Association of CD58 Polymorphism with Multiple Sclerosis and Response to Interferon ß Therapy in A Subset of Iranian Population

Objective: Multiple sclerosis (MS) is one of the leading neurodegenerative causes of physical disability world-wide. Genetic aberrations of autoimmunity pathway components have been demonstrated to significantly influence MS development. Cluster of Differentiation 58 (CD58) is pertained to a group of genes which had been assayed in several recent association studies. Given the significance of CD58 in modulation of T regulatory cells that control autoimmune responses, the present study was conducted to investigate the frequency of rs12044852 polymorphism and its effect on the outcome of interferon beta (IFN-β) therapy in a subset of Iranian MS patients. Materials and Methods: Two hundred MS patients and equal number of healthy controls were recruited to be genotyped in an experimental case-control based study through polymerase chain reaction using specific sequence primers (PCR-SSP). Relapsing remitting multiple sclerosis (RRMS) patients administered IFN-β therapy were followed up with clinical visits every three months up to two years. The mean of multiple sclerosis severity score (MSSS) and expanded disability status scale (EDSS) were measured to monitor the change in severity of MS in response to IFN-β therapy. Pearson’s Chi-square and analysis of variance (ANOVA) tests were the main statistical methods used in this study. Results: Strong association was found between the CC genotype and onset of MS (p=0.001, OR=2.22). However, there was no association between rs12044852 and various classifications and severity of MS. Pharmacogenetics-based analysis indicated that carriers of CC genotype had the highest MSSS score compared to others, implying a negative impact of rs12044852 on response to IFN-β t herapy. Conclusion: Taken together, our findings revealed the critical effect of rs12044852 polymorphism of CD58 on the progression of MS disease. This indicates that genotyping of MS patients may expedite achieving personalized medical management of MS patients

Comparison of Epstein Barr Virus Antibodies And Tcell Cytokines Production in Patients With Multiple Sclerosis and Healthy Individuals

Background:Multiple sclerosis(MS) is the most common autoimmune disease of central nervous system with destruction of myelin sheath mediated by auto reactive CD4+ T Lymphocytes. Because of the possible role of Epstein-Barr virus in etiology of MS and T cells immune response, the aim of this study was to evaluate anti-Epstein Barr virus antibodies as a marker of reactivity and production of TH1 and TH2 cytokines in MS patients and healthy individuals.   Methods: Blood samples were taken from 68 MS patients at different stages of diseases and 20 apparently healthy individuals and plasma levels of anti- EBV nuclear antigen-1 (EBNA-1) and viral capsid antigen (VCA) antibodies determined and concentrations of IFN- [1] , IL-12 and IL-4 in culture supernatants of PHA-activated peripheral blood mononuclear cells (PBMC) were measured by ELISA.   Results: The mean levels of anti EBNA-1 and VCAantibodies were significantly higher in patients compared to controls (p=0.04, p=0.001 respectively). Concentrations of IFN- [1] , IL-4 & IL-12 were also significantly higher in MS patients than healthy individuals (p=0.001, p=0.005, p=0.002, respectively). Significant correlation was found between anti EBNA-1 and VCAantibodies and IL-12 production (p =0.02, r=0.27& p=0.04, r=0.25, respectively); whereas no significant correlation was found between these antibodies and production of IFN- [1] or IL-4.   Conclusions: Due to elevated level of anti-EBV antibodies and T cell Cytokines in MS patients Rather than healthy individuals, Epstein Barr virus may play role in etiology of MS disease through activation of T cells immune response

Primary Angiitis of the Central Nervous System

Primary angiitis of the central nervous system (PACNS) is an idiopathic disorder (vasculitis) restricted to the central nervous system (CNS). It often presents with focal neurological deficits suggesting stroke or a combination of confusion and headache. We herein report three cases with various combinations of fever, partial seizure, encephalopathy, paresis, headache and ataxia. One of them was initially treated as herpes simplex meningoencephalitis, but further investigations revealed primary angiitis. Primary angiitis of the CNS has protean manifestations and should always be considered in patients suspicious to have CNS infection or stroke, particularly who does not respond to the routine treatments. Clinical data, exclusion of differential diagnoses and typical angiography seem to be enough to justify the diagnosis in the majority of cases

Detection of Duchenne/Becker Muscular Dystrophy Carriers in a Group of Iranian Families by Linkage Analysis

This study determines the value of linkage analysis using six RFLP markers for carrier detection and prenatal diagnosis in familial DMD/BMD cases and their family members for the first time in the Iranian population. We studied the dystrophin gene in 33 unrelated patients with clinical diagnosis of DMD or BMD. Subsequently, we determined the rate of heterozygosity for six intragenic RFLP markers in the mothers of patients with dystrophin gene deletions. Finally, we studied the efficiency of linkage analysis by using RFLP markers for carrier status detection of DMD/BMD. In 63.6% of the patients we found one or more deletions. The most common heterozygous RFLP marker with 57.1% heterozygosity was pERT87.15Taq1. More than 80% of mothers in two groups of familial or non-familial cases had at least two heterozygous markers. Family linkage analysis was informative in more than 80% of the cases, allowing for accurate carrier detection. We found that linkage analysis using these six RFLP markers for carrier detection and prenatal diagnosis is a rapid, easy, reliable, and inexpensive method, suitable for most routine diagnostic services. The heterozygosity frequency of these markers is high enough in the Iranian population to allow carrier detection and prenatal diagnosis of DMD/BMD in more than 80% of familial cases in Iran

A report of multiple sclerosis patients treated by CinnoVex™ in Iran

"n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Recent studies present a high prevalence of multiple sclerosis (MS) in Iran. Treatment with interferon is now the first choice in management of MS. CinnoVexTM (an interferon beta 1-a) is available in Iran, with achievement of the technology of producing beta interferon. The aim of the present study is to evaluate the efficacy and safety of CinnoVexTM in a national study named CINA study."n"nMethods: This study was conducted from 2007 to 2008 in cities of Tehran, Isfahan, Mashhad, Tabriz, and Shiraz. Patients with relapsing/remitting MS with 16-50 years of age and EDSS of <4 received CinnoVexTM (30µg/week, IM) after diagnosis by a neurologist. EDSS, drug side effects, and frequency of relapse were evaluated for one year in four 3-month visits."n"nResults: A total of 1050 patients entered the study. Complete data were collected from 627 (60%) patients. Mean age was 30.7±8.6 year and 514 (82%) were female. The most common onset presentations were sensory symptoms (44%). Changes of EDSS through the study showed a significant decrease in the last 3-month of evaluation (p<0.05). Drug side effects were observed in 47%, 50%, 61%, and 61.4% (p>0.05) and relapse was occurred in 13.4%, 15.7%, 16.9%, and 2.4% of the patients in the first, second, third, and forth evaluation visits (p=0.001), respectively."n"nConclusion: CinnoVexTM prevents progression and improves clinical course of MS. The conventional side effects of beta interferon therapy, however, are observed with CinnoVexTM