The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells.

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays critical roles in orchestrating of immune system, especially cytokine receptors and they can modulate the polarization of T helper cells. This pathway is regulated by an array of regulator proteins, including Suppressors of Cytokine Signaling (SOCS), Protein Inhibitors of Activated STATs (PIAS) and Protein Tyrosine Phosphatases (PTPs) determining the initiation, duration and termination of the signaling cascades. Dysregulation of the JAK-STAT pathway in T helper cells may result in various immune disorders. In this review, we represent how the JAK-STAT pathway is generally regulated and then in Th cell subsets in more detail. Finally, we introduce novel targeted strategies as promising therapeutic approaches in the treatment of immune disorders. Studies are ongoing for identifying the other regulators of the JAK-STAT pathway and designing innovative therapeutic strategies. Therefore, further investigation is needed.

Mycoplasma pneumonia seroposivity in Iranian patients with relapsing-remitting multipl sclerosis: a randomized case-control study.

OBJECTIVES: Environmental factors, such as different infections, have proposed to be involved in the pathogenesis of multiple sclerosis (MS). This study aimed to the evaluate mycoplasma pneumonia seropositivity, as a common cause of community-acquired pneumonia in patients with relapsing-remitting multiple sclerosis (RRMS). METHODOLOGY: Using ELISA method, IgM and IgG antibodies to Mycoplasma pneumoniae were determined in 130 patients with relapsing-remitting multiple sclerosis (85 Remitted and 45 Relapsed) and 50 sex- and age-matched controls. The groups were compared using Kruskal-Wallis test at the significant level of p < 0.05. RESULTS: The median [interquartile range] titer of IgG in remitted multiple sclerosis group was 65.3 [51.1-75.2] RU/ml versus 64 [52.6-71.4] RU/ml in relapsed group and 57.5 [29.2-74.3] RU/ml in control group (p = 0.442). There was not any significant difference between the groups base on median titer of IgM too (p = 0.446). The median [interquartile range] titer of Mycoplasma pneumoniae (MPn) IgG in women was 69.2 [56.4-77.4] RU/ml in remitted patients versus 63.85 [52.45-71.25] RU/ml in relapsed patients and 55.2 [29.17-72.75] RU/ml in controls (p = 0.022). Post hoc analysis demonstrated significant difference between remitted patients and controls (p = 0.002). There was not any significant difference between men in the groups (p = 0.7). CONCLUSIONS: Mycoplasma seroposivity in relapsing-remitting multiple sclerosis was not significantly different in various phases of activity of disease compare to controls; but in women, seroposivity of Mycoplasma antibodies were more than controls.

Chlamydia pneumoniae seropositivity in Iranian patients with multiple sclerosis: a pilot study.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. Genetic and environmental factors could not completely explain the pathogenesis of the disease. Among environmental factors, infectious agents are of more interest than other candidates, so Chlamydia pneumoniae (C. pneumoniae) may have a role in MS development or progression. This study aimed to evaluate C. pneumoniae seropositivity in MS patients. MATERIAL AND METHODS: Serum samples obtained from a cohort of 85 patients with MS and from 50 age- and sex-matched controls were assessed for the presence of antibodies. IgM and IgG concentration for C. pneumoniae were determined with enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean age was 33.8 (9.96) years in the MS group and 33.9 (10.7) years in controls. Female/male ratio was 3.5 : 1 in the MS group; 69 patients (81%) had relapsing-remitting course (RRMS) and 16 patients (19%) had secondary progressive course (SPMS). The median concentration of C. pneumoniae IgM in the MS group was 0.5 RU/mL (0.25-1) versus 0.5 RU/mL (0.3-0.8) in the control group (p = 0.66); likewise, the median concentration of C. pneumoniae IgG in MS patients was 57.3 RU/mL (17.05-95.1) compared with 56.15 RU/mL (6.85-102.5) in the control group (p = 0.85). Regarding the clinical course, C. pneumoniae IgG was 55.1 RU/mL (20.7-88.6) in RRMS and 59.1 RU/mL (5.35-112) in SPMS (p = 0.8). CONCLUSION: No association was observed between MS and C. pneumoniae in Iranian MS patients.

Serum uric acid level in patients with relapsing-remitting multiple sclerosis.

Uric acid (UA) is a hydrophilic antioxidant product associated with multiple sclerosis (MS). We conducted a randomized case-control study to evaluate the serum level of UA in different phases of MS in comparison with levels in a healthy control population. Serum UA was checked in 130 patients with relapsing-remitting MS (85 patients in remitting and 45 patients in relapsing phase) and 50 age-matched controls using a quantitative enzyme-linked immunosorbent assay (ELISA). The mean concentrations of UA in serum was 6.41(±3.18)mg/dL in patients with remitting MS, 4.76(±1.66)mg/dL in patients with relapsing MS and 6.33(±2.94)mg/dL in controls. There was a significant difference between mean UA concentration in relapsing MS and remitting MS (p<0.001), and between patients with relapsing MS and controls (p=0.002); however, the difference between levels for patients in the remitting phase of MS and the control group was not significant (p=0.87). It seems probable that UA has a role in the prevention of disease activity in MS.

Investigation of tRNA and ATPase 6/8 gene mutations in Iranian ataxia telangiectasia patients.

INTRODUCTION: Ataxia telangiectasia (AT) is a rare human neurodegenerative autosomal recessive multisystem disease. AT is the result of mutations in the AT-mutated (ATM) gene. ATM protein is required for radiation-induced apoptosis and acts before mitochondrial collapse. The tRNA genes are considered one of the hot spots for mutations causing mitochondrial disorders. Due to the important role of ATM in apoptosis and its effect on the cell cycle it might be possible that it has a central role in mtDNA mutations. On the other hand, the tRNA(Lys/Leu) gene and also ATPase6 and ATPase8 genes are important for many mitochondrial diseases and many causative mutations have been reported from these genes. MATERIAL AND METHODS: In the present research, we performed mutation screening for these genes in 20 patients who were diagnosed with ataxia telangiectasia by a PCR sequencing method. RESULTS: The results showed a significant level of mtDNA variations in AT patients. Among 20 patients in this study, 12 patients (60%) were detected with point mutations, among which 8 mutations (40%) belonged to the MT-ATP6 gene. There was probably a second effect of mtDNA mutations in AT disease and mtDNA plays a main role in establishment of AT. CONCLUSIONS: MtDNA mutations might be responsible for the decline of mitochondrial function in AT patients. Mitochondrial investigation can help to understand the mechanism of damage in AT disease.