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Rose Gilbert, Xiaozhe Zhang, Robert Sampson, Oren Tomkins-Netzer, Grazyna Galatowicz, Virginia L Calder, Susan Lightman; TIGIT+ Tregs May Be Associated with Clinical Remission of Non-Infectious Uveitis. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3313.
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© ARVO (1962-2015); The Authors (2016-present)
Uveitis is a significant but largely unrecognised cause of permanent visual impairment worldwide. T-regulatory cells (Tregs) have been shown to be involved in clinical remission of non-infectious uveitis and recently a role for the co-stimulatory molecule, TIGIT, in enhancing Treg-mediated suppression has been suggested. In this pilot prospective observational cohort study, we explore the hypothesis that peripheral blood levels of CD4+CD25+FoxP3+TIGIT+ Tregs are higher in noninfectious uveitis patients in clinical remission, induced by systemic immunosuppression, compared to those with active uveitis.
50 patients with noninfectious intermediate/ panuveitis, without identifiable associated systemic disease, attending clinics at Moorfields Eye Hospital, London, UK are being consecutively recruited to a prospective observational study between November 2014 and March 2016 for analysis of peripheral blood levels of Tregs and correlation with clinical activity. 30ml blood were obtained from 4 patients with active uveitis, 25 quiescent uveitis (≥6 months after discontinuation of systemic treatment) and 4 healthy control subjects. Peripheral blood mononuclear cells (PMBCs) were isolated by density gradient centrifugation and stained with fluorochrome-conjugated antibodies prior to analysis with the BD Fortessa flow cytometer to compare the percentage (%) co-expression levels of CD4, CD25, FoxP3 and TIGIT in the lymphocyte subset.
CD4+CD25+FoxP3+ Treg levels were higher in quiescent patients (n=25, mean 7.4%, range 6.1-9.6%) than active patients (n=4, mean 4.7%, range 3.9-6.5%). CD4+CD25+FoxP3+ Treg levels in the healthy subjects (n=4, mean 5.0%, range 3.37-6.61%) were similar to the active patients. However, TIGIT+ Tregs levels were higher in both the quiescent patients (mean 4.7%, range 3.2-7.6%) and healthy controls (mean 3.6%, range 2.8-4.3%), compared to the active uveitis patients (mean 2%, range 1.7-2.2%).
Preliminary study data suggests there are higher levels of TIGIT+ Tregs in the peripheral blood of uveitis patients in clinical remission and healthy controls, compared to patients with active disease. TIGIT could aid in identification of an immunosuppressive Treg subset which is associated with clinical remission in uveitis. Further patient recruitment to this study is currently ongoing and Treg functional assays are being performed to supplement the immunophenotypic data.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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