P053 Ustekinumab decreases circulating Th1, Th17, and MAIT cells in Crohn’s disease

Abstract Background Ustekinumab is a humanized antibody to p40 subunit shared by the cytokines IL-12 and IL-23, which has been approved for treatment of Crohn’s disease. While it presumed derive clinical efficacy blocking ability these stimulate specific T cell subsets, its actual effect upon human immune system not well-described. Methods Peripheral blood mononuclear cells (PBMC) were cryopreserved from 20 patients before during ustekinumab therapy. Thawed PBMC then analyzed flow cytometry surface markers and, after overnight stimulation, intracellular cytokines. Success (n=9) or failure (n=11) therapy was at discretion treating physician, blinded data. Results A significant decrease in IL-17A-producing Th17 (p=0.001) CD161+/TCRVα7.2+ MAIT (p=0.005) seen overall response ustekinumab. no IFN-γ -producing CD4 (Th1) CD8 cells, there dichotomy between responders non-responders, with Th1 decreasing (p=0.004) increasing non-responders (p=0.03) initiation. IFN-γ+ likewise increased (p=0.01), although their less (p=0.12). difference pre-treatment frequency Th17’s significantly more common (p=0.03). Conclusion IL-23-blocking on across all recipients, IL-12-blocking IFN-γ-producing restricted treatment-responsive patients, suggesting that mechanism action may differ newer, IL-23-specific agents. Whether rise can predict warrants additional study.