LAUSR

BACKGROUND AND AIMS Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and, in some cases, progressing 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 aimed to examine whether patient serum immune profiling could identify non-invasive 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 PROCEED study of the CPDPC consortium. Samples (n=231) were obtained from subjects without the pancreatic disease (n=56) and those with chronic abdominal pain (CAP) (n=24), AP (n=38), RAP (n=56), and CP (n=57). RESULTS Thirty-three immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to IL-17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL-17A and CCL20 differentiated CP from CAP, suggesting the involvement of Th17 cells in CP pathogenesis. The receiver operator characteristic (ROC) curve with two immune markers (IL-17A and ST1A1) could differentiate CP from CAP (optimistic AUC=0.78). 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. CONCLUSION 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 IL-17 signaling in CP could provide insight into the immune mechanisms underlying disease progression.