In silico perspectives on the prediction of the PLP's epitopes involved in multiple sclerosis

Background: Multiple sclerosis [MS] is the most common autoimmune disease of the central nervous system [CNS]. The main cause of the MS is yet to be revealed, but the most probable theory is based on the molecular mimicry that concludes some infections in the activation of T cells against brain auto-antigens that initiate the disease cascade

Objectives: The Purpose of this research is the prediction of the auto-antigen potency of the myelin proteolipid protein [PLP] in multiple sclerosis

Materials and Methods: As there wasn't any tertiary structure of PLP available in the Protein Data Bank [PDB] and in order to characterize the structural properties of the protein, we modeled this protein using prediction servers. Meta prediction method, as a new perspective in silico, was performed to find PLPs epitopes. For this purpose, several T cell epitope prediction web servers were used to predict PLPs epitopes against Human Leukocyte Antigens [HLA]. The overlap regions, as were predicted by most web servers were selected as immunogenic epitopes and were subjected to the BLASTP against microorganisms

Results: Three common regions, AA[58-74], AA[161-177], and AA[238-254] were detected as immunodominant regions through meta-prediction. Investigating peptides with more than 50% similarity to that of candidate epitope AA[58-74] in bacteria showed a similar peptide in bacteria [mainly consistent with that of clostridium and mycobacterium] and spike protein of Alphacoronavirus 1, Canine coronavirus, and Feline coronavirus. These results suggest that cross reaction of the immune system to PLP may have originated from a bacteria or viral infection, and therefore molecular mimicry might have an important role in the progression of MS

Conclusions: Through reliable and accurate prediction of the consensus epitopes, it is not necessary to synthesize all PLP fragments and examine their immunogenicity experimentally [in vitro]. In this study, the best encephalitogenic antigens were predicted based on bioinformatics tools that may provide reliable results for researches in a shorter time and at a lower cost

Expression and prognostic significance of Bcl-2 and Bax in the progression and clinical outcome of transitional bladder cell carcinoma

To evaluate the mRNA expression ratio of Bcl-2/Bax both in normal and tumoral bladder tissues of patients with transitional cell carcinoma [TCC] of bladder and investigate potential correlation between this expression ratio and clinical outcome. In this experimental study, we used real time-PCR to investigate the expression of Bcl-2 and Bax both in normal and tumoral bladder tissues. The Bcl-2/Bax expression ratio was determined in tumoral bladder tissues of patients with transitional cell carcinoma of the bladder [n=40] and correlation between expression ratios and the emergence of early relapses in a follow-up of 14-30 months was examined. Relapse-free time in 14/31 patients [45.16%] with Bcl-2/Bax>1 was shorter than 9 months [range of 2-9 months] with 5.7 months average median while 17/31 patients [54.84%] with Bcl-2/Bax<1 are currently relapse-free [14-30 months]. Bcl-2 and Bax expression levels were not solely correlated with clinical outcome and progression of carcinogenesis. The mRNA expression ratio of Bcl-2/Bax in tumoral bladder tissues may serve as a significant prognostic indicator in predicting the clinical outcome in low grade non-invasive bladder cancer

Contribution of GJB2 mutations and Four common DFNB loci in autosomal recessive non-syndromic hearing impairment in Markazi and Qom provinces of Iran

This study aimed to investigate the contribution of four common DFNB ["DFN" for deafness and "B" for autosomal resessive locus] loci and GJB2 gene mutations [exon 2] in hearing impairment in individuals living in Markazi and Qom provinces of Iran. Forty consanguineous Iranian families with at least three affected individuals in family or pedigree who suffer from an autosomal recessive non-syndromic congenital hearing impairment were the subjects of this study. Blood samples were taken from both hearing and non-hearing individuals, DNA was extracted and amplified by using specific primers for the coding region of GJB2 gene [exon 2]. The PCR product of GJB2 gene was then sequenced. Also short tandem repeat [STR] markers amplified by using specific primers for loci DFNB2, DFNB3, DFNB4 and DFNB21. At least 2 microsatellite markers [STR] for each DFNB locus exceeding to 4-6 markers for the linked families were used. The amplified markers were analyzed by conventional Polyacrylamide Gel Electrophoresis followed by silver staining. Six families were homozygous or compound heterozygous for GJB2 mutations and were excluded from further studies. Linkage analysis was carried out for the remaining 34 families by genotyping the flanked STR markers of DFNB2, DFNB3, DFNB4 and DFNB21 loci. Six families showed linkage; including one family to DFNB2, two families to DFNB3 and three families to DFNB4 locus while no family showed linkage to DFNB21 locus. Undoubtedly, the best understanding of the genetic basis of hearing loss in Iranian population will be achieved by performing similar experiments in other provinces and also by analyzing more loci

Mutation analysis of connexin 26 gene and del[GJB6-D13S1830] in patients with hereditary deafness from two provinces in Iran

Mutations in the connexin 26 [Cx26] gene at the DFNB1 locus on chromosome 13q12 are associated with autosomal recessive non-syndromic hearing loss [ARNSHL]. There are many known mutations in this gene that cause hearing loss. A single frameshift, at position 35 [35delG] accounts for 50% of mutations in the Caucasian population with carrier frequencies of 1.5-2.5%. In this study we investigated the prevalence of Cx26 gene mutations by directly sequencing the coding exon of this gene belonging to ARNSHL individuals from 53 families in Qom and Markazi provinces of Iran. Seven different Cx26 variants were identified. Five Cx26 mutations including 35delG, 233delC, 176del16, W24X, L90P were found in 10 of 53 families [18.87%]. One polymorphism V153I was also found. One variant A171T with unknown effects was also detected. Six of the 53 families were observed to have GJB2 mutations in both alleles [11.32%]. The most common mutation was 35delG. Three out of 10 families [30%] with GJB2 variants contained 35delG mutation in both alleles and the frequency of 35delG allele was 0.50 among 10 out of 53 families. Also screening for the 342-kb GJB6 deletion mutant did not reveal any large deletion among families studied. Thus, in the two provinces, contribution of GJB2 [Gap Junction Protein Beta 2] mutations to familial deafness appears to be less significant. This necessitates further assessment of the other known genes regions as well as a search for new genetic factors in hereditary deafness in the Iranian population