IL-1, IL-1R and TNFalpha gene polymorphisms in Iranian patients with multiple sclerosis

Different research groups have extensively studied the associations of cytokine gene polymorphisms in different diseases. The role of cytokines gene polymorphisms in multiple sclerosis [MS], as a chronic Immune-mediated neurodegenerative disease, has been previously reported in the various populations. For determining pro-inflammatory cytokine gene polymorphisms, 100 relapsing remitting multiple sclerosis [RRMS] Iranian patients and 140 normal individuals as control enrolled in this study. DNA of each sample was extracted by a modified salting out method. Cytokine single gene nucleotide polymorphisms including IL-1alpha -889, IL-1beta [-511 and +3962], IL-1R pst1 1970, IL-1RA mspal 11100, and TNF-alpha [-308 and -238] were determined by using the PCR-SSP method. The results of our data indicate the decrease in frequency of IL-1alpha TC-889 genotype [p=0.002], IL-1beta TC +3962 genotype [p=0.004], IL-1R T pst1 1970 allele [p= 0.0001], IL-1 RA TC Mspa1 11100 genotype [p=0.009], TNF-alpha A-308 allele [p=0.0002] and AG genotype [p=0.00001] in the patients group versus normal subjects. On the other hand the frequency of IL-1alpha TT -889 genotype [p=0.028], IL-1R C pst1 1970 allele [p=0.0001] and CC genotype [p=0.00006], TNFalpha G -308 allele [p=0.0002] and GG genotype [p=0.000001] decreased significantly in the patients versus normal subjects. These results suggest that polymorphic variations of these pro-inflammatory cytokines may play an important role in susceptibility of Iranian multiple sclerosis patients

Does mesenchymal stem cell therapy help multiple sclerosis patients? report of a pilot study

Mesenchymal stem cells [MSCs] with their potential to differentiate into mesodermal and non-mesodermal lineages have several immunomodulatory characteristics. These properties make them promising tools in cell and gene therapy. To evaluate the potential therapeutic applications of autologous MSC in improving clinical manifestations of MS patients. Ten patients were included in this pilot study. All had progressive disease that had not responded to disease modifying agents including Mitoxantrone. Their Expanded Disability Status Scale [EDSS] score ranged from 3.5 to 6. Patients were injected intrathecally with culture expanded MSCs. They were followed with monthly neurological assessment and a MRI scan at the end of the first year. During 13 to 26 months of follow up [mean: 19 months], the EDSS of one patient improved from 5 to 2.5 score. Four patients showed no change in EDSS. Five patients' EDSS increased from 0.5 to 2.5. In the functional system assessment, six patients showed some degree of improvement in their sensory, pyramidal, and cerebellar functions. One showed no difference in clinical assessment and three deteriorated. The result of MRI assessment after 12 months was as following: seven patients with no difference, two showed an extra plaque, and one patient showed decrease in the number of plaques. This preliminary report emphasizes on the feasibility of autologous MSC for treatment of MS patients. However, in order to draw a definitive conclusion a larger sample size is required

Interferon-gamma gene polymorphism in Iranian patients with multiple sclerosis

Interferon- gamma [IFN- gamma] is an important immune regulator and inflammatory cytokine which is implicated in the pathogenesis of multiple sclerosis [MS]. A single nucleotide polymorphism, T to A, at position +874 in the first intron has previously been shown. This polymorphism is associated with IFN- gamma production level. To study the effect of this polymorphism on susceptibility to multiple sclerosis, we screened genomic DNA samples from clinically definite MS patients and their unaffected first-degree relatives as controls, using sequence-specific primers [PCR-SSP]. The results indicated that MS patients showed a lower TT [21.2% vs. 30.3%] and higher AA [21.2% vs. 12.1%] genotypes compared to controls, although there were statistically no differences in the IFN- gamma genotype distribution between these two groups. Thus, our data indicate that there is no association between IFN- gamma +874 polymorphism and MS susceptibility or severity of the disease