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

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

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12 Scopus citations

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.

Original language	English
Pages (from-to)	173-186
Number of pages	14
Journal	Gastroenterology
Volume	165
Issue number	1
DOIs	https://doi.org/10.1053/j.gastro.2023.03.236
State	Published - Jul 2023

Bibliographical note

Publisher Copyright:
© 2023 AGA Institute

Funding

Funding The research reported in this publication was supported by National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers related to The Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) (U01DK108300, U01DK108328, U01DK108306, U01DK108327, U01DK108288, U01DK108323, U01DK126300, U01DK108332, U01DK108314, U01DK108320, and U01DK108326). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Conflicts of interest These authors disclose the following: Melena D. Bellin has financial relationships with Viacyte and Dexcom (research support), Insulet (Data Safety Monitoring Board member), and Ariel Precision Medicine (advisory board). Aida Habtezion is currently on leave from Stanford University. The remaining authors disclose no conflicts. Funding The research reported in this publication was supported by National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers related to The Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) (U01DK108300, U01DK108328, U01DK108306, U01DK108327, U01DK108288, U01DK108323, U01DK126300, U01DK108332, U01DK108314, U01DK108320, and U01DK108326). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funders	Funder number
Ariel Precision Medicine
Melena D. Bellin
National Institutes of Health (NIH)	U01DK108306, U01DK108328, U01DK108327, U01DK126300, U01DK108323, U01DK108326, U01DK108314, U01DK108320, U01DK108300, U01DK108288, U01DK108332
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute
National Institute of Diabetes and Digestive and Kidney Diseases
Stanford University

Keywords

Alcohol
Immunity
Pancreatitis
Serum
Smoking

ASJC Scopus subject areas

Hepatology
Gastroenterology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "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",

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",

author = "Bomi Lee and Jones, {Elaina K.} and Murli Manohar and Liang Li and Dhiraj Yadav and Conwell, {Darwin L.} and Hart, {Phil A.} and Vege, {Santhi Swaroop} and Fogel, {Evan L.} and Jose Serrano and Dana Andersen and Bellin, {Melena D.} and Topazian, {Mark D.} and {Van Den Eeden}, {Stephen K.} and Pandol, {Stephen J.} and Forsmark, {Chris E.} and Fisher, {William E.} and Park, {Walter G.} and Husain, {Sohail Z.} and Aida Habtezion and Mark Topazian and Chris Forsmark",

note = "Publisher Copyright: {\textcopyright} 2023 AGA Institute",

year = "2023",

month = jul,

doi = "10.1053/j.gastro.2023.03.236",

language = "English",

volume = "165",

pages = "173--186",

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T1 - 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

AU - Lee, Bomi

AU - Jones, Elaina K.

AU - Manohar, Murli

AU - Li, Liang

AU - Yadav, Dhiraj

AU - Conwell, Darwin L.

AU - Hart, Phil A.

AU - Vege, Santhi Swaroop

AU - Fogel, Evan L.

AU - Serrano, Jose

AU - Andersen, Dana

AU - Bellin, Melena D.

AU - Topazian, Mark D.

AU - Van Den Eeden, Stephen K.

AU - Pandol, Stephen J.

AU - Forsmark, Chris E.

AU - Fisher, William E.

AU - Park, Walter G.

AU - Husain, Sohail Z.

AU - Habtezion, Aida

AU - Topazian, Mark

AU - Forsmark, Chris

PY - 2023/7

Y1 - 2023/7

N2 - 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.

AB - 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.

KW - Alcohol

KW - Immunity

KW - Pancreatitis

KW - Serum

KW - Smoking

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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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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