Альманах клинической медицины. 2016; 44: 317-323
ВЛИЯНИЕ НЕЙТРАЛИЗУЮЩИХ АНТИТЕЛ К ИНТЕРФЕРОНУ-БЕТА НА ПРОГРЕССИРОВАНИЕ РАССЕЯННОГО СКЛЕРОЗА
https://doi.org/10.18786/2072-0505-2016-44-3-317-323Аннотация
Актуальность. У больных рассеянным склерозом нейтрализующие антитела (НАТ) оказывают влияние на эффективность интерферонотерапии, однако оно расценивается неоднозначно. Синтез НАТ определяется несколькими факторами: продолжительностью рассеянного склероза и его течением, частотой и длительностью введения интерферона, формулой препарата интерферона-бета (ИФН-β), генотипом пациента. Отмечено, что титры НАТ меняются с течением времени. Цель – оценить уровень НАТ к ИФН-β- 1b у больных рассеянным склерозом и изучить взаимосвязь с прогрессированием заболевания. Материал и методы. Обследована сыворотка крови 83 пациентов с рассеянным склерозом после длительной терапии ИФН-β-1b, проведена реакция по выявлению НАТ методом оценки цитопатического эффекта. Результаты. НАТ выявлены у 63,9% (53 из 83) пациентов с длительностью применения ИФН-β-1b 33,3±17,6 месяца. Все НАТ-положительные пациенты получали высокодозную терапию ИФН-β. В группе пациентов с титрами НАТ больше 800 ЛЕ (n=28) наблюдалась тенденция к более выраженному неврологическому дефициту по шкале инвалидизации EDSS по сравнению с пациентами с нормальными (от 0 до 20 ЛЕ, n=30) и средними (от 20 до 800 ЛЕ, n=25) титрами НАТ (p>0,05). В группе пациентов с титрами НАТ от 20 до 800 ЛЕ частота обострений была несколько ниже, чем в группах больных с высоким и нормальным уровнем НАТ (p>0,05). Заключение. Тестирование НАТ может оказаться перспективным методом мониторинга терапии ИФН-β при рассеянном склерозе. У пациентов с высокими титрами НАТ была отмечена тенденция к повышению степени неврологического дефицита, но парадоксальные данные по высокой частоте обострений у пациентов с отсутствием НАТ требуют дальнейшего изучения.
Список литературы
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Almanac of Clinical Medicine. 2016; 44: 317-323
THE INFLUENCE OF NEUTRALIZING ANTIBODIES TO INTERFERON-BETA ON PROGRESSION OF MULTIPLE SCLEROSIS
https://doi.org/10.18786/2072-0505-2016-44-3-317-323Abstract
Background: Neutralizing antibodies (NAbs) affect the effectiveness of interferon therapy in patients with multiple sclerosis; however, this influence cannot be considered as unequivocal. NAbs formation is determined by several factors, such as frequency and duration of administration, interferon-β (IFN-β) formulation and the patient's genotype. It has been found that NAb titers vary over time. Aim: To assess the levels of NAbs to IFN-β in patients with multiple sclerosis and to investigate their relationship to disease progression. Materials and methods: We analyzed serum samples from 83 multiple sclerosis patients after a long-term IFN-β-1b treatment; NAbs detection reaction was performed by assessment of their cytopathic effect. Results: NAbs were found in 63.9% (53 of 83) of patients with duration of IFN-β-1b treatment of 33.3±17.6 months. All NAb-positive patients were treated with highdose IFN-β. Patients with titers>800 LU (n=28) demonstrated a trend towards more advanced neurologic deficit on the Expanded Disability Status Scale (EDSS), compared to the patients with normal NAbs titers (0 to 20 LU, n=30) and intermediate titers (20 to 800 LU, n=25) (p>0.05). The exacerbation rate in the group with NAbs titers from 20 to 800 LU was insignificantly lower than that in the group with NAbs>800 and in the NAb-negative patients (p>0.05). Conclusion: Testing for NAbs may be a promising method for monitoring of IFN-β therapy in multiple sclerosis. There was a trend towards more pronounced neurological deficit in patients with high NAbs titers, but paradoxical data on a high rate of exacerbations in NAb-negative patients requires further study.
References
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2. Bridel C, Lalive PH. Update on multiple sclerosis treatments. Swiss Med Wkly. 2014;144:w14012. doi: 10.4414/smw.2014.14012.
3. Farrell RA, Marta M, Gaeguta AJ, Souslova V, Giovannoni G, Creeke PI. Development of resistance to biologic therapies with reference to IFN-β. Rheumatology (Oxford). 2012;51(4):590–9. doi: 10.1093/rheumatology/ ker445.
4. Fox E, Green B, Markowitz C, Murray R, Goodman AD, Glenski SJ, Loupe P, Cogburn JN. The effect of scheduled antibody testing on treatment patterns in interferon-treated patients with multiple sclerosis. BMC Neurol. 2014;14:73. doi: 10.1186/1471-2377-14-73.
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10. Creeke PI, Farrell RA. Clinical testing for neutralizing antibodies to interferon-β in multiple sclerosis. Ther Adv Neurol Disord. 2013;6(1):3– 17. doi: 10.1177/1756285612469264.
11. Kappos L, Clanet M, Sandberg-Wollheim M, Radue EW, Hartung HP, Hohlfeld R, Xu J, Bennett D, Sandrock A, Goelz S; European Interferon Beta-1a IM Dose-Comparison Study Investigators. Neutralizing antibodies and efficacy of interferon beta-1a: a 4-year controlled study. Neurology. 2005;65(1):40–7. doi: 10.1212/01. wnl.0000171747.59767.5c.
12. Pachner AR, Warth JD, Pace A, Goelz S; INSIGHT investigators. Effect of neutralizing antibodies on biomarker responses to interferon beta: the INSIGHT study. Neurology. 2009;73(18):1493– 500. doi: 10.1212/WNL.0b013e3181bf98db.
13. Deisenhammer F. Neutralizing antibodies to interferon-beta and other immunological treatments for multiple sclerosis: prevalence and impact on outcomes. CNS Drugs. 2009;23(5):379–96. doi: 10.2165/00023210- 200923050-00003.
14. Noronha A. Neutralizing antibodies to interferon. Neurology. 2007;68(24 Suppl 4):S16–22. doi: 10.1212/01.wnl.0000277705.63813.84.
15. Hegen H, Schleiser M, Gneiss C, Di Pauli F, Ehling R, Kuenz B, Lutterotti A, Berger T, Deisenhammer F. Persistency of neutralizing antibodies depends on titer and interferon-beta preparation. Mult Scler. 2012;18(5):610–5. doi: 10.1177/1352458511426738.
16. van der Voort LF, Gilli F, Bertolotto A, Knol DL, Uitdehaag BM, Polman CH, Killestein J. Clinical effect of neutralizing antibodies to interferon beta that persist long after cessation of therapy for multiple sclerosis. Arch Neurol. 2010;67(4):402–7. doi: 10.1001/archneurol.2010.21.
17. Sørensen PS, Deisenhammer F, Duda P, Hohlfeld R, Myhr KM, Palace J, Polman C, Pozzilli C, Ross C; EFNS Task Force on Anti-IFN-beta Antibodies in Multiple Sclerosis. Guidelines on use of anti-IFN-beta antibody measurements in multiple sclerosis: report of an EFNS Task Force on IFN-beta antibodies in multiple sclerosis. Eur J Neurol. 2005;12(11):817–27. doi: 10.1111/j.1468-1331.2005.01386.x.
18. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292–302. doi: 10.1002/ ana.22366.
