Correlation between DPP-4 Gene Expression and T-Cell Subset Marker Genes in Chronic Liver Disease Patients in Eastern India: An Observational Study.

Abstract

Introduction: The role of dipeptidyl peptidase-4 (DPP-4/CD26) in chronic liver disease (CLD) remains incompletely understood, particularly its interaction with immune cells. This study investigates the association between DPP-4 gene expression and T-cell subset marker genes in CLD patients, aiming to elucidate potential immunological mechanisms underlying disease progression.

Methods: A total of 130 individuals were enrolled across four groups: non-alcoholic fatty liver disease (NAFLD; n = 46), non-alcoholic cirrhosis (NAC; n = 23), alcoholic cirrhosis (ALC; n = 21), and healthy controls (n = 40). Peripheral blood samples were analysed for biochemical parameters and DPP-4 activity. Gene expression profiling was conducted in peripheral blood mononuclear cells to assess DPP-4 and T-cell marker genes (TBX21, RORC, GATA3, FOXP3, and CD3D).

Results: DPP-4 expression was elevated in all CLD subgroups, reaching statistical significance in NAFLD (P = 0.0142). The Th1 marker TBX21 showed increased expression, significantly in NAC (P = 0.0091), and demonstrated a strong correlation with DPP-4 in non-alcoholic CLD. The Th17 marker RORC was significantly elevated in NAFLD (P = 0.016), whereas the Th2 marker GATA3 and the Treg marker FOXP3 were significantly reduced (P = 0.0049 and P = 0.0028, respectively), with FOXP3 showing a negative correlation with DPP-4 (r = 0.588). CD3D expression correlated with DPP-4 in ALC patients.

Conclusion: These findings suggest disrupted regulatory coordination rather than uniform Treg suppression across CLD subgroups. NAFLD exhibited partial Th17 polarisation, whereas NAC may reflect Th17 exhaustion. DPP-4 appears to be associated with Th1 responses and may contribute to liver injury in NAC.