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.


Journal

Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630

Informations de publication

Date de publication:
Jul 2023
Historique:
received: 14 11 2022
revised: 21 03 2023
accepted: 30 03 2023
pmc-release: 01 07 2024
medline: 26 6 2023
pubmed: 16 4 2023
entrez: 15 4 2023
Statut: ppublish

Résumé

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. 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). 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. 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.

Sections du résumé

BACKGROUND & AIMS OBJECTIVE
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 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 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 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.

Identifiants

pubmed: 37061168
pii: S0016-5085(23)00594-2
doi: 10.1053/j.gastro.2023.03.236
pmc: PMC10330331
mid: NIHMS1893093
pii:
doi:

Substances chimiques

Biomarkers 0

Types de publication

Multicenter Study Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

173-186

Subventions

Organisme : NIDDK NIH HHS
ID : U01 DK108288
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK108323
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK108332
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK108326
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK126300
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK108320
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK126365
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK108328
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK108300
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK108306
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK108314
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK108327
Pays : United States

Investigateurs

Liang Li (L)
Dhiraj Yadav (D)
Darwin L Conwell (DL)
Phil A Hart (PA)
Santhi Swaroop Vege (SS)
Evan L Fogel (EL)
Jose Serrano (J)
Dana Andersen (D)
Melena D Bellin (MD)
Mark Topazian (M)
Stephen K Van Den Eeden (SK)
Stephen J Pandol (SJ)
Chris Forsmark (C)
William E Fisher (WE)
Walter G Park (WG)

Informations de copyright

Copyright © 2023 AGA Institute. All rights reserved.

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Auteurs

Bomi Lee (B)

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.

Elaina K Jones (EK)

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.

Murli Manohar (M)

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.

Liang Li (L)

Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas.

Dhiraj Yadav (D)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.

Darwin L Conwell (DL)

Department of Internal Medicine, University of Kentucky, Lexington, Kentucky.

Phil A Hart (PA)

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio.

Santhi Swaroop Vege (SS)

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Evan L Fogel (EL)

Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.

Jose Serrano (J)

Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.

Dana Andersen (D)

Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.

Melena D Bellin (MD)

Division of Pediatric Endocrinology, University of Minnesota, Minneapolis, Minnesota.

Mark D Topazian (MD)

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Stephen K Van Den Eeden (SK)

Division of Research, Kaiser Permanente Northern California, Oakland, California.

Stephen J Pandol (SJ)

Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, California.

Chris E Forsmark (CE)

Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida.

William E Fisher (WE)

Division of General Surgery, Baylor College of Medicine, Houston, Texas.

Walter G Park (WG)

Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California.

Sohail Z Husain (SZ)

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, School of Medicine, Stanford University, Stanford, California.

Aida Habtezion (A)

Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California. Electronic address: aidah@stanford.edu.

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