Increased levels of circulating acetylcholine receptor (AChR)-reactive IL-10-secreting cells are characteristic for myasthenia gravis (MG)

Abstract

SUMMARY Antibodies to the nicotinic AChR are pivotal in the immunopathogenesis of MG. Cytokines produced by T-helper cells are important regulators of humoral immune responses. IL-10 is considered an anti-inflammatory cytokine, but it promotes B cell activation and worsens experimental autoimmune MG in Lewis rats, an experimental model of MG. To study IL-10 and, as a control, interferon-gamma (IFN-γ) in MG, we used an enzyme-linked immunospot (ELISPOT) assay, thereby assessing numbers of blood mononuclear cells (MNC) secreting IL-10 and IFN-γ spontaneously and after stimulation with AChR. Low numbers of IL-10-secreting cells were regularly found in peripheral blood from patients with MG as well as in controls with other neurological diseases and healthy subjects. However, only MG patients had elevated blood levels of AChR-reactive IL-10- and IFN-γ-secreting cells. The MG patients showed no responses to the control autoantigen myelin basic protein, underlining the specificity of the IL-10 and IFN-γ responses. Immunosuppressive treatment reduced numbers of AChR-reactive IFN-γ-secreting cells but increased the numbers of IL-10-secreting cells. The numbers of IL-10-secreting cells tended to be higher in patients with generalized versus ocular MG, further suggesting that the augmented IL-10 responses may be important in the pathogenesis and perpetuation of MG.