Association of Single Nucleotide Polymorphisms in Toll-like Receptor Genes With Asthma Risk: a Systematic Review and Meta-analysis

PURPOSE: Asthma is a complex disease, with contributions from multiple genes, various genetic backgrounds, and environmental factors. Many human epidemiological studies have demonstrated that single nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes are inconsistently associated with asthma risk. Some have demonstrated differences concerning the study design and effect size, and conflicting results have been reported. A meta-analysis is necessary to determine the magnitude of this association. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic search and meta-analysis of the literature was conducted to estimate the association of SNPs in TLR genes with asthma risk. We screened the medical literature based on the following keyword searches in MEDLINE and EMBASE databases: 'TLR', 'polymorphism', 'asthma', and their combinations. RESULTS: Meta-analysis of eight studies on TLR4 Asp299Gly showed a marginal association of TLR4 with asthma risk (odds ratio [OR]=0.814 [95% confidence interval [CI], 0.652-1.016; P=0.069]) in the recessive model. TLR4 Thr399Ile was not associated with asthma risk under any genetic model. Meta-analysis of four studies on TLR2 Arg753Gln indicated that TLR2 might be significantly associated with asthma in the dominant and codominant models (P=0.029, P=0.030, and P=0.009, respectively). TLR9 -1237 was marginally associated with asthma risk (OR=0.408 [95% CI, 0.163-1.021; P=0.065]) in the codominant model. Analysis using the allele contrast model showed that the major TLR9 -1237 T allele tended to be a significant protective factor with OR=0.689 (95% CI, 0.471-1.007; P=0.055). CONCLUSIONS: The results showed that TLR4 Asp299Gly, TLR2 Arg753Gln, and TLR9-1237 might contribute significantly to asthma susceptibility. Future genetic association studies would consolidate these findings.

Does lowering hyperhomocysteinemia by folic acid beneficial for oculo-behcet's disease? a pilot study

To determine the effect of folic acid supplementation in Behset's disease [BD] patients with ocular involvement associated with hyperhomocysteinemia [Hhcys]. 19 BD patients, all with uveitis and/or retinal vasculitis associated with Hhcys [plasma hey > 15 /

Mimetisme moleculaire entre l'antigene-s et les peptides viraux

Experimental autoimmune uveitis [EAU], was induced in Lewis rats after injection of S- Antigen [S-Ag]. In this study we found an amino acid sequence homology between a uveitopathogenic site of S-Ag and two viral proteins. Based on our findings, we conclude that a viral infection may sensitize the mononuclear cells that can cross- react with self proteins by a mechanism termed molecular mimicry

Cellular autoimmunity to retinal specific antigens in Behcet's disease

Behcet's disease is characterised by a systemic disorders where autoimmune mechanisms play a role in its pathogenesis. Antigen S [Ag.S], interphotoreceptor retinoid protein [IRBP], and their respective uveitogenic peptides M, N, and R-4, R-14, caused on experimental autoimmune uveoretinitis [EAU] in animals. In this context, we investigated the proliferation of peripheral blood T cells in response to Ag.S, IRBP and their peptides. Patients with BD with uveitis responded highly to S antigen, to peptide M and N, when compared to BD patients without uveitis and healthy controls. Lymphocytes from patients with BD with uveitis proliferate to IRBP as well as uveitis patients not associated to BD. The responses were inhibited by monoclonal antibodies anti-CD4, anti-HLADR and anti CD11 a, indicating the importance of these molecules in T cell mediated immunity with these ocular antigens. Our results supported the idea that autoimmunity to retinal specific antigens may play a role in the ocular inflammation in BD

Functional and phenotypic analysis of T cells cloned from the skin of patients with Behcet's disease

Activated T lymphocytes often accumulate in the dermis of patients with active Behcet's disease [BD] and may play a role in the development of skin lesions. We propagated and cloned these cells directly from skin biopsies in two active BD. The cloning frequency estimates were f = 0.20 T cells delived from the skin of BD versus f = 0.68 for autologous blood T lymphocytes. All of the 12 skin-derived BD clones were CD4+. Clonal analyses performed with CD4+ clones from BD patients showed that all skin-derived clones synthesized interferon-gamma [IFN-gamma: 80%], glycosarninoglycan- stimulatorty factor [GAG: 11%], when induced in vitro by concanavalin-A [ConA]. Skinderived clones produced tumor necrosis factor-alpha [TNF-a] at 60% level. Our results demonstrate that T lymphocytes obtained from the skin of patients with BD synthesized cytokines which could modulate functions the BD skin immune system

Autoantibodies against endothelial cells in patients with beehcet's disease correlation with pulmonary vasculitis

We studied the prevalence of antibodies against endothelial cells [AECA],subendothelial matrix [ECM] and its major component collagen type IV in the pathogenesis of Behcet's disease [BD], with pulmonary manifestations, to examine the possible role of these antibodies in the pathogenesis of this clinical feature. Fifty patients with BD were studied where ten were characterized by the presence of pulmonary manifestations. They were compared to 22 patients with systemic Lupus Erythematosus [SLE]and 15 healthy controls. The AECA and ECM were determined by an enzyme-linked immunosorbent assay [ELISA] using endothelial cells derived from human umbilical vein by collagenase digestion. AECA were detected in patients with active BD, and in patients with active SLE. LOW AECA-BI% levels were found in patients with BD in inactive stage. High AECA-BI% levels were found in active BD patients with pulmonary aneurysm. Anti-ECM was also significantly higher in BD patients and patients with vasculitis, compared to normal controls [BD 19.6 +/- 8.4%, vasculitis 29.7 +/- 10.8%, normal controls 8.2 +/- 5.4%, p < 0.01]. Anti-collagen type IV was found increased in BD patients with vasculitis [20.8 +/- 13.4%, p < 0.01] compared to BD patients in inactive stage and normal controls [10.7 +/- 12.3%; 9.7 +/- 8.6%]. AECA and ECM antibodies were correlated with the presence of pulmonary aneurysm in active BD. AECA antibodies seem to be a marker of the presence of active vasculitis in BD