Tim-3 Expression in Duodenal Mucosa: The Role in the Pathogenesis and Diagnosis of Celiac Disease As An İmmune Checkpoint Molecule

Limited data exist on the expression of immune checkpoint molecules (ICMs) in celiac disease (CD). This study aims to evaluate Tim-3 expression in duodenal biopsies from CD patients and those of non-CD patients, some of whom have increased intraepithelial lymphocytes (IELs). Duodenal tissues from 214 individuals who applied to the adult gastroenterology clinic were re-evaluated. The American College of Gastroenterology Guidelines were used to confirm the diagnosis of CD. Sections were prepared from formalin-fixed paraffin-embedded duodenal tissues for immunohistochemical analyses. The area with the highest Tim-3 expression in the lamina propria was counted at 40x (HPF) magnification. Receiver operating characteristic analysis offered a cut-off value predicting CD diagnosis as “>9 per HPF” (p<0.001, AUC: 0.744). High Tim-3 expression was associated with higher IEL numbers and a diagnosis of CD and correlated with endoscopic and serological findings of CD (p<0.001) in the whole cohort. In the CD group, a correlation was found between Tim-3 positive cell numbers and mean IEL counts (p=0.007, Spearman’s rho: 0.279). On the other hand, no difference was detected between Tim-3 expression and Marsh types (p=0.291), serum tTG (p=0.482), and EMA (p=0.765) titers in CD patients. In the non-CD group, Tim-3 expression was unaffected by either the increase in IEL or gastric Helicobacter pylori infection. In this study, we first demonstrated the expression profile of Tim-3 in the duodenal mucosa as an ICM. Confirmation of these findings with further analyses will provide a better understanding of the inflammatory cycle in the duodenal mucosa and new insights into diagnosing and understanding CD pathogenesis.