Association of CD58 polymorphism with multiple sclerosis and response to interferon beta therapy in a subset of Iranian population

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- beta] therapy in a subset of Iranian MS patients. 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- beta 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- beta therapy. Pearson's Chi-square and analysis of variance [ANOVA] tests were the main statistical methods used in this study. 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- beta t herapy. 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

Granulocyte Colony-Stimulating Factor for Amyotrophic Lateral Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study of Iranian Patients

BACKGROUND AND PURPOSE: The aim of this study was to determine the efficacy and tolerability of granulocyte colony-stimulating factor (G-CSF) in subjects with amyotrophic lateral sclerosis (ALS). METHODS: Forty subjects with ALS were randomly assigned to two groups, which received either subcutaneous G-CSF (5 microg/kg/q12h) or placebo for 5 days. The subjects were then followed up for 3 months using the ALS Functional Rating Scale-Revised (ALSFRS-R), manual muscle testing, ALS Assessment Questionnaire-40, and nerve conduction studies. CD34+/CD133+ cell count and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated at baseline. RESULTS: The rate of disease progression did not differ significantly between the two groups. The reduction in ALSFRS-R scores was greater in female subjects in the G-CSF group than in their counterparts in the placebo group. There was a trend toward a positive correlation between baseline CSF MCP-1 levels and the change in ALSFRS-R scores in both groups (Spearman's rho=0.370, p=0.070). CONCLUSIONS: With the protocol implemented in this study, G-CSF is not a promising option for the treatment of ALS. Furthermore, it may accelerate disease progression in females.

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