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Ae Ra Kee, Paul Edward Hutchinson, John Edward Connolly, Nobuyo Yawata, Jay Siak, Rupesh Vijay Agrawal; Singapore Ocular Tuberculosis Immunity Study (SPOTIS). Invest. Ophthalmol. Vis. Sci. 2019;60(9):859.
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© ARVO (1962-2015); The Authors (2016-present)
Peripheral blood lymphocyte profiling has been shown to be useful in discriminating disease activity of tuberculosis (TB). We conducted a prospective multicenter clinical study where we used polychromatic flow cytometry to look for any variance of CD4+ T cells in different phenotypic presentations of ocular TB, and to analyse if these biomarkers can be used as a predictive marker between treatment responders and non-responders.
A total of 36 Asian patients with presumed diagnosis of ocular TB, with either positive mycobacteria-specific interferon gamma release assays or positive tuberculin skin test, were recruited from tertiary eye care centers in Singapore over a period of 18 months. 8 subsequently received anti-tuberculosis treatment (ATT). T-lymphocyte profiling (CD4+CD154+TNFa+.) using HLA-DR, CD27 and CD38 was performed for all patients after induction with purified protein derived antigen (PPD), where blood samples were taken on recruitment, MTB antigen specific CD4 assay was set up, and flow cytometric data was analysed using FlowJo software.
Of the 44 eyes of the 36 patients, there was no significant difference in the proportion of PPD incuded CD4+CD154+TNFa+ cells between patients presenting with anterior or posterior uveitis for expression of CD27-CD38+(p=0.27) , CD27-HLADR+ (p=0.83). HLA DR+CD38+(p=0.85),CD27- (p=0.40), CD27-GMCSF+(p=0.11). We found no significant difference in the proportion of MTB antigen specific CD4+ T cells between the treated and non-treated groups for expression of CD27-CD38+(p=0.84) , CD27-HLADR+ (p=0.44). HLA DR+CD38+(p=0.73),CD27- (p=0.82), CD27-GMCSF+(p=0.30). Of the 8 subjects treated with ATT, 3 had a clinical response and 5 did not. Comparing between the responders and non-responders, we found that there was no significant difference between them in the proportion of CD4+ T cells specific for PPD or ESAT-6+CFP-10. We also found that although the activation phenotype of the PPD responding cells was not overall significantly different, 2 of the subjects who had initially high levels of these markers had low post treatment levels.
Our study is the first of its kind to look into T cell lymphocyte profiling of serum sample in patients with ocular TB, and thus far, no significance of CD4 T cells was found. More future studies need to be undertaken to assess the value of CD4+ T cell phenotypes and their level as a biomarker for analysing ocular TB.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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