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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">medsovet</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинский Совет</journal-title><trans-title-group xml:lang="en"><trans-title>Meditsinskiy sovet = Medical Council</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2079-701X</issn><issn pub-type="epub">2658-5790</issn><publisher><publisher-name>REMEDIUM GROUP Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21518/2079-701X-2015-10-63-65</article-id><article-id custom-type="elpub" pub-id-type="custom">medsovet-274</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ДЕМИЕЛИНИЗИРУЮЩИЕ ЗАБОЛЕВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>DEMYELINATING DISEASES</subject></subj-group></article-categories><title-group><article-title>Вопросы тактики ведения больных с труднокурабельным ремитирующим рассеянным склерозом</article-title><trans-title-group xml:lang="en"><trans-title>Questions of management of patients with hard-to-treat remitting multiple sclerosis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Попова</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Popova</surname><given-names>E. V.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мельников</surname><given-names>М. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Melnikov</surname><given-names>M. V.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бойко</surname><given-names>А. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Boiko</surname><given-names>A. N.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Муругин</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Murugin</surname><given-names>V. V.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пащенков</surname><given-names>М. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Paschenkov</surname><given-names>M. V.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-4"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Городская клиническая больница №24; Российский национальный исследовательский медицинский университет им. Н.И. Пирогова</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Сity Clinical Hospital №24; Russian National Research Medical University named after N.I. Pirogov</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Российский национальный исследовательский медицинский университет им. Н.И. Пирогова</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Neurosurgery and Medical Genetics; Russian National Research Medical University named after N.I. Pirogov</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Городская клиническая больница №24 г.; Российский национальный исследовательский медицинский университет им. Н.И. Пирогова</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Сity Clinical Hospital №24; Russian National Research Medical University named after N.I. Pirogov</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>ГНЦ «Институт иммунологии»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>the State Scientific Center "Institute of Immunology"</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2015</year></pub-date><pub-date pub-type="epub"><day>30</day><month>12</month><year>2015</year></pub-date><volume>0</volume><issue>10</issue><fpage>63</fpage><lpage>65</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Попова Е.В., Мельников М.В., Бойко А.Н., Муругин В.В., Пащенков М.В., 2015</copyright-statement><copyright-year>2015</copyright-year><copyright-holder xml:lang="ru">Попова Е.В., Мельников М.В., Бойко А.Н., Муругин В.В., Пащенков М.В.</copyright-holder><copyright-holder xml:lang="en">Popova  E.V., Melnikov  M.V., Boiko  A.N., Murugin  V.V., Paschenkov  M.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.med-sovet.pro/jour/article/view/274">https://www.med-sovet.pro/jour/article/view/274</self-uri><abstract><p>На базе Московского городского центра рассеянного склероза наблюдалось 82 больных с диагнозом «ремитирующий рассеянный склероз» (РС), получающих терапию препаратом финголимод 12 и более месяцев. Целью наблюдения была оценка эффектов препарата финголимод. У 9 из 12 больных было проведено комплексное иммунологическое обследование с целью определения субпопуляций циркулирующих T-клеток. Все пациенты находились в состоянии клинической ремиссии на момент включения в исследование. У всех больных на фоне терапии финголимодом отмечено достоверное снижение частоты обострений. Показатель тяжести состояния больных по шкале EDSS не прогрессировал на протяжении всего года наблюдения. На фоне терапии выявлено значимое снижение продукции ИЛ-17 и количество Th-17-клеток по сравнению с группой контроля, что указывает на существенное снижение активности аутоиммунного процесса. При отмене приема препарата финголимод через 6-8 нед. происходит нормализация уровня лимфоцитов в периферической крови за счет выведения препарата и отмывки рецепторов S1R. Однако если учитывать, что с отмывкой S1Р-рецепторов происходит увеличение выработки ИЛ-17 и, соответственно, повышение проницаемости ГЭБ, вероятно, правомерно называть реактивацию заболевания синдромом «рикошета», который связан прежде всего с резким увеличением ИЛ-17. Это заставляет задуматься над алгоритмом ведения больных, которым по разным причинам необходимо проведение отмены терапии препаратом финголимод.</p></abstract><trans-abstract xml:lang="en"><p>82 patients diagnosed with remitting multiple sclerosis, (MS) undergoing treatment with fingolimod were followed up for minimum 12 months at the Moscow Multiple Sclerosis Centre. The purpose of the follow-up was to evaluate the effects of fingolimod. 9 of 12 patients were subject to a comprehensive immunological examination to identify subpopulations of circulating T-cells. All patients were in clinical remission at the time of recruitment. All patients showed a significant decrease in the frequency of exacerbations during therapy with fingolimod. The disability status on the EDSS scale did not progress during the whole year of the follow-up. The therapy showed significant decrease in the production of IL-17 and the amount of TH17 cells in comparison with the control group, thus demonstrating a relevant decrease in the the autoimmune process activity. Withdrawal of fingolimod in 6-8 weeks was associated with normalization of the lymphocyte level in the peripheral blood due to drug elimination and wash-out of S1P receptors. However, given that wash-out of S1P receptors results in increased production of IL-17 and, consequently, higher BBB permeability, it is appropriate to name the disease reactivation as "rebound syndrome" which is primarily associated with a sharp increase in IL-17. This raises questions about management of patients who for various reasons need withdrawal of fingolimod therapy.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>рассеянный склероз</kwd><kwd>инвалидизация обострения</kwd><kwd>финголимод</kwd><kwd>интерлейкин-17</kwd><kwd>препараты</kwd><kwd>изменяющие течение рассеянного склероза</kwd><kwd>multiple sclerosis</kwd><kwd>fingolimod</kwd><kwd>interleukin-17</kwd><kwd>multiple sclerosis disease modifying drugs</kwd><kwd>disability</kwd><kwd>exacerbation</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Brinkmann V, Davis M, Heise C et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J. Biol. Chem., 2002. 277: 21453-21457.</mixed-citation><mixed-citation xml:lang="en">Brinkmann V, Davis M, Heise C et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J. Biol. Chem., 2002. 277: 21453-21457.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Hla T. Signaling and biological actions of sphingosine 1-phosphate. Pharmacol. Res., 2003. 47 (5): 401-407.</mixed-citation><mixed-citation xml:lang="en">Hla T. Signaling and biological actions of sphingosine 1-phosphate. Pharmacol. Res., 2003. 47 (5): 401-407.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Alvarez ST, Milstien S, Spiegel S. Autocrine and paracrine roles of sphingosine-1-phosphate. Trends Endocrinol Metab, 2007. 18: 300-7.</mixed-citation><mixed-citation xml:lang="en">Alvarez ST, Milstien S, Spiegel S. Autocrine and paracrine roles of sphingosine-1-phosphate. Trends Endocrinol Metab, 2007. 18: 300-7.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Brinkmann V. Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol Ther, 2007. 115: 84-105.</mixed-citation><mixed-citation xml:lang="en">Brinkmann V. Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol Ther, 2007. 115: 84-105.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Wheeler D, Bandaru VV, Calabresi PA, et al. A defect of sphingolipid metabolism modifies the properties of normal appearing white matter in multiple sclerosis. Brain, 2008. 131: 3092-3102.</mixed-citation><mixed-citation xml:lang="en">Wheeler D, Bandaru VV, Calabresi PA, et al. A defect of sphingolipid metabolism modifies the properties of normal appearing white matter in multiple sclerosis. Brain, 2008. 131: 3092-3102.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Kulakowska A, Zendzian-Piotrowska M, Baranowski M et al. Intrathecal increase of sphingosine 1-phosphate at early stage multiple sclerosis. Neurosci Lett., 2010. 477: 149-152.</mixed-citation><mixed-citation xml:lang="en">Kulakowska A, Zendzian-Piotrowska M, Baranowski M et al. Intrathecal increase of sphingosine 1-phosphate at early stage multiple sclerosis. Neurosci Lett., 2010. 477: 149-152.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Van Doorn R, Van Horssen J, Verzijl D et al. Sphingosine 1-phosphate receptor 1 and 3 are upregulated in multiple sclerosis lesions. Glia, 2010. 58: 1465-1476.</mixed-citation><mixed-citation xml:lang="en">Van Doorn R, Van Horssen J, Verzijl D et al. Sphingosine 1-phosphate receptor 1 and 3 are upregulated in multiple sclerosis lesions. Glia, 2010. 58: 1465-1476.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Sallusto F, Geginat J, Lanzavecchia A. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol., 2004. 22: 745-63.</mixed-citation><mixed-citation xml:lang="en">Sallusto F, Geginat J, Lanzavecchia A. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol., 2004. 22: 745-63.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Miron VE, Schubart A, Antel JP. Central nervous system-directed effects of FTY720 (fingolimod). J Neurol Sci., 2008. 274: 13-17.</mixed-citation><mixed-citation xml:lang="en">Miron VE, Schubart A, Antel JP. Central nervous system-directed effects of FTY720 (fingolimod). J Neurol Sci., 2008. 274: 13-17.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Бойко А.Н. Рекомендации по использованию препарата финголимод (Гилениа). Медицинский совет, 2012. 4: 3-10.</mixed-citation><mixed-citation xml:lang="en">Бойко А.Н. Рекомендации по использованию препарата финголимод (Гилениа). Медицинский совет, 2012. 4: 3-10.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Kappos L, O'Connor P, Radue EW et al. Long-term effects of fingolimod in multiple sclerosis: the randomized FREEDOMS extension trial. Neurology, 2015; 84(15): 1582-1591.</mixed-citation><mixed-citation xml:lang="en">Kappos L, O'Connor P, Radue EW et al. Long-term effects of fingolimod in multiple sclerosis: the randomized FREEDOMS extension trial. Neurology, 2015; 84(15): 1582-1591.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
