TY - JOUR
T1 - Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations in Chronic Pancreatitis
T2 - A Multicenter, Cross-Sectional Study
AU - on behalf of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC
AU - Gumpper-Fedus, Kristyn
AU - Chasser, Kaylin
AU - Pita-Grisanti, Valentina
AU - Torok, Molly
AU - Pfau, Timothy
AU - Mace, Thomas A.
AU - Cole, Rachel M.
AU - Belury, Martha A.
AU - Culp, Stacey
AU - Hart, Phil A.
AU - Krishna, Somashekar G.
AU - Lara, Luis F.
AU - Ramsey, Mitchell L.
AU - Fisher, William
AU - Fogel, Evan L.
AU - Forsmark, Chris E.
AU - Li, Liang
AU - Pandol, Stephen
AU - Park, Walter G.
AU - Serrano, Jose
AU - Van Den Eeden, Stephen K.
AU - Vege, Santhi Swaroop
AU - Yadav, Dhiraj
AU - Conwell, Darwin L.
AU - Cruz-Monserrate, Zobeida
N1 - Publisher Copyright:
© 2024 Lippincott Williams and Wilkins. All rights reserved.
PY - 2024
Y1 - 2024
N2 - Background: 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) like 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 CyTOF. Results: Plasma NGAL was elevated in subjects with CP compared to controls (AUC = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, BMI, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared to 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 while dihomo-γ-linolenic and adrenic acids were elevated in CP (p < 0.05). Linoleic acid was elevated in CP with diabetes compared to CP subjects without diabetes (p = 0. 0471). Conclusion: 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.
AB - Background: 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) like 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 CyTOF. Results: Plasma NGAL was elevated in subjects with CP compared to controls (AUC = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, BMI, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared to 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 while dihomo-γ-linolenic and adrenic acids were elevated in CP (p < 0.05). Linoleic acid was elevated in CP with diabetes compared to CP subjects without diabetes (p = 0. 0471). Conclusion: 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.
KW - body mass index
KW - linoleic acid
KW - lipocalin 2
KW - mass CyTOF
KW - peripheral blood mononuclear cells
KW - smoking
UR - http://www.scopus.com/inward/record.url?scp=85184938250&partnerID=8YFLogxK
U2 - 10.14309/ctg.0000000000000686
DO - 10.14309/ctg.0000000000000686
M3 - Article
C2 - 38284831
AN - SCOPUS:85184938250
SN - 2155-384X
JO - Clinical and translational gastroenterology
JF - Clinical and translational gastroenterology
ER -