Augmented interferon-gamma, interleukin-4 and transforming growth factor-beta mRNA expression in blood mononuclear cells in myasthenia gravis.
The abnormal T lymphocyte-dependent production of antibodies to the nicotinic acetylcholine receptor (AChR) in myasthenia gravis (MG) suggests a role for immunoregulatory cytokines. We examined the T helper type 1 (Th1) cell-associated interferon-gamma (IFN-gamma) that promotes cell-mediated immunity, the Th2 cell-related interleukin-4 (IL-4) that augments B cell immunity, and transforming growth factor-beta (TGF-beta) that downregulates immune responses but enhances isotype switching. Blood mononuclear cells (MNC) expressing cytokine mRNA were enumerated after in situ hybridization with labelled complementary DNA oligonucleotide probes for IFN-gamma, IL-4 and TGF-beta. MG patients had elevated numbers of cells expressing IFN-gamma and IL-4 compared to patients with non-inflammatory neurological diseases and healthy controls, implying that both Th1- and Th2-like cells are involved in MG. TGF-beta-positive cells were also elevated in MG. The levels of cytokine-positive MNC were similar in MG and in control patients with other inflammatory neurological diseases. There were no associations between numbers of cytokine-positive blood MNC and clinical variables of MG, but individual patients need to be studied over the course of MG to clarify a relation between the cytokines under study and clinical or laboratory variables of MG.
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Department of Neurology, Karolinska Institute, Huddinge Hospital, Sweden.
Navikas
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Yu
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Fredrikson
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Osterman
P O
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics*; D015847:Interleukin-4 / Q000032:analysis / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma