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

Abstract

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.