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R. Lee, L. P. Schewitz, L. B. Nicholson, C. M. Dayan, A. D. Dick; Application of a Flow Cytometric Assay to Predict an Individual Patient’s Response to Glucocortoid Therapy for Posterior Segment Intraocular Inflammation (Uveitis). Invest. Ophthalmol. Vis. Sci. 2008;49(13):3234. doi: https://doi.org/.
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The clinical challenge of steroid refractory (SR) disease is common to a range of autoimmune conditions, including posterior segment intraocular inflammation (uveitis) and ulcerative colitis (UC). We recently identified a subpopulation of SR CD4+ T cells in patients with SR UC, and the purpose of this study was to determine whether this subpopulation is also present in patients with SR uveitis, and to pilot our in-vitro assay as a predictive test of steroid responsiveness in uveitis patients.
PBMCs from 27 uveitis patients were cultured for 5 days with CD3 / CD28 in the presence of supratherapeutic concentrations of dexamethasone. In-vitro steroid responsiveness was determined by the presence or absence of a CFSElow subpopulation of SR CD4+ cells (as we have previously reported). A masked investigator concurrently analysed a standard patient dataset to classify patients as clinically SR (threshold for disease reactivation was ≥10mg prednisone daily), and steroid sensitive (SS) (threshold was <10mg of prednisone daily). Agreement between the clinical and in-vitro measures of SR disease was then determined using the kappa statistic.
There was 78% agreement (21/27) between in-vitro assay and clinical definitions of SR and SS disease. Of the 6 cases (22%) that didn’t agree, 5 (18%) were in-vitro SS but clinically SR and 1 (4%) was in-vitro SR but clinically SS. This translates to a kappa coefficient of 0.56 (‘good’ agreement) with a p value of 0.002. Although specificity and sensitivity values for such a small sample should be interpreted with caution, these were 92% and 64% respectively, giving our in-vitro measure a positive predictive value of 90% and a negative predictive value of 71% for clinically defined SR disease.
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