PURPOSE: Sympathetic ophthalmia (SO) is a prototypical autoimmune disease in which injury to one eye causes sight-threatening inflammation in the otherwise normal contralateral eye. Previous work found that human leukocyte antigen alleles HLA-DRB1*04 and DQA1*03 are markers of increased susceptibility and severity in British and Irish patients. Evidence is accumulating that single nucleotide polymorphisms (SNPs) in cytokine genes can also influence the development of autoimmune disease through their effect on levels of cytokine production. The purpose of this study was to determine whether polymorphisms in the cytokine genes are important markers for disease severity and outcome in patients with SO. METHODS: Twenty-six British and Irish patients meeting well-defined criteria for the diagnosis of SO were compared with 48 matched controls. Genotyping of SNPs in the TNFalpha, TNFbeta, and IL-10 genes was performed using the polymerase chain reaction and sequence-specific primers (SSP-PCRs) and of the CTLA-4 and TNF receptor 2 genes using restriction length polymorphism-PCR (RFLP-PCR). RESULTS: Significant associations were found between the IL-10 -1082 SNP and disease recurrence from previously stable disease and the level of steroids required for maintenance therapy. In addition, the GCC IL-10 promoter haplotype (IL-10 -1082G, -819C, -592C) was found to be protective against disease recurrence. CONCLUSIONS: These results show that cytokine gene polymorphisms are markers for the severity of disease in SO. They were found to be associated with recurrence of previously stable disease and with the level of maintenance steroid treatment required to control inflammatory activity.
PURPOSE: Sympathetic ophthalmia (SO) is a prototypical autoimmune disease in which injury to one eye causes sight-threatening inflammation in the otherwise normal contralateral eye. Previous work found that human leukocyte antigen alleles HLA-DRB1*04 and DQA1*03 are markers of increased susceptibility and severity in British and Irish patients. Evidence is accumulating that single nucleotide polymorphisms (SNPs) in cytokine genes can also influence the development of autoimmune disease through their effect on levels of cytokine production. The purpose of this study was to determine whether polymorphisms in the cytokine genes are important markers for disease severity and outcome in patients with SO. METHODS: Twenty-six British and Irish patients meeting well-defined criteria for the diagnosis of SO were compared with 48 matched controls. Genotyping of SNPs in the TNFalpha, TNFbeta, and IL-10 genes was performed using the polymerase chain reaction and sequence-specific primers (SSP-PCRs) and of the CTLA-4 and TNF receptor 2 genes using restriction length polymorphism-PCR (RFLP-PCR). RESULTS: Significant associations were found between the IL-10 -1082 SNP and disease recurrence from previously stable disease and the level of steroids required for maintenance therapy. In addition, the GCC IL-10 promoter haplotype (IL-10 -1082G, -819C, -592C) was found to be protective against disease recurrence. CONCLUSIONS: These results show that cytokine gene polymorphisms are markers for the severity of disease in SO. They were found to be associated with recurrence of previously stable disease and with the level of maintenance steroid treatment required to control inflammatory activity.
Authors: J Fernando Arevalo; Reinaldo A Garcia; Hassan A Al-Dhibi; Juan G Sanchez; Luis Suarez-Tata Journal: Middle East Afr J Ophthalmol Date: 2012-01
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