GENOMIC AND EPIGENOMIC PREDICTORS FOR VARIOUS CLINICAL PHENOTYPES OF MYASTHENIA GRAVIS

The aim: To evaluate the relationship of certain alleles of HLA class II leukocyte antigens and the profile of antibodies to various subunits of nicotinic acetylcholine receptors (nAChR), the level of Treg lymphocytes and the serum concentration of anti-inflammatory IL-10 for various clinical myasthenia gravis phenotypes.

Materials and methods: We examined 217 patients with thymus-independent myasthenia (n = 42) and thymus-dependent myasthenia, among them patients with thymus hyperplasia (n = 108) and thymoma (n = 67). We used the following methods: ELISA, flow cytometry, light and fluorescence microscopy.

Results: Certain genomic (polymorphism of leukocyte HLA-DR antigens) and epigenomic (antibodies to α1 and α7 nAChR subunits, expression of Treg lymphocytes and concentration of cytokines) predictors were identified for various myasthenia phenotypes. The presence of HLA haplotypes DR2 and DR7 in some young patients with M with disease progression led to the development of myasthenia gravis with thymoma (MT) at an older age. The presence of α7 nAChR subunit on thymocyte mitochondria was revealed, which is an additional autoimmune target for autoantibodies in patients with myasthenia gravis. An increase in the concentration of cytokines (IL-4, IL-8, IFN-γ) in all patients with myasthenia gravis was revealed.

Conclusions: Estimate the features of the formation of various variants of the immune response in thymus-independent and thymus-dependent myasthenia gravis is a necessary condition for targeted immunocorrection or surgery.