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Purpose: Myeloid dendritic cells (mDCs) play an important role in autoimmune diseases. However, the role of blood CD1c(+) myeloid dendritic cells 1 (mDC1s), the subset of human blood mDCs, is not well understood in noninfectious uveitis., Methods: Fresh peripheral blood samples from human noninfectious uveitis patients (n = 32) and healthy controls (HCs) (n = 64) were stained with FITC-Lineage 1 (Lin1), PERCP-HLADR, and PE-CD1c antibodies. The levels of mDC1 were quantified by using flow cytometric analysis. Longitudinal data from patients (n = 16) were analyzed to correlate the levels of mDC1 with disease activity., Results: Blood CD1c(+) mDC1 and its subpopulation, CD1c(hi) mDC1, were increased in uveitis patients compared with HCs. Longitudinal data demonstrated that both the CD1c(+) mDC1 and CD1c(hi) mDC1 subpopulation reflected a dynamic change in clinical uveitis activity: CD1c expression was increased in active uveitis but decreased when uveitis became inactive., Conclusions: Given these observations, an alteration in blood CD1c(+) mDC1 and the CD1c(hi) mDC1 subpopulation could be a potential biomarker to monitor clinical uveitis activity within patients., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: A discrete subpopulation of steroid refractory (SR) CD4(+) T cells has recently been identified in patients with SR ulcerative colitis (UC). The purpose of this study was to test whether this subpopulation is also present in patients with clinically defined SR uveitis. As interleukin (IL)-2 experimentally mediates the SR phenotype, the combined effects of dexamethasone (Dex) and a range of IL-2 targeting immunosuppressive agents were also investigated., Methods: Peripheral blood mononuclear cells (PBMCs) from 27 patients with uveitis and 4 normal volunteers were cultured for 5 days with CD3-CD28 beads. In vitro steroid refractivity or responsiveness was determined by the presence or absence of a subpopulation of SR CD4(+) cells (as previously reported for UC) that continued to proliferate or not in the presence of Dex. The patients were concurrently classified by a masked investigator as having clinically SR (threshold for disease reactivation, >or=10 mg prednisone daily) or steroid sensitive (SS) disease., Results: There was 78% (21/27) agreement between the in vitro and clinical classifications of SR and SS disease (kappa coefficient = 0.56, P = 0.002). This finding corresponds to a positive predictive value of 90% and a negative predictive value of 71%. In normal volunteers, basiliximab, daclizumab, and AG490 achieved an equivalent augmentation of CD4(+) cell suppression in combination with Dex., Conclusions: As in UC, patients with SR uveitis have a subpopulation of SR CD4(+) cells that are a potential target for intervention with anti-IL-2 therapies, including inhibitors of JAK/STAT signaling. The identification of SR T cells also has potential clinical application as a biomarker for SR disease.