TIM-3 genetic variants and risk of Behçet disease in the Iranian population.

BACKGROUND: Behçet disease is a prototypical systemic autoimmune disease, caused by a complex interplay between environmental and genetic factors. The transmembrane immunoglobulin and mucin domain-3 (TIM-3) is a distinct member of the TIM family that is preferentially expressed on Th1 cells and plays a role in Th1-mediated autoimmune or inflammatory diseases, such as Behçet disease. OBJECTIVE: The aim of this study was to test the potential association between TIM-3 gene polymorphisms and Behçet disease. METHODS: Two single-nucleotide polymorphisms of TIM-3 (rs9313439 and rs10515746) were genotyped in 212 patients with Behçet disease and 200 healthy controls. Typing of the polymorphisms was performed using multiplex PCR amplification. RESULTS: There were no significant differences in allele and genotype frequencies between the Behçet disease patients and controls who were successfully genotyped. Similar results were also found after stratification by gender, age, or clinical features. STUDY LIMITATIONS: Lack of studies on various racial or ethnic groups and small sample size. CONCLUSION: This study failed to demonstrate any association between the tested TIM-3 polymorphisms and Behçet disease.

Enhanced Th17 Responses in Patients with Autoimmune Hepatitis.

BACKGROUND T cells are major players in chronic inflammatory diseases such as autoimmune hepatitis (AIH). However, it is not clear which subset of T cells participates in the pathophysiology of the disease. The aim of this study was to assess the expression profile of signature transcription factor and cytokines of T helper 17 (Th17) cells in patients with AIH. METHODS A total of 24 patients with AIH and 24 normal subjects were recruited in the study. Comparison of gene expression patterns between the patients and normal subjects was done by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS The results showed that retinoic acid receptor-related orphan receptors gamma (RORÉ£t), interleukin-17A (IL-17A), and interleukin-22 (IL-22) mRNA expression were increased greatly in the patients group compared with the normal controls group (p < 0.05). CONCLUSION Deregulated production of Th17-related molecules may be associated with the pathogenesis of AIH.

TIM-3 genetic variants and risk of Behçet disease in the Iranian population

Abstract: Background: Behçet disease is a prototypical systemic autoimmune disease, caused by a complex interplay between environmental and genetic factors. The transmembrane immunoglobulin and mucin domain-3 (TIM-3) is a distinct member of the TIM family that is preferentially expressed on Th1 cells and plays a role in Th1-mediated autoimmune or inflammatory diseases, such as Behçet disease. Objective: The aim of this study was to test the potential association between TIM-3 gene polymorphisms and Behçet disease. Methods: Two single-nucleotide polymorphisms of TIM-3 (rs9313439 and rs10515746) were genotyped in 212 patients with Behçet disease and 200 healthy controls. Typing of the polymorphisms was performed using multiplex PCR amplification. Results: There were no significant differences in allele and genotype frequencies between the Behçet disease patients and controls who were successfully genotyped. Similar results were also found after stratification by gender, age, or clinical features. Study limitations: Lack of studies on various racial or ethnic groups and small sample size. Conclusion: This study failed to demonstrate any association between the tested TIM-3 polymorphisms and Behçet disease.

Increased Expression of Aryl Hydrocarbon Receptor in Peripheral Blood Mononuclear Cells of Patients with Autoimmune Hepatitis.

BACKGROUND Previous studies have indicated an elevated level of serum Interleukin (IL)-22 in patients with autoimmune hepatitis (AIH). However, there are no experimental data on the master transcription factor (aryl hydrocarbon receptor) that plays an important role in the development of T helper type 22 (Th22) cells as major producers of IL-22. The aim of the present study was to examine the expression of aryl hydrocarbon receptor in patients with AIH and in normal controls. METHODS Levels of mRNA transcripts were measured in the peripheral blood mononuclear cells of 18 patients with AIH and compared with 18 normal controls by a quantitative real-time polymerase chain reaction. RESULTS mRNA expression of aryl hydrocarbon receptor was significantly higher in patients with AIH compared with the healthy control group (P = 0.006). CONCLUSION Th22 cells may play an important role in the pathogenesis of AIH.

Imbalance of Peripheral Blood T Helper Type 17 Responses in Patients with Vitiligo.

There is growing evidence to suggest that Th cells play pivotal roles in a variety of chronic inflammatory diseases, including vitiligo. However, the exact role of different subsets of Th cells in the pathogenesis of vitiligo is still a question. The purpose of present study was to determine the mRNA expression level of Th17 master transcription factor retinoic acid receptor-related orphan receptors gamma (RORÉ£t) and cytokine mRNA and protein expression profiles of Th17 cells. 22 patients with vitiligo and 22 normal subjects were enrolled in the study. Gene expression profiles of freshly isolated peripheral blood mononuclear cells (PBMCs) were determined by quantitative real-time reverse transcriptase PCR (qRT-PCR). Plasma concentrations of IL-17A and IL-22 were also assayed using ELISA kits. The results showed that RORÉ£t, IL-17A and IL-22 mRNA expression were increased in patients remarkably compared to healthy controls (p<0.05). Furthermore, plasma IL-17A and IL-22 levels were also higher in vitiligo patients versus controls (p<0.001). These data suggest that a deregulated Th17 adaptive immune response may contribute to the pathogenesis of vitiligo.

Role of Th1/Th2 cells and related cytokines in autoimmune hepatitis.

BACKGROUND/AIMS: Dysregulation of T cell response is thought to play an important role in the immunopathogenesis of autoimmune hepatitis. However, no consensus has yet been reached regarding the implications of a distinct T cell subset in the pathogenesis of this progressive liver disease. Therefore, T-bet and GATA-3 expression was examined in patients with autoimmune hepatitis (AIH) and in healthy controls. Moreover, the profile of Th1 (IFN-γ) and Th2 (IL-4) cytokine gene expression was analyzed. MATERIALS AND METHODS: Levels of mRNA transcripts were measured in peripheral blood mononuclear cells (PBMCs) using a two-step reverse transcription quantitative real-time polymerase chain reaction with SYBR Green. RESULTS: T-bet and IFN-γ mRNA expression was significantly higher in AIH patients compared to healthy controls (p<0.05), whereas no differences were observed for either GATA-3 or IL-4 mRNA expression (p>0.05). CONCLUSION: Alterations in the Th1/Th2 cell balance may be responsible for both disease progression and the resulting complications.

Association of Two Polymorphic Codons in P53 and ABCC1 Promoter with Prostate Cancer.

BACKGROUND: In prostate cancer, mutated p53 alleles typically contain missense single-base substitution in codon 72 that resides within exons 5-8. Stable p53 proteins in tumor cell nuclei have been associated with malignancy. A role of p53 is the regulation of drug transporters like ABCC1 (MRP1) by an effect on promoter region. OBJECTIVES: The objective of this study was to identify association of mutations of p53 at codon 72 and 282 and promoter region of ABCC1 with increased risks of prostate cancer. MATERIALS AND METHODS: Formalin fixed, paraffin-embedded malignant tissues of 45 patients and 45 control samples were evaluated. PCR-RFLP using BstUI for codon 72 and HpaII restriction enzyme for codon 282 p53 gene, and G-1666A promoter region of ABCC1 gene was performed. To assess the frequency of these mutations and to detect new mutations in cancerous samples, PCR-SSCP analysis was performed. RESULTS: The frequencies of CC, GC and GG genotypes of codon 72 of p53 were 33.33%, 46.67% and 20.00% in patients with cancer and 15.56%, 48.89% and 35.55% in controls, respectively. The relative allele frequencies of ABCC1 promoter polymorphism were 60.00% A and 40.00% G in patients as opposed to 37.78% for A and 62.22% for G in controls. Genotypic frequencies of p53 codon 72 and G1666A of ABCC1 in patients vs. Controls were statistically significant(p<0.05). The study of these samples with PCR-SSCP displayed some new banding patterns. CONCLUSIONS: The present findings suggest that CC homozygosity in codon 72 of p53 gene and AA genotype in G-1666A of ABCC1 gene may play a role in combination in prostate cancer and increased susceptibility for this malignancy in the Iranian Kurdish population.