ABSTRACT
Although myasthenia gravis (MG) is a classic autoantibody-mediated disease, T cells are centrally involved in its pathogenesis. In recent years a number of studies have analyzed the role of CD4+ FoxP3+ regulatory T cells (Treg) in the disease with contradictory results. Here, the generation of Treg was significantly reduced in thymoma as compared to thymic hyperplasia and normal thymus tissue (p=0.0002). In the peripheral blood, Treg subsets classified according to CD49d, HELIOS and CD45RA expression changed after thymectomy and in the long-term course of immunosuppression. Compared to healthy volunteers the frequency of CD45RA+FoxP3low Treg was reduced in MG patients in general (p=0.037) and in particular in patients without immunosuppression (p=0.036). In our study, thymectomy and immunosuppressive treatment were associated with changes in Treg subpopulations. The reduced frequency of CD45RA+FoxP3low Treg we observed in MG patients might play a role in MG pathogenesis.
Subject(s)
Myasthenia Gravis/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Myasthenia Gravis/drug therapy , Myasthenia Gravis/surgery , T-Lymphocyte Subsets/drug effects , T-Lymphocytes, Regulatory/drug effects , Thymectomy , Thymoma/drug therapy , Thymoma/immunology , Thymoma/surgery , Thymus Gland/pathology , Thymus Hyperplasia/drug therapy , Thymus Hyperplasia/immunology , Thymus Hyperplasia/surgery , Thymus Neoplasms/drug therapy , Thymus Neoplasms/immunology , Thymus Neoplasms/surgeryABSTRACT
Whether there is a general perturbation of B and plasma cell subsets in myasthenia gravis (MG) has not been investigated so far. Here we performed a detailed flow cytometric analysis of blood and if available thymic tissue in order to detect MG-specific and therapy-induced changes. We observed significant differences in the distribution of B cell subsets in MG patients, yet these were mainly attributable to medical treatment. Furthermore MG is associated with significantly increased frequencies of plasma cells that were especially activated in purely ocular disease manifestation. In contrast to thymoma, B cell subset distribution in hyperplastic thymus could be distinguished from peripheral blood, however both tissues were not significantly enriched with plasma cells. Thus B cell differentiation in general is not defective in MG, but modified by therapy and enhanced frequencies of plasma cells can be detected in MG patients.
