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: Introduction: This review summarises current biologic agents commonly used in the treatment of uveitis. Methods: A literature search was conducted using the PubMed interface, looking specifically at randomised controlled studies, retrospective studies and case reports involving the use of biologic agents in the treatment of ocular inflammation. The following key words were used: uveitis, biologic agents, ocular inflammatory disease, pathophysiology and uveitis. In addition, relevant information was also included from selected ophthalmology textbooks. Results: A variety of biologic agents are being applied to the treatment of ocular inflammation. Randomised controlled trials addressing the use of such agents are lacking but there exist several case reports and case series studies which show the targeted therapeutic efficacy of various biologic agents tailored to the pathophysiology of ocular inflammatory disease. Conclusion: Biologic therapies provide clinicians with new, alternative treatment options for treating sight- threatening refractory uveitis, avoiding the side effects of long-term corticosteroid and steroid- sparing agent use. Ann Acad Med Singapore 2007;36(Suppl):31-9
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ABSTRACT: Acute anterior uveitis (AAU) is the most common form of uveitis and is thought to be autoimmune in nature. Recent studies have described genes that act as master controllers of autoimmunity. Protein tyrosine phosphatase type 22 (PTPN22) and Cytotoxic T lymphocyte antigen-4 (CTLA-4) are two of these genes, and single nucleotide polymorphisms (SNPs) in the genes encoding these molecules have been associated with several autoimmune diseases. In this study we have analyzed SNPs in PTPN22 and CTLA-4 in patients with AAU. The functional protein tyrosine phosphatase type 22 (PTPN22) SNP (R620W rs2476601, 1858C/T), and two CTLA-4 SNPs (rs5742909, -318C/T and rs231775, 49A/G) were analyzed in 140 patients with AAU and 92 healthy controls by sequence-specific primer -polymerase chain reaction (SSP-PCR). Data was analyzed by chi(2) analysis and Fisher's exact test. There was no significant association between PTPN22 620W, CTLA-4 -318C/T, or CTLA-4 49A/G and AAU. Similarly, there was no association with the three SNPs when patients were classified by race or gender. Finally, there was no association with the presence of ankylosing spondylitis in the patient cohort. The data do not support an association between SNPs in PTPN22 and CTLA-4, genes regarded as genetic master switches of autoimmunity. This raises the issue of the etiology of AAU and the possibility that it should be regarded as an autoinflammatory rather than an autoimmune condition.Molecular vision 02/2009; 15:208-12. · 2.25 Impact Factor
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ABSTRACT: To determine whether rubella virus is involved in the pathogenesis of Fuchs heterochromic iridocyclitis (FHI). Fourteen patients (14 eyes) diagnosed with FHI based on characteristic ocular manifestations and eight control subjects were studied. Aqueous humor (AH) samples from 14 FHI patients and one vitreous sample from a FHI patient were analyzed for intraocular antibody production against rubella virus by calculation of the Goldmann-Witmer coefficient (GWC). Viral detection by nested polymerase chain reaction and isolation by culture in RK-13 cells were conducted in nine FHI patients. In addition to laboratory examinations, medical history of rubella virus vaccination was also obtained. Ten patients with FHI examined showed intraocular synthesis of rubella virus antibodies (GWC > 3). A high index of rubella virus antibody production was also found in the vitreous sample (GWC = 30.6). GWC in all control subjects were below detectable level. The rubella genome was detected in two of nine patients, and rubella virus was isolated from one of nine patients with FHI. None of the patients with FHI had been vaccinated against rubella. Our laboratory data strongly suggest a relationship between FHI and rubella virus.Albrecht von Graæes Archiv für Ophthalmologie 10/2010; 248(10):1487-91. DOI:10.1007/s00417-010-1434-6 · 2.33 Impact Factor