ABSTRACT
Abstract Background: Although not fully understood, oxidative stress has been implicated in the pathogenesis of different autoimmune diseases such as systemic sclerosis. Accumulating evidence indicates that oxidative stress can induce mitochondrial DNA (mtDNA) damage and variations in mtDNA copy number (mtDNAcn). Objective: The aim of this study was to explore mtDNAcn and oxidative DNA damage byproducts in peripheral blood of patients with systemic sclerosis and healthy controls. Methods: Forty six patients with systemic sclerosis and forty nine healthy subjects were studied. Quantitative real-time PCR used to measure the relative mtDNAcn and the oxidative damage (oxidized purines) of each sample. Results: The mean mtDNAcn was lower in patients with systemic sclerosis than in healthy controls whereas the degree of mtDNA damage was significantly higher in cases as compared to controls. Moreover, there was a negative correlation between mtDNAcn and oxidative DNA damage. Study limitations: The lack of simultaneous analysis and quantification of DNA oxidative damage markers in serum or urine of patients with systemic sclerosis and healthy controls. Conclusion: These data suggest that alteration in mtDNAcn and increased oxidative DNA damage may be involved in the pathogenesis of systemic sclerosis.
Subject(s)
Humans , Male , Female , Adult , Scleroderma, Systemic/genetics , Scleroderma, Systemic/blood , DNA Damage , DNA, Mitochondrial/genetics , DNA, Mitochondrial/blood , Oxidative Stress/genetics , DNA Copy Number Variations , Reference Values , Case-Control Studies , Reactive Oxygen Species/blood , Statistics, Nonparametric , Electrophoresis, Agar Gel , Real-Time Polymerase Chain Reaction , Middle AgedABSTRACT
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.
Subject(s)
Humans , Male , Female , Adult , Behcet Syndrome/genetics , Polymorphism, Single Nucleotide , Hepatitis A Virus Cellular Receptor 2/genetics , Case-Control Studies , Logistic Models , Risk Factors , Risk Assessment , Alleles , Genetic Association Studies , Multiplex Polymerase Chain Reaction , Gene Frequency , IranABSTRACT
Abstract: IL-22 has been implicated in the pathogenesis of vitiligo. However, the role of aryl hydrocarbon receptor transcription factor that acts as a master regulator of IL-22-producing Th22 cells is not fully understood. The goal of this study was to investigate the expression pattern of aryl hydrocarbon receptor in peripheral blood mononuclear cells of patients with vitiligo and in normal controls. Transcript levels were determined by a reverse transcription quantitative real-time polymerase chain reaction. Aryl hydrocarbon receptor mRNA expression was drastically increased in patients with vitiligo compared to healthy controls (P = 0.000). Th22 cells may contribute to abnormal immune responses underlying vitiligo.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Young Adult , Vitiligo/genetics , Up-Regulation/genetics , Receptors, Aryl Hydrocarbon/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , RNA, Messenger/genetics , Case-Control Studies , Gene Expression , Interleukins/analysis , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Abstract: Background: Psoriasis is a chronic inflammatory disorder, characterized by increased keratinocyte proliferation due to abnormal differentiation of basal keratinocytes. The etiology of the disease is unclear, and according to the survey results, it is hypothesized that a combination of genetic and environmental factors prompts an abnormal immune response in patients with psoriasis. CD4+ Th cells play a multifaceted role in both immune defense and pathogenesis of certain diseases such as psoriasis. Nonetheless, the exact contribution of different subpopulations of Th cells in psoriasis is still not clear. Objective: The aim of present study was to determine the mRNA expression level of RORC as potential inducer of Th17 cell differentiation and expression pattern of Th17-signature cytokines (IL-17A and IL-22). Methods: Twenty patients with psoriasis and twenty-one healthy subjects were included in the study. Peripheral blood mononuclear cells (PBMCs) were separated and expression of three genes were determined by quantitative real-time reverse transcriptase PCR (qRT-PCR). Plasma levels of IL-17 and IL-22 were also evaluated by ELISA. Results: RORC, IL-17A and IL-22 gene expression was significantly higher in patients with psoriasis compared with healthy controls (P<0.05). In addition, a marked increase in plasma IL-17A and IL-22 levels was observed in patient group compared to controls (P<0.001). Study limitations: small number of patients. Conclusion: These data suggest that Th17 response may contribute to the pathogenesis of psoriasis.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Psoriasis/metabolism , Keratinocytes/physiology , Nuclear Receptor Subfamily 1, Group F, Member 3/physiology , Th17 Cells/metabolism , Psoriasis/etiology , Severity of Illness Index , RNA, Messenger/metabolism , Case-Control Studies , Gene Expression , Keratinocytes/cytology , Cell Differentiation , Interleukins/blood , Interleukin-17/blood , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Th17 Cells/immunologyABSTRACT
Context: Recent investigations into the pathogenesis of sepsis reveal an important role for apoptosis. The present study was designed in order to assess the peripheral blood mononuclear cells' (PBMCs) apoptosis and the plasma levels of molecules associated with apoptosis belonging to tumor necrosis factor-alpha (TNF-α)/tumor necrosis factor type-1 receptor (TNFR I) pathway in patients with sepsis. Patients and Methods: Twenty-two patients with sepsis and 20 healthy subjects were included in the study. The percentage of PBMCs' apoptosis was examined using annexin-V at the time of blood draws (0 time). PBMCs were incubated for 24 hour at 37°C in medium (spontaneous apoptosis) and in the presence of TNF-α. After incubation, the percentage of apoptotic cells was counted. Plasma levels of TNF-α and soluble TNFR I (sTNFR I) were also measured by enzyme linked immunosorbent assay (ELISA). Results: PBMCs of patients showed a higher proportion of apoptotic cells than PBMCs of controls at 0 time. After 24 hour incubation, spontaneous apoptosis of PBMCs was nearly as high as that of TNF induced apoptosis. Compared with healthy volunteers, patients with sepsis had elevated levels of TNF-α and sTNFR I. Conclusions: The data indicate that a higher fraction of PBMCs was undergoing apoptosis in vivo in patients than controls. Enhanced in vitro apoptosis has also been observed in patients with sepsis, suggesting that a greater number of mononuclear cells in the peripheral circulation of patients are preprogrammed in vivo to undergo apoptosis. The circulating levels of both TNF-α and sTNFR I from patients were significantly higher (P < 0.001) than controls. The increase in levels of TNF-α is proportional to that of sTNFR I (r = 0.908), indicating that sTNFR I may have a protective effect in the early stage of sepsis.