Calcitriol (1α,25-dihydroxyvitamin D3) is the active vitamin D metabolite and mediates immunological functions, which are relevant in allergy. Its therapeutic use is limited by hypercalcaemic toxicity. We have previously shown that the activation of the vitamin D receptor inhibits IgE production and that B cells can synthesize calcitriol from its precursor 25-hydroxyvitamin D3 (inactive precursor) [25(OH)D] upon antigenic stimulation. In this study, we address the impact of 25(OH)D on the development of type I sensitization and determine its role in allergen-specific immunotherapy. BALB/c mice were sensitized to OVA, under 25(OH)D-deficient or sufficient conditions. The humoral immune response over time was measured by ELISA. OVA-specific immunotherapy was established and studied in a murine model of allergic airway inflammation using lung histology, pulmonary cytokine expression analysis, and functional parameters in isolated and perfused mouse lungs. In 25(OH)D-deficient mice, OVA-specific IgE and IgG1 serum concentrations were increased compared with control mice. OVA-specific immunotherapy reduced the humoral immune reaction after OVA recall dose-dependently. Coadministration of 25(OH)D in the context of OVA-specific immunotherapy reduced the allergic airway inflammation and responsiveness upon OVA challenge. These findings were paralleled by reduced Th2 cytokine expression in the lungs. In conclusion, 25(OH)D deficiency promotes the development of type I sensitization and correction of its serum concentrations enhances the benefit of specific immunotherapy.

IntroductionIn the present study, we sought to identify markers in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) that distinguish those achieving remission at 6 months following rituximab or cyclophosphamide treatment from those for whom treatment failed in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial.MethodsClinical and flow cytometry data from the RAVE trial were downloaded from the Immunology Database and Analysis Portal and Immune Tolerance Network TrialShare public repositories. Flow cytometry data were analyzed using validated automated gating and joined with clinical data. Lymphocyte and granulocyte populations were measured in patients who achieved or failed to achieve remission.ResultsThere was no difference in lymphocyte subsets and treatment outcome with either treatment. We defined a Granularity Index (GI) that measures the difference between the percentage of hypergranular and hypogranular granulocytes. We found that rituximab-treated patients who achieved remission had a significantly higher GI at baseline than those who did not (p = 0.0085) and that this pattern was reversed in cyclophosphamide-treated patients (p = 0.037). We defined optimal cutoff values of the GI using the Youden index. Cyclophosphamide was superior to rituximab in inducing remission in patients with GI below −9.25 % (67 % vs. 30 %, respectively; p = 0.033), whereas rituximab was superior to cyclophosphamide for patients with GI greater than 47.6 % (83 % vs. 33 %, respectively; p = 0.0002).ConclusionsWe identified distinct subsets of granulocytes found at baseline in patients with AAV that predicted whether they were more likely to achieve remission with cyclophosphamide or rituximab. Profiling patients on the basis of the GI may lead to more successful trials and therapeutic courses in AAV.Trial registrationClinicalTrials.gov identifier (for original study from which data were obtained): NCT00104299. Date of registration: 24 February 2005.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0778-z) contains supplementary material, which is available to authorized users.

Most of today's video game strategies are based on a static set of game controls and player actions that remain oblivious to the player's context and own creativity. Building Upon Everyday Play is the result of a collaboration of Control Freaks, a pervasive gaming experience project, and Exemplar, a toolkit that uses programming-by-demonstration to author sensor-based interactions. In combination, Building Upon Everyday Play furthers a pervasive gaming experience through appropriation of objects in the player's environment and enables new ways to play.The project consists of a combination of a portable, wireless motion-sensing clamp that can be attached to everyday objects to turn them into game controllers by proxy, and a programming-by-demonstration system that translates sensor data reported by the controller into game events. In the demonstration, participants will be able to play custom video games projected on a large 2D screen by attaching the clamp to their bodies or provided household objects, and to invent their own moves to control the provided games.