P379 PD-1-positive cells contribute to the diagnosis of Inflammatory Bowel Disease and can aid in predicting response to vedolizumab

Abstract

Abstract Background Differentiating inflammatory bowel disease (IBD) from other inflammatory diseases is often challenging. Programmed cell death protein-1 (PD-1) is expressed in T cells and is an indicator of their exhaustion. The role of PD-1 expression in diagnosing IBD and predicting the response of biologic agents remains inconclusive. Methods In this study, endoscopic biopsy samples of 19 patients diagnosed with IBD and other inflammatory diseases were analysed using multiplexed immunohistochemistry . Other inflammatory diseases comprised five patients with intestinal tuberculosis, and five with intestinal Behçet’s disease. Additionally, a separate prospectively maintained "vedolizumab (VDZ) cohort", established in 12 ulcerative colitis(UC) patients who underwent endoscopic biopsy before VDZ administration was analysed to predict response to VDZ. Results In the immunohistochemistry analysis, the cell density of T cell subsets, including helper T cell (Th), cytotoxic T cell (Tc), regulatory T cell (Treg), PD-1+ cell, PD-1+ Th, PD-1+ Tc, and PD-1+ Treg was investigated and compared between IBD and other inflammatory disease. Cell densities of PD-1+ cells (p=0.028), PD-1+ Th (p=0.008), and PD-1+ Treg (p=0.024) were higher in IBD compared with other inflammatory disease.(Figure 1) In addition, the proportion of PD-1+ cells in Th and Treg was higher in the IBD group than in the other inflammatory disease group (median 7% vs. 3%, p=0.008; median 6% vs. 2%, p=0.004, respectively). Comparing within IBD, the cell density of Treg was higher in Crohn’s disease(CD) than in UC (p=0.042), whilst the cell density of Tc was higher in CD than in UC with marginal statistical significance (p=0.066). In the VDZ cohort, patients with a 14-week steroid-free clinical response had higher levels of PD-1+ cells (p=0.026), PD-1+ Th (p=0.026), and PD-1+ Treg (p=0.041) than the no response group.(Table 1) Conclusion We explored the relationship between PD-1 expression and IBD using multiplexed immunohistochemistry. We compared IBD and other inflammatory disease in their expression of various immune cells including PD-1+ cells, and found IBD had higher PD-1 expression, as well as higher PD-1+ Th and PD-1+ Treg compared with other inflammatory diseases. In addition, VDZ-responsive patients had higher PD-1 expression. Our study confirmed the difference in PD-1 expression in IBD and other inflammatory diseases and revealed that PD-1 expression could be a predictive marker for VDZ responsiveness.