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Inheritance in patients with multiple sclerosis
16. Taba P., Asser T. Incidence of Parkinson's disease in estonia//Neuroepidemiology. - 2003. - Vol. 22, № 1. - P. 41-45.
17. Vines J. J., Larumbe R., Gaminde I., Artazcoz M. T. Incidence of idiopathic and secondary Parkinson disease in Navarre. Population-based case registry//Neurologia. - 1999. - Vol. 14, № 1. - P. 16-22.
18. Yamawaki M., Kusumi M., Kowa H., Nakashima K. Changes in prevalence and incidence of Parkinson's disease in Japan during a quarter of a century//Neuroepidemiology. - 2009. - Vol. 32. - P. 263-269.
19. Международная статистическая классификация болезней и проблем, связанных со здоровьем; 10-й пересмотр: в 3 т./ВОЗ. -Женева, 1995-1998. - Т. 1-3.
20. Пресс-релиз ВОЗ. 1998//[Electronic resource]. - Available from: http://www.who.int/inf- pr-1998/en/pr98-71.html
21. Карданова К. А. Актуальные вопросы в изучении паркинсонизма с точки зрения медицинской статистики//Международный студенческий научный вестник. - 2015. - № 2-1. - С. 100//[Electronic resource]. - Available from: http://www.eduherald.ru/ru/ar-ticle/view?id=12197.
22. Обновления ВОЗ 1996-2014 rr.//[Electronic resource]. - Available from: http://www.who.int/classifications/icd10updates/en/in-dex.html
Muhadzhieva Liana Alievna, Kudrya Viktoria Sergeevna, Ibragimov Magomed Magomedovich, Karpov Sergey Michailovich, Vyshlova Irina Andreevna, Stavropol State Medical University, Russia, Department of neurology, neurosurgery and medical genetics
E-mail: [email protected]
Inheritance in patients with multiple sclerosis
Abstract: The problem of heredity of multiple sclerosis (MS) is an important practical issue, as the etiology and pathogenesis of this disease isn't well understood. The urgency of this problem stems from the fact that the number of multiple sclerosis patients is increasing every year, with the proportion of women among the infected is 52 %, while the share of men is 48 % [1; 2].
Keywords: multiple sclerosis, inheritance.
The incidence of multiple sclerosis most highly prevalent among the white population of the globe, especially in areas inhabited by immigrants from Northern and Central Europe as well as Scandinavia. The number of patients among the small ethnic groups of the population, are still not considered to be involved in the disease. Among the Slavic population in the republics of the Caucasus and Central Asia, the prevalence of MS was much less than in the European part of Russia [6]. Objective
To analyze the genetic predisposition to multiple sclerosis. Results
Multiple sclerosis — a chronic, progressive disease that affects the brain and spinal cord, that result in violations of muscle control, blurred vision, disturbance of body balance, sensory disturbances [8].
Multiple Sclerosis is not a hereditary disease, but observations indicate the presence of certain hereditary (genetic) predisposition [1; 2; 3]. These assumptions are based on the results of epidemiological studies that multiple sclerosis affects mainly people with white skin, as evidenced not only data on the prevalence of the disease in terms of its geographical distribution, but also the difference in the incidence rate between the white and black population countries in the Americas and South Africa [1].
It is assumed that a predisposition to the disease multiple sclerosis is caused by the presence of several genes (polygenic inheritance). It is also possible genetic polymorphism [4]. This is indicated by twin data and genealogical research, as well as non-linear reduction in the risk of the disease among relatives of the patient
with a decrease in the degree of kinship. For siblings of the patient the probability of the disease in their lifetime is 2-5 %, while it is slightly lower [5] for parents and children.
Genetic susceptibility to multiple sclerosis, presumably associated with a given individual a combination of several genes that determine disorders, especially in immunoregulation system.
The data obtained from the analysis of different populations suggests that patients with multiple sclerosis significantly increased frequency of antigen HLA-A3, HLA-B7, HLA-DR2, HLA-DR3, HLA-DQ6 and other [1; 3]. In multiple sclerosis, also noted the association of the disease with certain haplotypes of HLA, including specific combinations of loci allelic MHC.
In multiple sclerosis, there is damage to the nervous system's own immune system cells. These cells enter the brain, destroy the myelin sheath of nerve fibers and lead to scarring. This nervous tissue are replaced by connective [8].
Multiple sclerosis is the most difficult demielinizirute disease of the Central nervous system with predominant autoimmune mechanism of development, remitting disseminated over, affecting people of young age and inevitably resulting in disability. Over the last three decades of domestic and foreign scientists (Schmidt E., Khondkarian A. O., Leonovich A. L., Gusev E. I., Boiko A. N., Zavalishin I. A., Demina T. L., Jerusalem A. P, Pohorski A. M., Shevchenko P. P., Stolyarov I. D, Poser C. M., McDpnald W. I., Ebers G. C., Lauer K., Sadovnick A. D. and others) enormous work has been done on the standardization and systematization of methods of epidemiological analysis in multiple sclerosis, which contributed to the accumulation of the volume of objective
Section 6. Medical science
information, which allows to judge the more authentic distribution of multiple sclerosis in the world [6].
The pathogenesis of multiple sclerosis consists of a complex im-munopathological and pathochemical reactions developing in the nervous system. It is believed that immune processes are induced antigenic structures of the CNS and especially — the main protein of the myelin glycoprotein and myelin — oligodendrocyte macromol-ecules. Energichnyh activation of T-lymphocytes in the periphery (outside the CNS) is the first stage of the immunopathogenesis of multiple sclerosis. Note that autoreactive clones of T-lymphocytes that react with self antigens of the CNS, are present in healthy people, but in minimum quantities and in an inactive state.
Immunological changes in multiple sclerosis are manifested by abnormalities of cellular and humoral immunity. Of cellular reactivity are determined by: the decrease in the content of T-suppressor cells, suppression of T-cell response to mitogens, low potential of NK-cells and altered production of interferon, the increased cytotoxicity of mononuclear cells, changes in the system of interleukins.
The activity of immunopathological reactions is determined by the level of antigen-presentation in the tissue and activity of cell adhesion to the vascular endothelium, activation of T-cells, which in response to some antigens may have a polyclonal nature. The balance of suppressor and activation of cytokines, their soluble receptors and inhibitors is crucial in the progression of immunopathological process in the CNS.
Emerging in scattered sklerose in white matter ofbrain and spinal cord the pathological lesions are called plaques. The leading feature of these lesions is demyelination. Activation of resident cells of the CNS — microglia and astroglia — stimulates the secretion of their cytokines and chemokines (factors that attract cells to the area of inflammation). In the pockets of migrating cells ofhematogenous origin monocytes/macrophages, T- and b-lymphocytes. So begins the formation ofplaque. In inflammation cells secrete a variety of active molecules: cytokines, antibodies, oxygen and nitrogen radicals, proteases. These molecules are the main factors of damage to oligodendrocytes and myelin. The ongoing destruction of myelin leads to the appearance in it proteoliticeski active fragments, which contributes to its further damage. The fibers in the inflammation demyelinated fibers and disturbed the nerve impulse, which leads to the appearance of
clinical symptoms. Simultaneously with the process is demyelination and remyelination, which is especially noticeable at the edges of active plaques. However, despite the emergence of the process of remyelination at the early stages ofplaque formation, restoration of the myelin sheath occurs efficiently enough. The longer the disease, the less pronounced the process of remyelination, which may be associated with a significant decrease in the number of oligodendrocytes.
Prolonged and severe demyelination occurs the death of the axons, leading to the emergence of persistent symptoms. During the damage of oligodendrocytes and myelin releasing large amounts of autoantigens, giving impetus to further development of the autoimmune process. Regulatory mechanisms that ensure the normal balance of Pro — and anti-inflammatory cytokines and timely suppression of the immune response, are in multiple sclerosis insolvent, which is responsible for the progression of the pathological process.
The evolution of the plaques characteristic of cyclicity. Reaggravation is manifested by inflammation at the periphery of the zone of gliosis, the lesion increases in size. Along with this there are new seats, and some can regress. The lesions range from several millimeters to several centimeters. They are formed around blood vessels (venules). Usually the lesions are located periventrikuljarnoj — front and rear horns of the lateral ventricles, supraventrikuliarna, the corpus callosum. Often they are localized in the brain stem and cerebellum, the cervical-thoracic spinal cord, roots of the cranial nerves, can be located also in the entrance area of roots in the spinal cord. In the case of a far advanced process of the lesions can spread to the gray matter of the brain. In addition to focal changes, multiple sclerosis inherent and diffuse signs of inflammation in the membranes, atrophy and gliosis of the white matter.
Conclusion
Thus, we can speak of the existence of a genetic predisposition to multiple sclerosis. It is determined by the combined effect of a number of related genes of the immune response, leading of which are major histocompatibility complex genes. It is assumed that the inheritance of specific alleles of these genes, in collaboration with a number of natural and environmental factors can generate an increased or decreased susceptibility to the effects of the immune system specific etiological factor, "trigger" pathogenetic cascade of multiple sclerosis, for example — a hypothetical viral agent.
References:
Schmidt T., Yahno A. N. Multiple Sclerosis. - 2012. - Р. 20-24.
Шевченко П. П. Распространенность и клиническая характеристика рассеянного склероза в Ставропольском Крае. Автореферат. - Новосибирск, 1992.
Multiple Sclerosis and heredity/Information and educational portal Scientific and Practical Center of IHB RAS. - 2013. Чотчаева А. А., Шевченко П. П., Карпов С. М. Наследственная предрасположенность к рассеянному склерозу//Международный студенческий научный вестник, 2015. - С. 109. Майда Ева. Справочник по рассеянному склерозу. - 1999.
Пажигова З. Б., Карпов С. М., Шевченко П. П., Бурнусус Н. И. Распространенность рассеянного склероза в мире (обзорная статья)//Международный журнал экспериментального образования. - 2014. - № 1-2. - С. 78-82.
Hamdard A. A., Mamedova A. E., Shevchenko P. P., Karpov S. M. Hyperthermia-syndrome as the debut of the development of multiple sclerosis//European Journal of Biomedical and Life Sciences. - 2015. - № 1. - Р. 10-11.
Karpov S. M., Padgigova Z. B., Karpov A. S., Vishlova I. A. Invoked visual potentials in the study of the visual analyzer in patients with diffuse sclerosisZ/Медицинский вестник Северного Кавказа. - 2015. - Т. 10, № 2 (38). - Р. 155-159.
