Microbial agents as triggers of developing multiple sclerosis

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Abstract

Multiple sclerosis (MS) currently represents a pressing medical and social issue. This is due to the high prevalence of this pathology among neurological diseases preferentially affecting young people and subsequent rapid disability. This disease still remains a mystery for medicine due to its ambiguous etiology, polymorphism of clinical manifestations and unstable course. Despite the marked development of modern instrumental diagnostic methods, pathognomonic signs have not yet been identified for multiple sclerosis allowing to diagnose the disease with high accuracy at early stages. At the moment, we may 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 due to combination of external factors and hereditary predisposition, which causes altered immune tolerance. The polygenic theory of MS is most substantiated, which implies that the genotype of MS patients consists of many genes, each of which contributes to the disease development. More than 100 genes associated with MS have been identified, among which a special place is taken 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: 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 (IL-12A) and others. However, to uncover genetic predisposition, it is necessary to experience external trigger factors. The activation of demyelinating process is quite often initiated by various infectious agents, among which the most studied are Epstein–Barr virus, John Cunningham virus, acute encephalomyelitis virus, and human endogenous retroviruses. Intestinal microbiota altered by Candida albicans, Staphylococcus aureus, Acinetobacter calcoaceticus, Bacteroides, Proteobacteria and Firmicutes deserved special attention in developing neurodegenerative disorders. Such an imbalance profoundly affects immune and nervous system functioning, taking part in neurogenesis, myelination, activation of cellular and humoral immune responses. Here we review and analyze the latest data accumulated in Russian and foreign literature regarding the study of the MS epidemiological features, as well as microbiological risk factors for disease development.

About the authors

A. V. Lapshtaeva

Ogarev Mordovia State University

Author for correspondence.
Email: av_lapshtaeva@mail.ru

Anna V. Lapshtaeva - Associate Professor, Department of Immunology, Microbiology and Virology, Ogarev Mordovia State University.

430005, Republic of Mordovia, Saransk, Bolshevistskaya str., 68.

Phone: +7 927 177-35-55.

Russian Federation

Yu. G. Abrosimova

Pirogov Russian National Research Medical Universityу

Email: fake@neicon.ru

Resident Physician, Department of Clinical Laboratory Diagnostics, Faculty of Additional Professional Education, Pirogov Russian National Research Medical University.

Moscow.

Russian Federation

T. Ya. Eremkina

Ogarev Mordovia State University

Email: fake@neicon.ru

Resident Physician, Department of Nervous Diseases and Psychiatry of Medical Institute, Ogarev Mordovia State University.

Saransk.

Russian Federation

Yu. A. Kostina

Ogarev Mordovia State University

Email: fake@neicon.ru

Associate Professor, Department of Immunology, Microbiology and Virology, Ogarev Mordovia State University.

Saransk.

Russian Federation

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. doi: 10.15789/2220-7619-2019-3-4-504-522
  3. Акопян К.Г., Благовестная Е.И., Иванов С.В. Структура и развитие рассеянного склероза в г. Симферополь Республики Крым за 2017–2019 гг. // Modern Science. 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. 53, № 9. С. 1035–1041. doi: 10.7868/S0016675817090053
  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. doi: 10.17116/jnevro2017117226-9
  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 // Acta Naturae. 2019. Т. 11, № 4. С. 4–12. doi: 10.32607/20758251-2019-11-4-4-12
  9. Кулакова О.Г., 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. doi: 10.17116/jnevro201611610210–15
  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. doi: 10.31301/2221-6197.bmcs.2018-40
  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. doi: 10.31684/2541-8475.2017.1(5).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. doi: 10.30809/phe.2.2018.4
  15. Ascherio A., Munger K.L., White R., Köchert K., Simon K.C., Polman C.H., Freedman M.S., Hartung H.P., Miller D.H., Montalbán X., Edan G., Barkhof F., Pleimes D., Radü E.W., Sandbrink R., Kappos L., Pohl C. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurology, 2014, vol. 71, no. 3, pp. 306–314. doi: 10.1001/jamaneurol.2013.5993
  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. doi: 10.1126/science.1198469
  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 Mol. Med., 2019, vol. 26, no. 3, pp. 296– 310. doi: 10.1016/j.molmed.2019.11.003
  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. Hum. Genet., 2015, vol. 134, no. 11, pp. 1143–1162. doi: 10.1007/ s00439-015-1601-2
  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. Proc. Natl. Acad. Sci. USA, 2017, vol. 114, no. 40, pp. 10719–10724. doi: 10.1073/pnas.1711233114
  20. Cekanaviciute E., Yoo B.B., Runia T.F., Debelius J.W., Singh S., Nelson C.A., Kanner R., Bencosme Y., Lee Y.K., Hauser S.L., Crabtree-Hartman E., Sand I.K., Gacias M., Zhu Y., Casaccia P., Cree B.A., Knight R., Mazmanian S.K., Baranzini E. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc. Natl. Acad. Sci. USA, 2017, vol. 114, no. 40, pp. 10713–10718. doi: 10.1073/pnas.1711235114
  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. Curr. Top. Med. Chem., 2020, vol. 20, no. 13, pp. 1142–1153. doi: 10.2174/15 68026620666200413091101
  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. Sci. Rep., 2016, vol. 6: 28484. doi: 10.1038/srep28484
  23. Gaboriau-Routhiau V., Rakotobe S., Lécuyer E., Mulder I., Lan A., Bridonneau C., Rochet V., Pisi A., De Paepe M., Brandi G., Eberl G., Snel J., Kelly D., Cerf-Bensussan N. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity, 2009, vol. 31, no. 4, pp. 677–689. doi: 10.1016/j.immuni.2009.08.020
  24. Guzik T.J., Skiba D.S., Touyz R.M., Harrison D.G. The role of infiltrating immune cells in dysfunctional adipose tissue.Cardiovasc. Res., 2017, vol. 113, no. 9, pp. 1009–1023. doi: 101093/cvr/cvx108
  25. Hohlfeld R. ECTRIMS lecture: future challenges in MS. Multiple Sclerosis, 2009, vol. 16, no. 1, pp. 3–14. doi: 10.1177/1352458509357355
  26. Jangi S., Gandhi R., Cox L.M., Ning L.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. Nat. Commun., 2016, vol. 7, pp. 12–15. doi: 10.1038/ncomms1201542
  27. Kha M.T., Wallin M., Culpepper W., Nichols E., Bhutta Z., Gebrehiwot T., Hay S., Khalil I., Krohn K.J., Liang X., Naghavi M., Mokdad A., Nixon M., Reiner R., Sartorius B., Smith M., Topor-Madry R., Werdecker A., Vos T., Feigin V., Murray C.J. Global regional, and national burden of multiple sclerosis 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol., 2019, vol. 18, pp. 269–285. doi: 10.1016/S1474-4422(18)30443-5
  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 Mol. Med., 2018, vol. 24, pp. 379–394. doi: 10.1016/j.molmed
  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. Leray E., Moreau T., Fromont A., Edan G. Epidemiology of multiple sclerosis. Rev. Neurol. (Paris), 2016, vol. 172, no. 1, pp. 3–13. doi: 10.1016/j.neurol.2015.10.006
  31. Leray E., Vukusic S., Debouverie M., Clanet M., Brochet B., Sèze J., Zéphir H., Defer G., Lebrun-Frenay C., Moreau T., Clavelou P., Pelletier J., Berger E., Cabre P., Camdessanché J.F., Kalson-Ray S., Confavreux C., Edan G. Excess mortality in patients with multiple sclerosis starts at 20 years from clinical onset: data from a large-scale French observational study. PLoS One, 2015, vol. 10, no. 7: e0132033. doi: 10.1371/journal.pone.0132033
  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: e02513. doi: 10.1128/mBio.02513-14
  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. Mol. Immunol., 2016, vol. 69, pp. 7–12. doi: 10.1016/j.molimm.2015.11.007
  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. J. Cell. Physiol., 2020, vol. 235, no. 7, pp. 5847–5855. doi: 10.1002/jcp.29533
  35. Saroukolaei S.A., Ghabaee M., Shokri H., Badiei A., Ghourchian S. The role of Candida albicans in the severity of multiple sclerosis. Mycoses, 2016, vol. 59, no. 11, pp. 697–704. doi: 10.1111/myc.12489
  36. Sawser S., Franklin R.J., Ban M. Multiple sclerosis genetics. Lancet Neurol., 2014, vol. 13, no. 7, pp. 700–709. doi: 10.1016/S1474-4422(14)70041-9
  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. 184–192. doi: 10.1212/WNL.0b013e31829a3388
  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. doi: 10.4103/ijmr.IJMR_1225_15
  39. Wacleche V.S., Goulet J.P., Gosselin A., Monteiro P., Soudeyns H., Fromentin R., Jenabian M.A., Vartanian S., Deeks S.G., Chomont N., Routy J.P., Ancuta P. New insights into the heterogeneity of Th17 subsets contributing to HIV-1 persistence during antiretroviral therapy. Retrovirology, 2016, vol. 13, no. 1: 59. doi: 10.1186/s12977-016-0293-6
  40. Xiao D., Ye X., Zhang N., Ou M., Guo C., Zhang B., Liu Y., Wang M., Yang G., Jing C. A meta-analysis of interaction between Epstein–Barr virus and HLADRB1*1501 on risk of multiple sclerosis. Sci. Rep., 2015, vol. 5: 18083. doi: 10.1038/srep18083
  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. doi: 10.3389/fmicb.2017.02596
  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 IFNγ or IL-10 and are regulated by IL-1β. Nature, 2012, vol. 484, no. 7395, pp. 514–518. doi: 10.1038/nature10957

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