Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations in Chronic Pancreatitis: A Multicenter, Cross-Sectional Study

Authors

Kristyn Gumpper-Fedus
Kaylin Chasser
Valentina Pita-Grisanti
Molly Torok
Timothy Pfau
Thomas A Mace
Rachel M Cole
Martha A Belury
Stacey Culp
Phil A Hart
Somashekar G Krishna
Luis F Lara
Mitchell L Ramsey
William Fisher
Evan L Fogel
Chris E Forsmark
Liang Li
Stephen Pandol
Walter G Park
Jose Serrano
Stephen K Van Den Eeden
Santhi Swaroop Vege
Dhiraj Yadav
Darwin L Conwell
Zobeida Cruz-Monserrate
Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC)

Publication Date

4-1-2024

Journal

Clinical and Translational Gastroenterology

Abstract

Introduction: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations.

Methods: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear cells (PBMCs) from controls (n = 16), AP/RAP (n = 17), and CP (n = 15) were measured by cytometry by time-of-flight.

Results: Plasma NGAL was elevated in subjects with CP compared with controls (area under the curve [AUC] = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, body mass index, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared with CP without diabetes ( P < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower, whereas dihomo-γ-linolenic and adrenic acids were elevated in CP ( P < 0.05). Linoleic acid was elevated in CP with diabetes compared with CP subjects without diabetes ( P = 0.0471).

Discussion: Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.

Keywords

Humans, Male, Female, Lipocalin-2, Pancreatitis, Chronic, Middle Aged, Biomarkers, Adult, Cross-Sectional Studies, Leukocytes, Mononuclear, Aged, Fatty Acids, Linoleic Acid, Case-Control Studies

DOI

10.14309/ctg.0000000000000686

PMID

38284831

PMCID

PMC11042777

PubMedCentral® Posted Date

4-25-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes