MICROBIAL AGENTS AS TRIGGERS OF MULTIPLE SCLEROSIS DEVELOPMENT


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Abstract

Multiple sclerosis (MS) is currently an urgent medical and social problem. This is due to the high prevalence of this pathology among neurological diseases with the predominant lesion of young people and subsequent rapid disability. This disease still remains a mystery for medicine in view of its ambiguous etiology, polymorphism of clinical manifestations and unstable course. Despite the significant development of modern instrumental diagnostic methods, for multiple sclerosis, pathognomonic signs have not yet been identified that make it possible to diagnose the disease with high accuracy in the early stages. At the moment, we can only say with confidence that MS is a neurodegenerative disease accompanied by rapid demyelination and death of nerve cells.  Complex and diverse pathogenetic mechanisms suggest a multifactorial nature of the disease, which develops with a combination of external factors and hereditary predisposition, which causes a violation of immune tolerance. The most substantiated is the polygenic theory of MS, which implies that the genotype of MS patients consists of many genes, each of which contributes to the development of the disease. More than 100 genes associated with MS have been identified, among which a special place is occupied by the HLA system (human leukocyte antigen), which controls the interaction of immunocompetent cells and carries out an immune response. In addition, new candidate genes have been identified that contribute to the development of MS: genes of interleukin 2 and 7 receptors (IL-2R, IL-7R), differentiation cluster 6 (CD6) and 58 (CD58), tumor necrosis factor α, interferon regulatory factor 8 (IRF8), interleukin 12А (IL12A) and others.However, to realize genetic predisposition, the influence of external trigger factors is necessary. The activation of the demyelinating process is quite often initiated by various infectious agents, among which the most studied viruses are Epstein-Barr, John-Cunningham, acute encephalomyelitis, and human endogenous retroviruses. Particular attention in the development of neurodegenerative disorders deserves a change in the intestinal microbiota, by counting microorganisms such as Candida albicans, Staphylococcus aureus, Acinetobacter calcoaceticus, Bacteroides, Proteobacteria and Firmicutes. This imbalance has a significant effect on the functioning of the immune and nervous systems, taking part in the processes of neurogenesis, myelination, activation of the cellular and humoral types of the immune response. This review presents and analyzes latest data from domestic and foreign literature on the study of the epidemiological features of MS, as well as microbiological risk factors for the development of the disease.

About the authors

Yu. Froltsova

Email: yulya.froltsova@mail.ru

student of Medical Institute Federal State Budgetary Educational Institution of Higher Education "National Research Ogarev Mordovia State University".

A. Lapshtaeva

Author for correspondence.
Email: av_lapshtaeva@mail.ru

Docent of Department of Immunology, microbiology and Virology, Federal State Budgetary Educational Institution of Higher Education "National Research Ogarev Mordovia State University"

Russian Federation

T. Evseeva

Email: tanya.eremkina7@yandex.ru

Resident of the Department of Nervous Diseases and Psychiatry of Medical Institute Federal State Budgetary Educational Institution of Higher Education "National Research Ogarev Mordovia State University"

Y. Kostina

Email: bazunova.2013@mail.ru

Docent of Department of Immunology, microbiology and Virology, Federal State Budgetary Educational Institution of Higher Education "National Research Ogarev Mordovia State University".

References

  1. Абдурасулова И.Н., Ермоленко Е.И., Мацулевич А.В., Абдурасулова К.О., Тарасова Е.А., Кудрявцев И.В., Бисага Г.Н., Суворов А.Н., Клименко В.М. Влияние пробиотических энтерококков и глатирамера ацетата на тяжесть экспериментального аллергического энцефаломиелита у крыс. Российский физиологический журнал им. И.М. Сеченова, 2016, Т. 102, №4, С. 463-479.
  2. Абдурасулова И.Н., Тарасова Е.А., Кудрявцев И.В., Негореева И.Г., Ильвес А.Г., Серебрякова М.К., Ермоленко Е.И., Ивашкова Е.В., Мацулевич А.В., Татаринов А.Е., Столяров И.Д., Клименко В.М., Суворов А.Н. Состав микробиоты кишечника и популяций циркулирующих Тh-клеток у пациентов с рассеянным склерозом. Инфекция и иммунитет, 2019, Т. 9, № 3, С. 504-522.
  3. Акопян К.Г., Благовестная Е.И., Иванов С.В. Структура и развитие рассеянного склероза в г. Симферополь республики Крым за 2017-2019 гг. ModernScience, 2020, Т.2, № 1, С. 202-207.
  4. Баринский И.Ф., Гребенникова Т.В., Альховский С.В., Кочергин-Никитский К.С., Сергеев О.В., Грибенча С.В., Раев С.А. Молекулярно-генетическая характеристика вируса, выделенного от больных острым энцефаломиелитом человека и множественным склерозом. Вопросы вирусологии, 2015, Т. 60, № 4, С. 14-18.
  5. Быкадоров П.А., Опарина Н.Ю., Фридман М.В.,Макеев В.Ю. Локусы, влияющие на экспрессию антигенов HLA в участке 14-й хромосомы, ассоциированном с развитием рассеянного склероза, и функции расположенных в них генов. Генетика, 2017, Т. 5, № 9, С. 1035-1041.
  6. Гончарова З.А., Беловолова Р.А., Мегерян В.А. Клинико-иммунологические особенности рассеянного склероза на фоне реактивации персистирующей герпесвирусной инфекции. Саратовский научно-медицинский журнал, 2018, Т. 14, № 1, С. 126-132.
  7. Гончарова З.А., Ужахов Р.М. Анализ распространенности и факторы риска развития рассеянного склероза в республике Ингушетия. Журнал неврологии и психиатрии им. C.C. Корсакова, 2017, Т. 117, № 2, С. 6-9.
  8. Захарова М.Ю., Белянина Т.А., Соколов А.В., Киселев И.С., Мамедов А.Э. Вклад генов главного комплекса гистосовместимости класса II в предрасположенность к аутоиммунным заболеваниям. ActaNaturae, 2019, Т. 11, № 4, С. 4-12.
  9. Кулакова О.Г.1, Башинская В.В., Царева Е.Ю., Бойко А.Н., Фаворова О.О., Гусев Е.И. Анализ ассоциации полиморфизма генов, кодирующих рецепторы цитокинов, с клиническими характеристиками рассеянного склероза. Журнал неврологии и психиатрии им. C.С. Корсакова, 2016, Т. 10, № 2, С. 10-15.
  10. Лорина Л.В., Джапаралиева Н.Т., Буршинов А.О. Показатели качества жизни при различных типах течения рассеянного склероза. Медицина, 2017, Т. 5, № 2, С. 88-96.
  11. Насибуллин Т.Р., Туктарова И.А., Эрдман В.В., Тимашева Я.Р., Заплахова О.В., Бахтиярова К.З., Мустафина О.Е. Ассоциации полиморфных ДНК-маркеров с рассеянным склерозом в этнической группе башкир. Биомика, 2018, Т. 10, № 3, С. 319-326.
  12. Семин Е.В, Блохин Б.М, Каграманова К.Г, Майорова О.А. Система HLA: строение, функции, очевидная и возможная связь с аутоиммунными и атопическими заболеваниями. Лечебное дело, 2012, № 1, С. 4-9.
  13. Смагина И.В., Ельчанинова С.А., Бодрова Ю.В. Связь полиморфизма генов иммунной системы с особенностями течения рассеянного склероза. Бюллетень медицинской науки, 2017, № 1, С. 70-74.
  14. Толкушин А.Г., Смирнова А.В., Давыдовская М.В., Ермолаева Т.Н., Андреев Д.А., Кокушкин К.А. Бремя рассеянного склероза в России и Европе: где больше? Фармакоэкономика: теория и практика, 2018, Т. 6, №2, С. 25-30.
  15. Alharbi F.M. Update in vitamin D and multiple sclerosis. Neurosciences (Riyadh), 2015, Vol. 20, no. 4, pp. 329–335.
  16. Atarashi K., Tanoue T., Shima T.,Imaoka A., Kuwahara T., Momose Y., Cheng G., Yamasaki S., Saito T., Ohba Y., Taniguchi T., Takeda K., Hori S., Ivanov I.I., Umesaki Y., Itoh K., Honda K. Induction of colonic regulatory T cells by indigenous Clostridium species. Science, 2011, Vol. 331, no. 6015, pp. 337–341.
  17. Bar-Or A., Pender M., Khanna R., Steinman L., Hartung H.P., Maniar T., Croze E., Aftab B.T., Giovannoni G., Joshi M.A. Epstein-Barr virus in multiple sclerosis: theory and emerging immunotherapies. Trends in Molecular Medicine, 2019, Vol. 26, no. 3, pp. 296-310.
  18. Bashinskaya V.V., Kulakova O.G., Boyko A.N., Favorov A. V., Favorova O.O. A review of genome-wide association studies for multiple sclerosis: classical and hypothesis-driven approaches. Human Genetics, 2015, Vol. 134, no.11, pp. 1143-1162.
  19. Berer K., Gerdes L.A., Cekanaviciute E.,Jia X., Xiao L., Xia Z., Liu C., Klotz L., Stauffer U., Baranzini S.E., Kümpfel T., Hohlfeld R., Krishnamoorthy G., Wekerle H. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proceedings of the National Academy of Sciences of the United States of America, 2017, Vol. 114, no. 40, pp.10719-10724.
  20. Bitarafan S., Saboor-Yaraghi A., Sahraian M.A.,Soltani D., Nafissi S., Togha M., Beladi Moghadam N., Roostaei T., Mohammadzadeh Honarvar N. and Harirchian M.-H. Effect of vitamin A supplementation on fatigue and depression in multiple sclerosis patients: a double-blind placebo-controlled clinical trial. Iranian Journal of Allergy, Asthma and Immunology, 2016, Vol. 15, no. 1, pp. 13-19.
  21. Chandra S., Alam M.T., Dey J., Sasidharan C.P., Ray U., Srivastava A.K., Gandhi S., Tripathi P.P. Healthy gut, dealthy brain: the gut microbiome in neurodegenerative disorders. Current Topics in Medicinal Chemistry, 2020, Vol. 20, no. 13, pp. 1142-1153.
  22. Chen J., Chia N., Kalari K.R.,Yao J.Z., Novotna M., Soldan M.P., Luckey D.H., Marietta E.V., Jeraldo P.R., Chen X., Weinshenker B.G., Rodriguez M., Kantarci O.H., Nelson H., Murray J.A., Mangalam A.K. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Scientific Reports, 2016, Vol. 6, no. 28484.
  23. Christakos S., Dhawan P., Verstuyf A.,Verlinden L., Carmeliet G. . Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiological Reviews, 2016, Vol. 96, no. 1, pp. 365-408.
  24. Guerrero-García J.D., Castañeda-Moreno V.A., Torres-Carrillo N,Muñoz-Valle J.F., Bitzer-Quintero O.K., Ponce-Regalado M.D., Mireles-Ramírez M.A., Valle Y., Ortuño-Sahagún D . Interleukin-17A levels vary in relapsing-remitting multiple sclerosis patients in association with their age, treatment and the time of evolution of the disease. NeuroImmunoModulation, 2016, Vol. 23, no. 1, pp. 8–17.
  25. Hashemi R., Hosseini-Asl S.S., Arefhosseini S.R.,Morshedi M. The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives. PLoS One, 2020, Vol. 15, no. 4, e0231145.
  26. Jangi S., Gandhi R., Cox L.M., Ning Li N., Glehn F., Yan R., Patel B., Mazzola M.A., Liu S., Glanz B.L., Cook S., Tankou S., Stuart F., Melo K., Nejad P., Smith K., Topçuolu B.D., Holden J., Kivisäkk P., Chitnis T., De Jager P.L., Quintana F.J., Gerber G.K., Bry L., Weiner H.L. Alterations of the human gut microbiome in Multiple sclerosis. Nature Communications, 2016, Vol. 7, pp. 12-15.
  27. Kampman M.T., Steffensen L.H., Mellgren S.I., Jorgensen L. Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial.Multiple Sclerosis Journal, 2012, Vol. 18, no. 8, pp. 1144–1151.
  28. Kuri P., Nath A., Créange A.,Dolei A., Marche P., Gold J., Giovannoni G., Hartung H.P., Perron H. Human endogenous retroviruses in neurological diseases. Trends in Molecular Medicine, 2018, Vol. 24, pp. 379–394.
  29. Kurtzke J.F. Multiple sclerosis in time and space geographic clues to cause. J. Neurovirol. 2000, Vol. 6, no. 2, pp. 134-140.
  30. Laursen J.H., Søndergaard H.B., Sørensen P.S.,Sellebjerg F., Oturai A.B. Association between age at onset of multiple sclerosis and vitamin D level–related factors. Neurology, 2016, Vol. 86, no. 1, pp. 88–93.
  31. Leray E., Moreau T., Fromont A., Edan G. Epidemiology of multiple sclerosis. Rev Neurol (Paris), 2016, Vol. 172, no. 1, pp. 3-13.
  32. Linden J.R., Ma Y., Zhao B.,Harris J.M., Rumah K.R., Schaeren-Wiemers N., Vartanian T. Clostridium perfringens epsilon toxin causes selective death of mature oligodendrocytes and central nervous system demyelination. Mbio, 2015, Vol. 6, no. 3, e0513–14.
  33. Lyndsey J.W., de Gannes S.L., Pate K.A.,Zhao X. Antibodies specific for Epstein-Barr virus nuclear antigen-1 cross-react with human heterogeneous nuclear ribonucleoprotein L. Molecular immunology, 2016, Vol.69, pp. 7-12.
  34. Mazzoni E., Bononi I., Pietrobon S., Torreggiani E., Rossini M., Pugliatti M., Casetta I., Castellazzi M., Granieri E., Guerra G., Martini F., Tognon M. Specific antibodies reacting to JC polyomavirus capsid protein mimotopes in sera from multiple sclerosis and other neurological diseases-affected patients. Journal of Cellular Physiology, 2020, Vol. 235, no.7, pp. 5847-5855.
  35. Mosayebi G., Ghazavi A., Ghasami K., Jand Y., Kokhaei P. Therapeutic effect of vitamin D3 in multiple sclerosis patients. Immunological Investigation, 2011, Vol. 40, no. 6, pp. 627-639.
  36. Sawser S., Franklin R.J., Ban M. Multiple sclerosis genetics. Lancet Neurol, 2014, Vol. 13, no. 7, pp. 700-709.
  37. Scalfari A., Knappertz V., Cutter G., Goodin D.S., Ashton R., Ebers G.C. Mortality in patients with multiple sclerosis. Neurology, 2013, Vol. 81, no.2, pp. 184-92.
  38. Shahbazi M., Sadeghi S., Abadi A., Koochaki1 M., Amiri H., Kohansal R., Baghbanian S.M., Zamani M. Combination of interleukin-10 gene promoter polymorphisms with HLA-DRB1*15 allele is associated with multiple sclerosis. Indian J Med Res, 2017, Vol. 145, no. 6, pp. 746-752.
  39. Simon K.C., van der Mei I.A.F, Munger K.L., Ponsonby A., Dickinson J., Dwyer T., Sundström P., Ascherio A. Combined effects of smoking, anti-EBNA antibodies, and HLA-DRB1*1501 on multiple sclerosis risk. Neurology, 2010, Vol. 74, no. 17, pp. 1365-1371.
  40. Wrzosek M., Łukaszkiewicz J., Wrzosek M., Jakubczyk A., Matsumoto H., Piątkiewicz P., Radziwoń-Zaleska M., Wojnar M., Nowicka G. Vitamin D and the central nervous system. Pharmacological reports, 2013, Vol. 65, no. 2, pp. 271-278.
  41. Yamashita M., Ukibe K., Matsubara Y., Hosoya T., Sakai F., Kon S., Arima Y., Murakami M., Nakagawa H., Miyazaki T. Lactobacillus helveticus SBT2171 attenuates experimental autoimmune encephalomyelitis in mice. Front. Microbiol., 2018, vol. 8, 2596.
  42. Zielinski C.E., Mele F., Aschenbrenner D., Jarrossay D., Ronchi F., Gattorno M., Monticelli S., Lanzavecchia A., Sallusto F. Pathogen-induced human T(H)17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. Nature, 2012, Vol. 484, no.7395, pp.514–518.

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Copyright (c) 2021 Froltsova Y., Lapshtaeva A., Evseeva T., Kostina Y.

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