A suggestive association of fuchs heterochromic cyclitis with cytotoxic T cell antigen 4 gene polymorphism.
ABSTRACT Fuchs heterochromic cyclitis (FHC) is a chronic inflammatory eye disease, usually presenting as unilateral anterior uveitis. Up to date no disease susceptibility genes have been described for FHC.
The allele frequency of HLA DRB1 and DQB1, polymorphisms of the tumour necrosis factor (TNF) alpha promoter region (-376, -308, -238), the promoter (-318), first exon (+49) and (AT)n repeat polymorphism of the cytotoxic T cell antigen 4 (CTLA4) gene were analysed in 44 FHC patients and 139 healthy controls.
The CTLA4 -318 C/T genotype was increased in FHC patients [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.4-6.5], as well as long CTLA4 (AT)n microsatellite alleles with more than 16 AT repeats (OR 2.6, 95% CI 1.3-5.3). A trend towards the -308 G/A TNF-alpha genotype was found in the patient cohort, whereas no difference in HLA class II allele distribution was observed. Conclusion:CTLA4 but not TNF-alpha or HLA class II DRB1 and DQB1 may represent a candidate gene for disease susceptibility in FHC.
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ABSTRACT: To determine whether rubella virus (RV) is involved in the pathogenesis of Fuchs heterochromic iridocyclitis (FHI). Retrospective patient-controlled study. Intraocular immunoglobulin G production against RV, herpes simplex virus (HSV), varicella zoster virus (VZV), and Toxoplasma gondii was determined in the aqueous humor of 14 patients with FHI, 13 control subjects with herpetic uveitis anterior, and 19 control subjects with ocular toxoplasmosis by calculation of the Goldmann-Witmer coefficient (GWC). All patients and control subjects were seropositive for RV. Intraocular antibody production (GWC >3) against RV was found in 13 of 14 patients (93%) with FHI. Intraocular antibody production against HSV, VZV, or T gondii was not detected. None of the control subjects with herpetic uveitis anterior or with toxoplasma chorioretinitis had a positive GWC for rubella virus (P < .0001, Fisher exact test). Rubella virus, but not HSV, VZV, or T gondii, is associated with FHI.American Journal of Ophthalmology 01/2006; 141(1):212-214. · 3.63 Impact Factor
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ABSTRACT: Fuchs uveitis syndrome (FUS) is typically a unilateral, chronic, low-grade inflammation of the anterior segment which manifests in young adulthood. It is underdiagnosed because of its variable clinical spectrum. Although it can mimic various forms of anterior uveitis, it is important to make the correct diagnosis, based on clinical grounds, because both the management and prognosis differ from those of other uveitides. While its etiology remains unknown, it is possible that the disease has multiple causes that lead through different pathogenic mechanisms to the same clinical entity. Although many patients do not require treatment, it is not a benign condition, as often perceived. The high incidence of glaucoma makes it mandatory that all patients with FUS should be screened at regular intervals, even if they are not being actively treated and are relatively asymptomatic.Der Ophthalmologe 08/2005; 102(7):733-42; quiz 743-4. · 0.53 Impact Factor
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ABSTRACT: CTLA-4, expressed mainly on activated T cells, helps maintain, through its inhibitory function, immune-system homeostasis. Polymorphisms in the CTLA-4 gene (CTLA4) are known to be important in several autoimmune diseases, including multiple sclerosis (MS). Here, we have performed genotyping for CTLA4 polymorphisms, and investigated expression by peripheral blood mononuclear cells of CTLA-4 mRNA and protein, in patients with MS and myasthenia gravis and in healthy controls. Expression levels for mRNA and protein were similar in the patient and control groups; however, there was a clear relationship between genotype and CTLA-4 expression. Specifically, individuals carrying thymine at position -318 of the CTLA4 promoter (T(-318)) and homozygous for adenine at position 49 in exon 1 showed significantly increased expression both of cell-surface CTLA-4 after cellular stimulation and of CTLA-4 mRNA in non-stimulated cells. The association was seen most clearly for unsorted CD3(+) cells and was absent in the CD8(+) subset. The T(-318) allele has been shown to be negatively associated with susceptibility to MS in an earlier study by our group. Thus, we propose that the susceptibility-influencing role of CTLA4 in MS may be related to genotypically conditioned promoter function, whereby high gene expression may decrease the risk of disease.Genes and Immunity 06/2001; 2(3):145-52. · 3.68 Impact Factor