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Abstract
The purpose of the study: was to compare the level of antibodies to double-stranded (native) DNA (AТ dsDNA), the prevalence of AA and AG haplotypes, the nature of the prognosis, and the degree of disability according to the EDSS scale in patients with sporadic and familial forms of multiple sclerosis and practically healthy children with a burdened heredity to this disease.
Research methods: clinical and neurological, genetic, methods of mathematical statistics (mean values, confidence interval, permutation test, ANOVA, Pearson correlation analysis, standard correlation tables).
Ninety-seven patients were examined: sporadic form of multiple sclerosis (MS) — 55, including those with relapsing-remitting (RR) — 31, progressive types of the course (PTC) — 24; familial form of MS — 42, including 20 with relapsing-remitting and 22 with progressive types of course), practically healthy adult children (18 to 36 years old) with a burdened heredity for MS — 22.
In patients with MS, the ratio of normal and elevated AT dsDNA titres, regardless of the form of the disease (sporadic, familial), is closely related to the types of the disease with a predominance of normal titres in RR and elevated titres in PTC. When comparing the mean values of AT dsDNA titres, a significant prevalence of elevated titres in patients with MS, especially in the familial form, was found compared to the group of practically healthy children. The dependence of the average values of AT dsDNA titres on the nature of the prognosis was obtained: the lowest value of the average titres in favourable prognosis, the highest — in unfavourable prognosis. When assessing the severity of neurological deficit, according to the EDSS disability scale, there was no correlation between the level of AT dsDNA and the prevalence of AA and AG haplotypes in two forms of MS.
The prevalence of AA and AG haplotypes does not depend on the form of MS (sporadic, familial), but is closely related to the type of course with a significant prevalence of the AG haplotype in patients with PTP MS. In practically healthy children, the prevalence of the AA haplotype prevailed over the AG haplotype (p > 0,05). When analysing the mean prevalence of AA and AG haplotypes in patients with two forms of MS, a significant predominance of the AG haplotype was found, in contrast to the group of healthy children, in whom the ratio of haplotype prevalence changed in favour of the AA haplotype. When using the linkage tables, there were no significant differences between the prevalence of AA and AG haplotypes, the nature of the prognosis and the severity of neurological deficit (according to the EDSS scale) in the two forms of MS. According to the mean values in the analysis of the relationship between the content of AT dsDNA content and the prevalence of AA and AG haplotypes, it was proved that more active production of antibodies to DNA is predominantly initiated by the AG haplotype in the two forms of MS.
Thus, a comprehensive mathematical analysis of clinical genetic studies made it possible to assess the complexity of the relationship between the ratio of normal and elevated AТ dsDNA titres, the prevalence and distribution of AA and AG haplotypes, the severity of neurological deficits (according to the EDSS disability scale), and the nature of the prognosis in sporadic and familial forms of MS. These studies are of theoretical and practical interest and are the basis for further clarification of the pathogenetic mechanisms of the demyelinating process and improvement of diagnosis and prognosis in various forms and types of MS.
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The Scientific and Practical Journal of Medicine
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