Альманах клинической медицины. 2015; : 121-127
ТРАНСИММУНИЗАЦИЯ В ЛЕЧЕНИИ РАССЕЯННОГО СКЛЕРОЗА
Кильдюшевский А. В., Бородин А. В., Молочков А. В., Сидорова О. П., Котов С. В.
https://doi.org/10.18786/2072-0505-2015-39-121-127Аннотация
Цель – изучить эффективность метода трансиммунизации при ремитирующем течении рассеянного склероза.
Материал и методы. В исследование вошли 15 взрослых пациентов с ремитирующим течением рассеянного склероза, из них у 14 применяли трансиммунизацию, 1 пациентке во время обострения проводили фотоферез без трансиммунизации (без инкубации мононуклеаров). Клиническая оценка эффективности лечения осуществлялась с помощью расширенной шкалы инвалидности Куртцке (EDSS). Исследовали субпопуляции лимфоцитов периферической крови, IgA, IgM, IgG, TNF-α.
Результаты. После проведения 6 курсов трансиммунизации у 70% больных наблюдалось улучшение или стабилизация процесса, у 30% отмечено дальнейшее прогрессирование заболевания. Показатель CD5+ после проведения трансиммунизации статистически достоверно повышался с 76,6 ± 4,1 до 86,0 ± 2,3% (p < 0,05), показатель HLADR+ снизился c 15,3 ± 6,5 до 8,5 ± 1,69% (р < 0,05), снизились также содержание IgG и IgМ, показатель TNF-α в периферической крови (p > 0,05). Существенных побочных эффектов, связанных с лечением, не зарегистрировано.
Заключение. Полученные данные указывают на эффективность и безопасность метода трансиммунизации при лечении рассеянного склероза. Необходимо продолжить исследование с увеличением как числа пациентов, так и времени их наблюдения.
Список литературы
1. Paty DW, Li DK. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized,
2. double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group. Neurology. 1993;43(4):662–7.
3. Berger JR, Koralnik IJ. Progressive multifocal leukoencephalopathy and natalizumab – unforeseen consequences. N Engl J Med. 2005;353(4):414–6.
4. Edelson R, Berger C, Gasparro F, Jegasothy B, Heald P, Wintroub B, Vonderheid E, Knobler R, Wolff K, Plewig G. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med. 1987;316(6):297–303.
5. Неретин ВЯ, Кильдюшевский АВ, Агафонов БВ, Гехт БМ, Сидорова ОП, Оспель- никова ТП. Фотоферез – новый метод лечения миастении. Журнал неврологии и психиатрии им. С.С. Корсакова. 2003;103 (6):11–4. Neretin VYa, Kil'dyushevskiy AV, Agafonov BV,
6. Gekht BM, Sidorova OP, Ospel'nikova TP. Fotoferez – novyy metod lecheniya miastenii [Photopheresis, a new method of treatment for myasthenia]. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2003;103(6):11–4 (in Russian).
7. Dall'Amico R, Zulian F, Montini G, Andretta B, Murer L, Rossetti F, Livi U, Zacchello G, Zacchello F. Applications of extracorporeal photochemotherapy in “non-oncological” diseases. Int J Artif Organs. 1993;16 Suppl 5:168–72.
8. Неретин ВЯ, Кильдюшевский АВ, Озе- рова ИВ, Котов СВ, Голенков АК. Способ лечения аутоиммунных заболеваний. Патент на изобретение РФ № 2159635 от 27.11.2000. Neretin VYa, Kil'dyushevskiy AV, Ozerova IV, Kotov SV, Golenkov AK. Sposob lecheniya autoimmunnykh zabolevaniy [The art of treatment of autoimmune diseases]. The patent of RF of an invention No. 2159635 from 27.11.2000 (in Russian).
9. Aringer M, Graninger WB, Smolen JS, Kiener HP, Steiner CW, Trautinger F, Knobler R. Photopheresis treatment enhances CD95 (fas) expression in circulating lymphocytes of patients with systemic sclerosis and induces apoptosis. Br J Rheumatol. 1997;36(12): 1276–82.
10. Poehlau D, Rieks M, Postert T, Westerhausen R, Busch S, Hoffmann K, Altmeyer P, Przuntek H. Photopheresis – a possible treatment of multiple sclerosis?: report of two cases. J Clin Apher. 1997;12(3):154–5.
11. Besnier DP, Chabannes D, Mussini JM, Dupas B, Esnault VL. Extracorporeal photochemotherapy for secondary chronic progressive multiple sclerosis: a pilot study. Photodermatol Photoimmunol Photomed. 2002;18(1):36–41.
12. Rostami AM, Sater RA, Bird SJ, Galetta S, Farber RE, Kamoun M, Silberberg DH, Grossman RI, Pfohl D. A double-blind, placebo-controlled trial of extracorporeal photopheresis in chronic progressive multiple sclerosis. Mult Scler. 1999;5(3):198–203.
13. Kaser A, Deisenhammer F, Berger T, Tilg H. Interferon-beta 1b augments activation-induced T-cell death in multiple sclerosis patients. Lancet. 1999;353(9162):1413–4.
14. Кильдюшевский АВ, Молочков ВА, Ольшанский АЯ, Молочков АВ, Фомин АМ, Гордиевская МС, Карзанов ОВ, Петренко ЕВ. Адоптивная иммунотерапия Т-клеточных лимфом кожи на основе экстракорпорального фотофереза. Российский журнал кож-ных и венерических болезней. 2010;(1): 4–10. Kil'dyushevskiy AV, Molochkov VA, Ol'shanskiy AYa, Molochkov AV, Fomin AM, Gordievskaya MS, Karzanov OV, Petrenko EV. Adoptivnaya immunoterapiya T-kletochnykh limfom kozhi na osnove ekstrakorporal'nogo fotofereza [Adoptive immune therapy of skin T-cell lymphomas based on extracorporeal photopheresis]. Rossiyskiy zhurnal kozhnykh i venericheskikh bolezney. 2010;(1):4–10 (in Russian).
15. Berger CL, Hanlon D, Kanada D, Girardi M, Edelson RL. Transimmunization, a novel approach for tumor immunotherapy. Transfus Apher Sci. 2002;26(3):205–16.
16. Bladon J, Taylor PC. Early reduction in number of T cells producing proinflammatory cytokines, observed after extracorporeal photopheresis, is not linked to apoptosis induction. Transplant Proc. 2003;35(4):1328–32.
17. Berger CL, Xu AL, Hanlon D, Lee C, Schechner J, Glusac E, Christensen I, Snyder E, Holloway V, Tigelaar R, Edelson RL. Induction of human tumor-loaded dendritic cells. Int J Cancer. 2001;91(4):438–47.
Almanac of Clinical Medicine. 2015; : 121-127
TRANSIMMUNIZATION IN THE TREATMENT OF MULTIPLE SCLEROSIS
Kil'dyushevskiy A. V., Borodin A. V., Molochkov A. V., Sidorova O. P., Kotov S. V.
https://doi.org/10.18786/2072-0505-2015-39-121-127Abstract
Aim: To study efficacy of the trans-immunization method in remitting-relapsing multiple sclerosis.
Materials and methods: The study included 15 adult patients with remitting multiple sclerosis, in 14 of whom transimmunization was used; 1 female patient during the relapse was administered photopheresis without transimmunization (without mononuclear incubation). Clinical assessment of treatment efficacy was performed with Kurtzke Expended Disability Scale (EDSS). Also, subpopulations of peripheral blood lymphocytes and levels of IgA, IgM, IgG, TNF-α were measured.
Results: After 6 courses of transimmunization, the disease process was improved or stabilized in 70% of patients, whereas 30% of patients progressed further. After transimmunization, CD5+ counts significantly increased from 76.6 ± 4.1 to 86.0 ± 2.3% (p < 0.05), HLA-DR+ decreased from 15.3 ± 6.5 to 8.5 ± 1.69% (р < 0.05), the levels of IgG, IgМ and TNF-α in peripheral blood also decreased (p > 0.05). No treatment-related adverse effects were registered.
Conclusion: The data obtained shows efficacy and safety of the transimmunization method in the treatment of multiple sclerosis. It is necessary to continue studies in larger patient numbers, as well as with longer follow-up.
Key words:
References
1. Paty DW, Li DK. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized,
2. double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group. Neurology. 1993;43(4):662–7.
3. Berger JR, Koralnik IJ. Progressive multifocal leukoencephalopathy and natalizumab – unforeseen consequences. N Engl J Med. 2005;353(4):414–6.
4. Edelson R, Berger C, Gasparro F, Jegasothy B, Heald P, Wintroub B, Vonderheid E, Knobler R, Wolff K, Plewig G. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med. 1987;316(6):297–303.
5. Neretin VYa, Kil'dyushevskii AV, Agafonov BV, Gekht BM, Sidorova OP, Ospel'- nikova TP. Fotoferez – novyi metod lecheniya miastenii. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2003;103 (6):11–4. Neretin VYa, Kil'dyushevskiy AV, Agafonov BV,
6. Gekht BM, Sidorova OP, Ospel'nikova TP. Fotoferez – novyy metod lecheniya miastenii [Photopheresis, a new method of treatment for myasthenia]. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2003;103(6):11–4 (in Russian).
7. Dall'Amico R, Zulian F, Montini G, Andretta B, Murer L, Rossetti F, Livi U, Zacchello G, Zacchello F. Applications of extracorporeal photochemotherapy in “non-oncological” diseases. Int J Artif Organs. 1993;16 Suppl 5:168–72.
8. Neretin VYa, Kil'dyushevskii AV, Oze- rova IV, Kotov SV, Golenkov AK. Sposob lecheniya autoimmunnykh zabolevanii. Patent na izobretenie RF № 2159635 ot 27.11.2000. Neretin VYa, Kil'dyushevskiy AV, Ozerova IV, Kotov SV, Golenkov AK. Sposob lecheniya autoimmunnykh zabolevaniy [The art of treatment of autoimmune diseases]. The patent of RF of an invention No. 2159635 from 27.11.2000 (in Russian).
9. Aringer M, Graninger WB, Smolen JS, Kiener HP, Steiner CW, Trautinger F, Knobler R. Photopheresis treatment enhances CD95 (fas) expression in circulating lymphocytes of patients with systemic sclerosis and induces apoptosis. Br J Rheumatol. 1997;36(12): 1276–82.
10. Poehlau D, Rieks M, Postert T, Westerhausen R, Busch S, Hoffmann K, Altmeyer P, Przuntek H. Photopheresis – a possible treatment of multiple sclerosis?: report of two cases. J Clin Apher. 1997;12(3):154–5.
11. Besnier DP, Chabannes D, Mussini JM, Dupas B, Esnault VL. Extracorporeal photochemotherapy for secondary chronic progressive multiple sclerosis: a pilot study. Photodermatol Photoimmunol Photomed. 2002;18(1):36–41.
12. Rostami AM, Sater RA, Bird SJ, Galetta S, Farber RE, Kamoun M, Silberberg DH, Grossman RI, Pfohl D. A double-blind, placebo-controlled trial of extracorporeal photopheresis in chronic progressive multiple sclerosis. Mult Scler. 1999;5(3):198–203.
13. Kaser A, Deisenhammer F, Berger T, Tilg H. Interferon-beta 1b augments activation-induced T-cell death in multiple sclerosis patients. Lancet. 1999;353(9162):1413–4.
14. Kil'dyushevskii AV, Molochkov VA, Ol'shanskii AYa, Molochkov AV, Fomin AM, Gordievskaya MS, Karzanov OV, Petrenko EV. Adoptivnaya immunoterapiya T-kletochnykh limfom kozhi na osnove ekstrakorporal'nogo fotofereza. Rossiiskii zhurnal kozh-nykh i venericheskikh boleznei. 2010;(1): 4–10. Kil'dyushevskiy AV, Molochkov VA, Ol'shanskiy AYa, Molochkov AV, Fomin AM, Gordievskaya MS, Karzanov OV, Petrenko EV. Adoptivnaya immunoterapiya T-kletochnykh limfom kozhi na osnove ekstrakorporal'nogo fotofereza [Adoptive immune therapy of skin T-cell lymphomas based on extracorporeal photopheresis]. Rossiyskiy zhurnal kozhnykh i venericheskikh bolezney. 2010;(1):4–10 (in Russian).
15. Berger CL, Hanlon D, Kanada D, Girardi M, Edelson RL. Transimmunization, a novel approach for tumor immunotherapy. Transfus Apher Sci. 2002;26(3):205–16.
16. Bladon J, Taylor PC. Early reduction in number of T cells producing proinflammatory cytokines, observed after extracorporeal photopheresis, is not linked to apoptosis induction. Transplant Proc. 2003;35(4):1328–32.
17. Berger CL, Xu AL, Hanlon D, Lee C, Schechner J, Glusac E, Christensen I, Snyder E, Holloway V, Tigelaar R, Edelson RL. Induction of human tumor-loaded dendritic cells. Int J Cancer. 2001;91(4):438–47.
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