Endogenic Cytotoxic Factors and Formation of the Clinic Forms of Myasthenia

Background: Recently, increased incidence of autoimmune disorders, one of which is myasthenia gravis. The myasthenia is revealed at 3-30 patients out of 100 000 in a year. As it is considered by the most of specialists the central chain in myasthenia development is the formation of antibodies to the nicotinic acetylcholine receptors (nAChR), leading to the blockage of muscle fiber contraction and to the muscle dystrophy. Along with this, there is an assumption of the role of cytotoxic factors in the development of myasthenia gravis. The aim of the present article is to proof working hypothesis about specific role of cytotoxic factors in the formation of various clinical variants of myasthenia gravis. Method: Patients were divided according to the clinical phenotype of myasthenia gravis: myasthenia without thymus lesion (M), myasthenia with thymus hyperplasia (MH) and myasthenia with thymoma (MT). We used methods of light microscopy to determine the serum cytotoxicity using a cell bioindicator Dunaliella viridis. The determination of antibodies to nicotinic acetylcholine receptors (nAChR), thyroperoxidase (TPO) and antibodies to lungs, liver tissues and elastin was performed by ELISA. And fluorescence microscopy used for determination of expression of clusters differentiation of CD3+, CD4+, CD8+, CD16+, CD19+, CD45+. Results: The patients with different clinical phenotypes of myasthenia: myasthenia without thymus lesions (M), myasthenia with thymus hyperplasia (MH), and myasthenia with thymoma (MT), have been investigated. It was discovered that the amount of autoantibodies to the α1 and α7 acetylcholine receptor was different among patients with different clinical types of myasthenia. Drastic differences between forms of myasthenia were also identified using a blood serum thyroperoxidase activity. Additionally, we found that all clinical forms of myasthenia could be characterized by the differences in the amounts of IL4 and IL8, compositions of lymphocyte subpopulations, as well as patterns of autoantibodies to the lung tissue, liver, heart, and DNA. Test culture D. viridis responded differently to the cytotoxic components of the blood serum in different clinical types of myasthenia. Our results suggest that endogenous factors play a primary role in forming of clinical types of myasthenia. Conclusions: 1) development of myasthenia gravis occurs on the background of cytotoxic factors formed in the organism; 2) endogenous cytotoxic factors have nonspecific effects on the various functional systems of the organism, even the plant objects; 3) the organism of patients with myasthenia gravis produce various cytotoxic factors, which influence on different systems of the organism and can lead to the formation of a variety of clinical phenotypes.