Investi̇gation of the expression profi̇les of trail ligand and receptors and the antiapoptotic nfkb molecule activation in thymic tissues of patients wi̇th myasthenia gravis

Myasthenia Gravis (MG) is a heterogeneous autoimmune neuromuscular disease, accompanied by different thymic abnormalities. Approximately 40-70% of the MG patients display follicular tymic hyperplasia, while 10-15% of the cases have thymoma. TNF-Related Apoptosis-Inducing Ligand (TRAIL) is one of the many TNF family members investigated for a possible role in the negative selection of thymocytes in thymus. Related studies point out for a regulator role of TRAIL throughout this process. Yet the results are controversial, and the putative role of TRAIL in development of MG is yet to be clarified. It is well known that alterations in the expression levels of TRAIL ligand and its receptors is significant, in terms of different roles exerted by TRAIL in different tissues and at different times in progression of various diseases. Thus, we investigated the expression levels of TRAIL ligand and receptors in 22 MG patients with thymoma, 5 MG patients with thymic hyperplasia, and in 10 normal thymic tissue samples. Furthermore, activation levels of the antiapoptotic NFkB molecule, which can inhibit the apoptotic effects of TRAIL were examined. In addition, the apoptotic cell counts in all three types of tissues were detected, and their correlations with TRAIL expression levels were investigated. Our results revealed that expression levels of DR4, DR5, and DcR2 receptors were significantly higher in thymoma, while thymic hyperplasia displayed an increased level of DR5 expression. On the other hand, there was no statistically significant difference between the expression levels of TRAIL in thymoma, thymic hyperplasia, or normal thymic tissues. Furthermore, analysis targeting active forms of NFkB revealed no active NFkB levels in abnormal or normal thymic tissues. Our results were evaluated in terms of TRAIL's putative role in normal thymus and thymic anomalies, and in terms of applicability of a possible TRAIL-mediated thymectomy. Key Words: TRAIL, Myasthenia Gravis, NFkB, Thymus, Thymic Hyperplasia, Thymoma