alpha / blood
  • Interferon-alpha / immunology
  • Interferon-gamma / immunology*
  • Interferon-gamma / metabolism
  • Interferon-gamma / therapeutic use
  • Interleukin-12 / blood
  • Interleukin-12 / immunology*
  • Interleukin-4 / blood
  • Lipopolysaccharides / pharmacology
  • Male
  • Middle Aged
  • Myasthenia Gravis / blood
  • Myasthenia Gravis / complications*
  • Myasthenia Gravis / immunology*
  • Thymoma / blood
  • Thymoma / complications*
  • Thymoma / immunology*

Substances

  • Autoantibodies
  • Immunoglobulin G
  • Interferon-alpha
  • Lipopolysaccharides
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma