Purchase this article with an account.
D. Atan, J. Plskova, L. Kuffova, A. Hogan, D. J. Kilmartin, J. V. Forrester, A. D. Dick, A. J. Churchill; Cytokine Gene Polymorphisms and Disease Susceptibility in Non-Infectious Uveitis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5183.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Non-infectious uveitis is mediated by CD4+ T helper1 (Th1) cells which produce pro-inflammatory cytokines like Tumour Necrosis Factor (TNF). The central pathogenic role of TNF in uveitis is well illustrated by the success of new biologic therapies that target either TNF or its receptors. Patients who respond to treatment show an increase in serum CD4+ IL10+ cells, where Interleukin 10 (IL10) is anti-inflammatory with an inhibitory effect on Th1 cells. Transcription of TNF and IL10 is influenced by genetic polymorphisms in their promoters, resulting in up-regulation of TNF by TNFB*2 & TNFα-308A, and down-regulation of IL10 by IL10 -1082A. Our aim was to determine whether these polymorphisms influenced susceptibility to uveitis.
86 patients were recruited to the study who met well defined clinical and/or pathological diagnostic criteria: 28 with sarcoid, 28 with Behçet’s, and 30 with multifocal choroiditis and panuveitis. 48 healthy controls with no history of autoimmune or inflammatory disease took part. All subjects were white Caucasians from the UK and Ireland. DNA was extracted from venous blood by standard methods. Genotyping of the TNFα -238A/G, TNFα -308A/G, TNFß*1/2, IL10 -1082A/G and IL10 -819T/C polymorphisms was performed using sequence specific primers and polymerase chain reaction. The X2 test was used to compare patient and control groups.
We did not find a significant association between any of the cytokine polymorphisms and disease susceptibility in our patient groups. Nor was there an association between IL10 proximal promoter haplotype and disease.
Non-infectious uveitis is a multifactorial polygenic disorder with protean manifestations. We therefore focused our study on 3 syndromes with well defined diagnostic criteria. We have previously shown an association between TNF and IL10 promoter polymorphisms and disease severity in sympathetic ophthalmia. This study shows that there is no association with disease susceptibility in these 3 uveitic syndromes. This may be because cytokines have less influence on disease initiation, but become important during the chronic phase of disease when they are responsible for sustaining the inflammatory response and maintaining pathogenic T cells. We therefore propose to take this work further to consider the influence of these polymorphisms on disease severity and outcome.
This PDF is available to Subscribers Only