Influence Of Immunosuppressive Medication on TCR Vβ Usage And Thymocyte Maturation Stages In Patients With Early-Onset Myasthenia Gravis (P2.095)

OBJECTIVE: To investigate the influence of immunosuppressive medication on TCR Vβ usage and thymocyte maturation stages in patients with early-onset myasthenia gravis (MG). BACKGROUND: It is not clear whether mechanisms of central or peripheral tolerance are disturbed in early-onset MG. Nor is it known which influence immunosuppressive medication has got on these mechanisms. DESIGN/METHODS: Thymus and blood lymphocytes from 40 patients with early-onset MG and 21 immunological healthy probands were examined by fluorescence activated cell sorting. The MG patients were stratified into two subgroups: the ones who had not been treated immunosuppressively at the time of thymectomy and those who had taken corticosteroids or azathioprine at that time. RESULTS: TCR Vβ chain analysis showed no significant differences in the thymus. In the blood a significant higher number of Vβ expansions was found on CD4+ positive lymphocytes in both MG subgroups when compared with the normal controls. The two MG subgroups did not differ significantly. The comparison of the thymus compartment with the blood yielded a significant elevated number of Vβ expansions in the blood in both MG subgroups. Investigation of thymocyte maturation stages showed an increased appearance of the late double positive and the early CD4+ single positive stages in immunosuppressive naive MG patients when compared with normal controls and a decreased appearance of the mentioned stages in the immunosuppressively treated MG subgroup compared with the untreated MG subgroup. CONCLUSIONS: The results argue for a disturbation of peripheral tolerance in patients with autoimmune early-onset MG, on which immunosuppressive medication has got no influence. There also is evidence for a disturbation of central tolerance in autoimmune early-onset MG and an influence of corticosteroids or azathioprine that supports negative selection in the thymus. Disclosure: Dr Eienbroker has received personal compensation for activities with Biogen Idec, Novartis, and Temmler Pharma. Dr. Putz has nothing to disclose. Dr. Schlegel has nothing to disclose. Dr. Gellert has nothing to disclose. Dr. Sommer has nothing to disclose. Dr. Seitz has nothing to disclose. Dr. Oertel has received personal compensation for activities with Boehringer Ingelheim Pharmaceuticals Inc., Cephalon, Merck & Co. Inc., Merck Sharp & Dohme Ltd., Merck Serono, Mundipharma, Novartis, Schwarz Pharma, Neuroscience /UCB Pharma, Pfizer Inc., Synovia, Teva Neuroscience, and Desitin. Dr. Oertel holds stock and/or stock options in Roche Diagnostics Corp. which sponsored research in which Dr. Oertel was involved as an investigator. Dr. Oertel has received research support from UCB Pharma, Teva Neuroscience, International Parkinson Foundation, and the Michael J Fox Foundation. Dr. Tackenberg has received personal compensation for activities with Bayer Pharmaceuticals Corp., Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. Dr. Tackenberg has received research support from Bayer Pharmaceuticals Corp., Biogen Idec, and Novartis.