Altered expression of chemokine receptor CXCR5 on T cells of myasthenia gravis patients

Myasthenia gravis (MG) is characterized by the T cell-dependent production of anti-acetylcholine receptor (AChR) antibodies. The chemokine receptor CXCR5 regulates lymphocyte migration and is expressed on a subset of CD4⁺ T cells named follicular helper T cells (T_FH), the key modulators of antibody production by B cells. We studied the frequency of CXCR5-positive lymphocytes in the peripheral blood of MG patients before and after therapy (thymectomy plus glucocorticoid). Before therapy, the MG patients showed a significantly higher frequency of CXCR5⁺ CD4⁺ T cells in the peripheral blood compared with the control group, while no significant difference in the percentages of CXCR5⁺ CD4⁺ T cells was observed between the patients of the hyperplasia group and those of the thymoma group. The CXCR5⁺ CD4⁺ T cell frequency correlated with the disease severity. The CXCR5⁺ CD4⁺ T cell frequency of MG patients positive for other autoantibodies together with anti-AChR antibodies was significantly higher than in those having only anti-AChR antibodies. After therapy, the CXCR5⁺ CD4⁺ T cell percentage decreased gradually to the control level with a significant inverse correlation between the CXCR5⁺ CD4⁺ T cell frequency and duration after the initiation of MG therapy. The CXCR5⁺ CD4⁺ T cell populations in the hyperplastic thymuses and thymomas were not significantly different from those in the control thymuses. These results suggest that CXCR5⁺ CD4⁺ T cells play an important role in the disease activity of MG and that some MG patients have a systemic abnormality in T cell-dependent antibody production.