title: Autoantibodies to IL-12 in myasthenia gravis patients with thymoma; effects on the IFN-gamma responses of healthy CD4+ T cells.
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.
authors.affiliation: Neuroscience Group, Weatherall Institute for Molecular Medicine, University of Oxford, OX3 9DS, Oxford, UK.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: J-L
authors.initials: JL
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Meager
authors.forename: J
authors.initials: J
authors.lastname: Newsom-Davis
authors.forename: N
authors.initials: N
authors.lastname: Willcox
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007074:Immunoglobulin G / Q000494:pharmacology; D016898:Interferon-alpha / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D018664:Interleukin-12 / Q000097:blood / Q000276:immunology*; D015847:Interleukin-4 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood / Q000150:complications* / Q000276:immunology*; D013945:Thymoma / Q000097:blood / Q000150:complications* / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma