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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Autoantibodies / blood
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Autoantibodies / immunology*
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Autoantibodies / pharmacology
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Cell Communication / drug effects
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Cell Communication / immunology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Female
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Humans
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Immunity, Cellular / drug effects
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Immunity, Cellular / immunology
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Immunoglobulin G / pharmacology
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Interferon-alpha / blood
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Interferon-alpha / immunology
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Interferon-gamma / immunology*
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Interferon-gamma / metabolism
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Interferon-gamma / therapeutic use
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Interleukin-12 / blood
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Interleukin-12 / immunology*
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Interleukin-4 / blood
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Lipopolysaccharides / pharmacology
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Male
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Middle Aged
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Myasthenia Gravis / blood
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Myasthenia Gravis / complications*
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Myasthenia Gravis / immunology*
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Thymoma / blood
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Thymoma / complications*
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Thymoma / immunology*
Substances
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Autoantibodies
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Immunoglobulin G
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Interferon-alpha
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Lipopolysaccharides
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Interleukin-12
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Interleukin-4
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Interferon-gamma