Razi Journal of Medical Sciences

fa بررسی میزان تولید آنتی‌بادی بر علیه داروی اینترفرون بتا در بیماران مبتلا به مولتیپل اسکلروزیس Evaluation of antibody production against interferon-beta in Multiple Sclerosis patients ایمنی‌شناسی Immunology پژوهشي Research <div style="text-align: justify;">زمینه و هدف: مولتیپل اسکلروزیس (MS) یک بیماری خود ایمنی تخریب کننده غلاف میلین تشکیل دهنده اکسون در نورون&rlm;های سیستم دستگاه عصبی مرکزی است که به طور معمول در افراد جوان ایجاد میشود. اینترفرون بتا IFN-β)) از اولین داروها با اثرات سودمند برای بیماری اماس است. اینترفرون ها (IFN) سیتوکین هایی هستند که دارای طیف گسترده ای از خواص ضد التهابی هستند. هدف اصلی این مطالعه، اندازهگیری آنتیبادی ضد اینترفرون بتا (CinnoVex) در سرم بیمارانی است که این دارو را مصرف میکنند. روش کار: نمونههای سرم ٢٦ فرد سالم و ٥٢ بیمار مبتلا به مولتیپل اسکلروزیس تحت درمان با اینترفرون بتا (٢٦ بیمار از هر گروه) برای سنجش حضور آنتیبادی بررسی شد. سرم این گروهها با روش الایزا مورد ارزیابی قرار گرفت و نتایج به دست آمده بصورت جداگانه مورد بررسی آماری قرار گرفت. یافته ها: بر اساس نتایج به دست آمده از ٢٦ بیمار مبتلا به مولتیپل اسکلروزیس که اینترفرون بتا دریافت کردند و به درمان پاسخ مثبت دادند، ٤ بیمار (16%) دارای آنتیبادی علیه اینترفرون بتا بودند، اما در 26 بیمار غیر پاسخ دهنده به اینترفرون بتا ، ٩ بیمار (35%) مثبت بودند. نتیجه گیری: در این پژوهش ملاحظه شد که درصد آنتیبادی ضد اینترفرون بتا در بیماران گروه دوم بیشتر از بیماران گروه اول است. بنابراین میتوان نتیجهگرفت که یکی از مهمترین عواملی که باعث میشود بیمار به داروی اینترفرون بتا پاسخ ندهد، تشکیل آنتیبادی ضد این دارو در سرم بیمار است که میتواند کارایی بالینی و فعالیت زیستی آن را کاهش دهد.  </div> <div style="text-align: justify;">Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system affecting young adults. MS attacks the myelinated axons in the CNS, destroying the myelin and the axons to varying degrees. The course of MS is highly varied and unpredictable. In most patients, the disease is characterized initially by episodes of reversible neurological deficits, which is often followed by progressive neurological deterioration over time. Twice as many women are affected as men. The disease is diagnosed on the basis of clinical findings and supporting evidence from ancillary tests, such as magnetic resonance imaging (MRI) of the brain and examination of the cerebrospinal fluid (CSF). MS typically present in adults 20 to 45 years of age; occasionally, it present in childhood or late middle age. The cause is unknown, but it appears to involve a combination of genetic susceptibility and a nongenetic trigger, such as a virus, metabolism, or environmental factors, that together result in a self-sustaining autoimmune disorder that leads to recurrent immune attacks on the CNS. Neurologists agree that patients may be grouped into four major categories based on the course of disease: Relapsing–remitting, Secondary progressive, Primary progressive and Progressive-relapsing. RRMS – the most common disease course – is characterized by clearly defined attacks of new or increasing neurologic symptoms. These attacks – also called relapses or exacerbations are followed by periods of partial or complete recovery (remissions). During remissions, all symptoms may disappear, or some symptoms may continue and become permanent. However, there is no apparent progression of the disease during the periods of remission. RRMS can be further characterized as either active (with relapses and/or evidence of new MRI activity over a specified period of time) or not active, as well as worsening (a confirmed increase in disability following a relapse) or not worsening. Approximately 85 percent of people with MS are initially diagnosed with RRMS. Interferon-beta (IFN-β) medications are commonly used as first-line therapy in multiple sclerosis. Interferons (IFNs) are naturally occurring cytokines possessing a wide range of anti-inflammatory properties. Recombinant forms of IFNβ are widely used as first-line treatment in relapsing forms of MS. The mechanism of action of IFNβ is complex, involving effects at multiple levels of cellular function. IFNβ appears to directly increase expression and concentration of anti-inflammatory agents while downregulating the expression of proinflammatory cytokines. Antibodies can develop during interferon-beta treatment and reduce or abrogate normal biologic and treatment effects. Anti-IFN-β antibodies can reduce both bioactivity and clinical efficacy of IFN-β. Binding antibodies (BAbs) are antibodies that bind to the drug but do not necessarily inhibit its biological action. BAbs may be detected within the first month of therapy. The rate at which they appear is dependent on the type of IFNβ used. Although BAbs do not necessarily inhibit the biological action of IFNβ, as therapy is continued, maturation of the antibody body response may result in the production of high-affinity neutralizing antibodies (NAbs). NAbs are a subset of BAbs which prevent the binding of the IFNβ to its receptor on the surface of cells. When BAbs are detectable it is likely that NAbs are also present, however their concentration and affinity generally increase as the response matures. Enzyme-linked Immunosorbent Assay (ELISA) can potentially be used to characterize the composition of the anti-IFN-beta antibody response. Currently, CinnoVex, a biosimilar product to Avonex produced by CinnaGen Company, Iran, is used to treat MS patients in Iran. The objective of this study was to measure serum anti-interferon antibodies (CinnoVex) in patients with MS and compare it between two groups of patients. The first group is patients with MS that received interferon-beta and responded to it. The second group was patients with MS that received interferon-beta and did not respond to it. Methods: An Indirect ELISA test was used for the measurement of anti-IFN-β antibodies. Sera were studied for anti-IFN-β antibodies from 26 healthy individuals and 52 MS patients (26 patients from each group) treated with Interferon-beta and the obtained results were analyzed statistically. Results: Patients were considered positive for Anti-IFN-β antibodies, if they had a positive sample with an optical density of more than 0.085. Anti-IFN-β antibodies were found in 4(14%) of MS patients treated with Interferon-beta and responded to it, but in 9 (35%) of MS patients treated with Interferon-beta and did not respond to it. Conclusion: In this study, we found that the percentage of anti-IFN-β antibodies in the second group was higher than in the first group, so we can conclude that one of the most important factors that caused the patients not to respond to interferon-beta, formation of anti-drug antibodies in the serum that can reduce clinical efficacy and bioavailability of drug.  </div> مولتیپل اسکلروزیس, اینترفرون بتا, آﻧﺘﯽ‌ﺑﺎدی‌ها, آنتی‌بادی‌های اتصالی, آنتی‌بادی‌های خنثی کننده, الایزا Multiple sclerosis, Interferon-beta, Antibodies, Binding Antibodies, Neutralizing Antibodies, Enzyme-linked Immunosorbent Assay 28 38 http://rjms.iums.ac.ir/browse.php?a_code=A-10-5151-1&slc_lang=fa&sid=1 Mahmoud Esraa Baghdadi محمود اسراء بغدادی mahmoudbaghdadi1987@gmail.com 3900319475328460053475 3900319475328460053475 No University of Isfahan دانشگاه اصفهان Omid mirmosayyeb امید میرمسیب omid.mirmosayyeb@gmail.com 3900319475328460053476 3900319475328460053476 No Isfahan University of Medical Sciences دانشگاه علوم پزشکی اصفهان Vahid Shaygannejad وحید شایگان نژاد shaygannejad@med.mui.ac.ir 3900319475328460053477 3900319475328460053477 No Isfahan University of Medical Sciences دانشگاه علوم پزشکی اصفهان Hamid Zarkesh Esfahani حمید زرکش اصفهانی s.h.zarkesh@sheffield.ac.uk 3900319475328460053478 3900319475328460053478 Yes University of Isfahan گروه زیست‌شناسی سلولی مولکولی و میکروبیولوژی، دانشکده علوم و فناوری‌های زیستی، دانشگاه اصفهان، اصفهان، ایران Narjes Ramezanipour نرجس رمضانی پور N.Ramezanipour@yahoo.com 3900319475328460053479 3900319475328460053479 No University of Isfahan دانشگاه اصفهان Rahman Emamzadeh رحمان امام زاده sci_rahman@yahoo.com 3900319475328460053480 3900319475328460053480 No University of Isfahan دانشگاه اصفهان