PD-1 and PD-L1 Expression in Inflammatory Bowel Disease: A Paired Immunohistochemical Study

Abstract

Background/Objectives: The significance of the PD-1/PD-L1 immune checkpoint pathway in inflammatory bowel disease (IBD) is highlighted by side effects from checkpoint inhibitor therapies including autoimmune enterocolitis reminiscent of IBD. Methods: This exploratory study examined PD-1 and PD-L1 expression in active versus inactive IBD in patients with Crohn’s disease (CD) or ulcerative colitis (UC). Immunohistochemical expression was analysed in biopsies obtained during active and inactive IBD from 28 patients (21 UC, 7 CD) using digital image analysis (DIA) and pathologist assessment. Correlations with endoscopic, histological, clinical and laboratory measures were evaluated. Results: PD-1 expression was sparse and precluded further statistical analysis. PD-L1 expression was significantly increased in active IBD compared to inactive IBD (p < 0.05) in both standard pathologist assessment and DIA. No statistically significant difference in PD-L1 expression was detected between UC and CD, although the small CD subgroup limited the power of this comparison. PD-L1 expression score positively correlated with endoscopic and histopathological inflammatory severity, stool frequency, and daily number of bloody stools. Faecal calprotectin level correlated with PD-L1 expression graded through standard pathologist assessment, but not with DIA. Standard pathologist assessment of PD-L1 expression correlated significantly with DIA PD-L1 scoring. Conclusions: In this small exploratory IBD cohort, mucosal PD-L1 expression was higher during active disease and was associated with several measures of inflammatory activity. These findings support further investigation of the PD-1/PD-L1 pathway in intestinal inflammation. DIA provided complementary quantitative assessment of PD-L1 expression.