Significance of PD1 Alternative Splicing in Celiac Disease as a Novel Source for Diagnostic and Therapeutic Target

Abstract

This study examines the role of the PD-1/PD-L1 pathway in celiac disease (CD), focusing on its involvement in immune regulation and the impact of altered mRNA splicing on identifying new diagnostic, prognostic, and therapeutic targets. The findings revealed an overexpression of the sPD-1 protein and the PD-1Dex3 transcript in CD. Three novel spliced isoforms were identified: two producing truncated proteins and one encoding a soluble PD-1 variant (sPD-1) due to a loss of exon 3 and part of exon 2. These results suggest that dietary gluten influences cell homeostasis by modulating pre-mRNA splicing of key regulatory proteins, serving as an adaptive response to dietary changes.