Circulating Immune Signatures Across Clinical Stages of Chronic Pancreatitis: A Pilot Study

Authors

Rasmus Hagn-Meincke
Phil A Hart
Dana K Andersen
Santhi S Vege
Evan L Fogel
Jose Serrano
Melena D Bellin
Mark D Topazian
Darwin L Conwell
Liang Li
Stephen K Van Den Eeden
Asbjørn M Drewes
Stephen J Pandol
Chris E Forsmark
William E Fisher
Dhiraj Yadav
Søren S Olesen
Walter G Park
Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC)

Publication Date

2-1-2024

Journal

European Journal of Gastroenterology & Hepatology

DOI

10.1097/MEG.0000000000002691

PMID

38047728

PMCID

PMC10842751

PubMedCentral® Posted Date

2-1-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Interleukin-8, Interleukin-6, Pilot Projects, Cross-Sectional Studies, Cytokines, Pancreatitis, Chronic, Chemokines, Diabetes Mellitus

Abstract

OBJECTIVE: This pilot study seeks to identify serum immune signatures across clinical stages of patients with chronic pancreatitis (CP).

METHODS: We performed a cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies-study. CP subjects were categorised into three clinical stages based on the presence/absence of metabolic complications: (1) CP with no diabetes and exocrine pancreatic dysfunction (EPD), (2) CP with either diabetes or EPD, and (3) CP with diabetes and EPD. Blinded samples were analysed using an 80-plex Luminex assay of cytokines/chemokines/adhesion molecules. Group and pairwise comparisons were performed to characterise immune signatures across CP subgroups.

RESULTS: A total of 135 CP subjects (evenly distributed between clinical stages) and 50 controls were studied. Interleukin-6 (IL-6), interleukin-8 (IL-8), and soluble intercellular adhesion molecule 1 (sICAM-1) were significantly elevated in CP subjects compared to controls. The levels of IL-6 and IL-8 increased with advancing disease stages, with the highest levels observed in CP with diabetes and EPD (clinical stage 3). Furthermore, hepatocyte growth factor and macrophage-derived chemokine were significantly increased in clinical stage 3 compared to controls.

CONCLUSION: Our study reveals a progressive elevation in pro-inflammatory cytokines and chemokines with advancing clinical stages of CP. These findings indicate potential targets for the development of disease-modifying interventions.