The expression of IL-10 on lymphocytes attenuates the response to glucocorticoid therapy in myasthenia gravis patients

Abstract

Myasthenia gravis (MG) is an autoimmune disease in which antibodies bind to acethylcholine receptors or to functionally related molecules in the postsynaptic membrane at the neuromuscular junction. B lymphocytes augment the immune response by producing antibodies and activating T cells by antigen presentation. IL-10 is an immunoregulatory cytokine that plays a pivotal role in controlling excessive inflammation and down-regulating the immune response. IL-10-producing CD19+CD24hiCD38hi regulatory B (Breg) cells are known to attenuate macrophage and dendritic cell activation negatively. Glucocorticoids (GCs) have been widely used as a drug of first choice in MG. The isoform of glucocorticoid receptor (GCR)-alfa is functional when activated by GC. The isoform of GCR-beta act as a dominant-negative inhibitor of GCR and correlates with GC resistance. We studied 61 MG patients and measured the mRNA expression of these GCR isoforms in peripheral blood mononuclear cells by real time RT-PCR assay. The frequency of IL-10+CD24+CD38+ Bregs in CD19+ B cells and the expression of IL-10 on CD4+ T cells or CD19+ B cells were detected by flowcytometry. The expression of IL-10 on CD4+T cells in the MG patients were lower than those in healthy subjects (p=0.007). Compare to the healthy subjects, both the mRNA expression of GCR-alfa and GCR-beta were also lower in the MG patients (p=0.002 and p=0.03, respectively). There was a significant negative correlation between the GCR-alfa mRNA expression on lymphocytes and the IL-10 in CD4+ T cells (p=0.006). We divided these MG patients according to the MGFA clinical classification and compared the percentage of IL-10+CD24+CD38+ cells in CD19+B cells among the groups. The percentage of IL-10+CD24+CD38+cells in CD19+B cells in the class 0 group (no symptom) were significantly higher than those in the class I group or class II group (p=0.0001 or p=0.0003, respectively). There was a significant negative correlation between the changing rate of anti ACh-R antibody titer and the percentage of IL-10+cells in CD19+B cells (p=0.014). These data suggest that IL-10 production from lymphocytes may affect the clinical response to GC treatment in MG patients.