Neuromuscular transmission failure in
myasthenia gravis (MG) is most commonly elicited by
autoantibodies (ab) to the
acetylcholine receptor or the muscle-specific
kinase, constituting AChR-MG and
MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th) 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of
cytokines related to various Th subtypes were determined in patients with AChR-MG,
MuSK-MG and healthy controls (CON). Peripheral blood mononuclear cells (PBMC) were activated in vitro by anti-CD3, and
cytokines were quantified in supernatants. In purified blood CD4+ T cells,
RNA of various
cytokines, Th subtype specific
transcription factors and the co-stimulatory molecule,
CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related
cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from
MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related
cytokines, IFN-γ,
IL-17A and
IL-21. Stimulated expression of
IL-4,
IL-6,
IL-10 and
IL-13 was not significantly different. At the
RNA level, expression of
CD40L by CD4+ T cells was reduced in both AChR-MG and
MuSK-MG patients while expression of Th subset related
cytokines and
transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and
MuSK-MG patients, leaving other
cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of
IL-6 and
IL-10 by cultured PBMC from AChR-MG, but not
MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in
MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and
MuSK-MG, but otherwise modulates immune responses in AChR-MG and
MuSK-MG patients differentially.