PROGNOSTIC MARKERS IN PATIENTS WITH THYMUS-INDEPENDENT AND THYMUS-DEPENDENT MYASTHENIA GRAVIS

Abstract

Objective. To assess the presence of specific markers in patients with thymus-independent and thymus-dependent myasthenia gravis for choosing treatment tactics. Methods. The presence of specific markers was assessed in 138 patients with thymus-independent (M - myasthenia gravis without thymus changes) and thymus-dependent (MH - myasthenia gravis with thymus hyperplasia, MT - myasthenia gravis with thymoma). The method ELISA (the content of antibodies to subunits 1 and 7 nAChR in blood serum, to 7 nAChR subunit in thymocyte mitochondria, a detectablelevel of antinuclear antibody(ANA), immunofluorescence (ANA glow) and flow cytometry (expression of CD14+CD11c+and CD14 + HLA-DR +) has been used. Results. The relationship between the clinical phenotypes of myasthenia gravis and the variants of HLA diplotypes was revealed: in young patients with thymus-independent myasthenia gravis (M), a high heterogeneity of the genotypic markers HLA-DR (DR1, DR2, DR3, DR5, DR7) was detected. Patients with thymus-dependent myasthenia (MT) had only the HLA DR2 and HLA DR7 diplo- and haplotypes. The presence of HLA DR2 and HLA DR7 haplotypes in some young patients with progressive thymus-independent myasthenia gravis (M) led to the development of myasthenia gravis with thymoma (MT) in the elderly people. The pathogenic role also belongs to infection (СMV, EBV, HBV, HCV, HSV-1, HSV-2, HHV-6, mycoplasma) and food intolerance (IgE and IgG4) in the development and progression of myasthenia gravis. A four-fold prevalence of α7 subunit nicotinic acetylcholine receptors on the thymocyte mitochondria as an additional targets of autoimmune aggression in myasthenia gravis was determined. Specific antinuclear antibodies to centromere chromosome proteins were visualized in the elderly people with thymoma. Conclusion. The prognosis of the myasthenia gravis progression and the development of remission can be made using genomic (the presence of certain HLA-DR haplotypes) and molecular (ANA antibodies to centromere chromosome proteins, expression of CD20+, CD14+CD11c+, CD14+HLA-DR+) biomarkers, that can be used for the choice of treatment tactics. What this paper adds The change of complex biomarkers has been firstly studied for prognosis and choice of complex treatment tactics for young patients with progressive thymus-independent myasthenia gravis and for the elderly patients with thymus-dependent myasthenia gravis. In the presence of certain HLA-DR haplotypes, antinuclear antibodies to centromere chromosome proteins, an increasing expression of CD20+, CD14+CD11c+ and CD14+HLADR+ in some young patients with thymus-independent myasthenia gravis, analogically to biomarkers in thymus-dependent myasthenia gravis with thymoma, to perform a thymectomy is of high dangerous. potentialrisksof the procedure.