T helper 1 type cytokines polymorphisms: Association with susceptibility to Behçet's disease
Department of Physical Medicine and Rehabilitation, Medical Faculty, Ondokuz Mayis University, Samsun, Turkey. Clinical Rheumatology
(Impact Factor: 1.7).
08/2007; 26(8):1299-305. DOI: 10.1007/s10067-006-0503-z
The pathogenesis of Behçet's disease (BD) is not fully understood and immunological abnormalities and genetic factors have been investigated. Because serum concentrations of mainly T helper 1 (Th1) type cells have been reported to be increased in BD, we aimed to investigate whether certain cytokine polymorphisms might represent a risk factor for developing BD. We genotyped 80 patients with BD and 105 healthy controls for interleukin (IL)-1 α (T/C -889), IL-1 β (C/T -511, T/C +3962), IL-1R (C/T pst11970), IL-1RA (T/C mspa111100), IL-2 (T/G -330), IL-12 (C/A -1188), interferon (IFN)- y (A/T UTR 5644), and TNF-α (G/A -238) polymorphisms. Analyses of cytokine polymorphisms were performed with PCR-SSP. The genotype and allele frequencies of the patients and controls were compared and the association between the polymorphisms of the cytokines with the clinical findings was investigated. Genotype distribution showed significant differences between the patients and the controls for the IL-1α -889, IL-17beta; -511, IL-1 β +3962, IL-1R, IL-12, IFN- y and TNF- α cytokines. We didn't observe significant difference in genotypic frequencies of IL-1RA and IL-2 in our study. Comparison of the IL-1 7alpha; -889, IL 1 β -511, and IL 1 β +3962 genotype frequencies showed significant increase in CC genotype between the patients and the controls. The individuals with IL-1R TT polymorphism had a higher risk for BD compared to patients with CT/CC polymorphism. Comparison of IL-12, IFN- y and TNF- α genotype frequencies showed significant increase in CA, AA, and AA genotypes between the patients and controls, respectively. The frequencies of genotypes according to the clinical features of the patients with BD did not show a significant difference (p > 0.05). Our study suggests that development of BD might be determined by various cytokine gene polymorphisms. However, further studies on larger numbers of cases are needed before definite conclusions can be drawn.
Available from: Imed Ben Ghorbel
- "Previous findings supported the notion that Th1 cytokines could play an important role in inflammation and tissue injury and are correlated with active BD [29,35]. Th17 cells also have a specific role in immune function through coordinated effector cytokine action . "
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ABSTRACT: To investigate plasma IL-17 level and the expression of Th17 cell transcription factor RORγt in the pathogenesis of Behçet's Disease (BD).
Blood samples were collected from 73 patients with BD (45 patients were in active stage), 20 systemic lupus erythematosus (SLE) and 12 multiple sclerosis patients (MS). Twelve patients with BD were investigated both in their active and remission stages. Samples were processed to detect IL-17A level in plasma by enzyme-linked immunosorbent assay (ELISA). Related gene expression was assessed by real-time reverse transcription polymerase chain reaction. Function of Th17 cells in active BD patients with erythema nodosum (EN)-like eruption was studied in relation to human umbilical vein endothelial cells (HUVECs).
We demonstrated the presence of Th17 cells and RORγt among the peripheral blood mononuclear cells (PBMC). The percentage of circulating Th17 cells and the ability to produce interleukin-17A (IL-17A) were increased in samples derived from patients with active BD, MS and SLE patients. We observed that IL-17A from patients with active BD could induce adhesion molecule messenger RNA expression in HUVECs.
RORγt determined Th17 cell might be involved with increased IL-17A in BD. Our results indicate that IL-17 contributes to the active proinflammatory pattern that is characteristic of inflammatory diseases and patients with active BD.
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ABSTRACT: Genetic factors predispose individuals to Behçet's disease (BD) and periodontal disease. IL-1 has been implicated in the pathogenesis of both BD and periodontal disease. The relationship between periodontitis and pathogenesis of BD has not yet been determined. Since IL-1 has been implicated in the pathogenesis of both BD and periodontal disease, we aimed to investigate the possible relation of the periodontal scores and SNPs of IL-1alpha-889C/T, IL-1beta-511C/T, and IL-1beta+3962T/C with BD compared to healthy controls (HC) and recurrent aphtous stomatitis (RAS). A total of 155 Turkish individuals were enrolled in this study. The periodontal status of all subjects was evaluated according to the WHO community periodontal index of treatment needs. For genotyping, CTS-PCR-SSP was employed. IL-1alpha-889C allele was significantly higher in BD patients (p = 0.03) and RAS (p = 0.02) compared to HC. The frequency of IL-1beta+3962T allele was significantly higher in RAS patients compared to HC (p = 0.015). Male gender (p = 0.04), age (p = 0.02) and carrying IL-1beta-511T allele (p = 0.01) were found to be a significant risk factors for higher periodontal scores in Turkish population. We can speculate that susceptibility to the development of periodontal disease could be influenced by IL-1 SNPs. Periodontitis-induced autoinflammatory response also may play a role in the development/severity of BD and RAS via IL-1 gene alteration.
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ABSTRACT: Behçet's Disease (BD) is a systemic immunoinflammatory disease. The pathogenesis of BD is unknown, although raised levels of several pro-inflammatory cytokines have been reported. Nuclear factor kappa B (NF-kappaB) is a family of critical transcriptional factors involved in the regulation of a large variety of inflammatory responses and apoptosis. In this study we investigated the -94 insertion/deletion ATTG promoter polymorphism of the NF-kappaB1 gene (NFKB1) in 86 patients with BD and 100 healthy controls. The frequency of the -94ins ATTG (I) allele was 61.6% in patients with BD and 59% in controls and the frequency of the -94 del ATTG (D) allele was 38.4% in patients with BD and 41% in controls. The frequency of the -94ins ATTG (I) allele was significantly higher in patients with ocular involvement (P = 0.03). In the genotype study, the overall frequencies of II, ID and DD were 40.7%, 41.9%, and 17.4% in the patient group and 30%, 58% and 12% in the control group (P: 0.08). The II genotype was significantly higher in patients with ocular involvement, genital ulcers or papulopustular lesions. The frequency of the II, ID and DD genotypes showed no marked difference in patients with erythema nodosum, pathergy positivity, arthritis or vascular involvement. No difference was found for gender, positive family history or age at disease onset. This study provides evidence that the -94ins/del ATTG promoter polymorphism of NFKB1 may have functional consequences in BD, especially in patients with ocular involvement.
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