Distinct Serum Immune Profiles Define the Spectrum of Acute and Chronic Pancreatitis From the Multicenter Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) Study

Bomi Lee; Elaina K Jones; Murli Manohar; Liang Li; Dhiraj Yadav; Darwin L Conwell; Phil A Hart; Santhi Swaroop Vege; Evan L Fogel; Jose Serrano; Dana Andersen; Melena D Bellin; Mark D Topazian; Stephen K Van Den Eeden; Stephen J Pandol; Chris E Forsmark; William E Fisher; Walter G Park; Sohail Z Husain; Aida Habtezion; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC)

doi:10.1053/j.gastro.2023.03.236

Distinct Serum Immune Profiles Define the Spectrum of Acute and Chronic Pancreatitis From the Multicenter Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) Study

Gastroenterology. 2023 Jul;165(1):173-186. doi: 10.1053/j.gastro.2023.03.236. Epub 2023 Apr 14.

Authors

Bomi Lee¹, Elaina K Jones², Murli Manohar², Liang Li³, Dhiraj Yadav⁴, Darwin L Conwell⁵, Phil A Hart⁶, Santhi Swaroop Vege⁷, Evan L Fogel⁸, Jose Serrano⁹, Dana Andersen⁹, Melena D Bellin¹⁰, Mark D Topazian⁷, Stephen K Van Den Eeden¹¹, Stephen J Pandol¹², Chris E Forsmark¹³, William E Fisher¹⁴, Walter G Park¹⁵, Sohail Z Husain¹⁶, Aida Habtezion¹⁷; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC)

Collaborators

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

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, School of Medicine, Stanford University, Stanford, California. Electronic address: bomilee@stanford.edu.
² Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, School of Medicine, Stanford University, Stanford, California.
³ Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas.
⁴ Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
⁵ Department of Internal Medicine, University of Kentucky, Lexington, Kentucky.
⁶ Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio.
⁷ Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
⁸ Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
⁹ Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
¹⁰ Division of Pediatric Endocrinology, University of Minnesota, Minneapolis, Minnesota.
¹¹ Division of Research, Kaiser Permanente Northern California, Oakland, California.
¹² Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, California.
¹³ Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida.
¹⁴ Division of General Surgery, Baylor College of Medicine, Houston, Texas.
¹⁵ Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California.
¹⁶ Division of Pediatric Gastroenterology, Hepatology, and Nutrition, School of Medicine, Stanford University, Stanford, California.
¹⁷ Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California. Electronic address: aidah@stanford.edu.

PMID: 37061168
PMCID: PMC10330331 (available on 2024-07-01)
DOI: 10.1053/j.gastro.2023.03.236

Abstract

Background & aims: Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis.

Methods: Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) consortium. Samples (N = 231) were obtained from individuals without pancreatic disease (n = 56) and from those with chronic abdominal pain (CAP) (n = 24), AP (n = 38), RAP (n = 56), and CP (n = 57).

Results: A total of 33 immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to interleukin (IL) 17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL17A and C-C motif chemokine ligand 20 differentiated CP from CAP, suggesting the involvement of T helper 17 cells in CP pathogenesis. The receiver operator characteristic curve with 2 immune markers (IL17A and sulfotransferase 1A1) could differentiate CP from CAP (optimistic area under the curve = 0.78). The macrophage classical activation pathway elevated along the continuum of pancreatitis, suggesting an accumulation of proinflammatory signals over disease progression. Several immune markers were associated with smoking, alcohol, and diabetes status.

Conclusions: Immune profiling of serum samples from a large pancreatitis cohort led to identifying distinct immune markers that could serve as potential biomarkers to differentiate the varying pancreatitis disease states. In addition, the finding of IL17 signaling in CP could provide insight into the immune mechanisms underlying disease progression.

Keywords: Alcohol; Immunity; Pancreatitis; Serum; Smoking.

Publication types

Multicenter Study

MeSH terms

Abdominal Pain
Acute Disease
Biomarkers
Diabetes Mellitus*
Disease Progression
Humans
Pancreatitis, Chronic* / diagnosis
Pancreatitis, Chronic* / epidemiology

Substances

Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding