Abstract

BackgroundDiscriminating between autoimmune pancreatitis (AIP), chronic pancreatitis (CP), and pancreatic ductal adenocarcinoma (PDAC) can be challenging. In this retrospective study, levels of serum and tissue cytokines were analyzed as part of the clinical strategy for the preoperative differentiation between AIP and PDAC. The identification of differential cytokine profiles may help to prevent unnecessary surgical resection and allow optimal treatment of these pathologies.MethodsTo compare the cytokine profiles of AIP, CP, and PDAC patients, serum and pancreatic tissue homogenates were subjected to multiplex analysis of 17 inflammatory mediators. In total, serum from 73 patients, composed of 29 AIP (14 AIP-1 and 15 AIP-2), 17 CP, and 27 PDAC, and pancreatic tissue from 36 patients, including 12 AIP (six AIP-1 and six AIP-2), 12 CP, and 12 PDAC, were analyzed.ResultsComparing AIP and PDAC patients’ serum, significantly higher concentrations were found in AIP for interleukins IL-1β, IL-7, IL-13, and granulocyte colony-stimulating factor (G-CSF). G-CSF also allowed discrimination of AIP from CP. Furthermore, once AIP was divided into subtypes, significantly higher serum levels for IL-7 and G-CSF were measured in both subtypes of AIP and in AIP-2 for IL-1β when compared to PDAC. G-CSF and TNF-α were also significantly differentially expressed in tissue homogenates between AIP-2 and PDAC.ConclusionsThe cytokines IL-1β, IL-7, and G-CSF can be routinely measured in patients’ serum, providing an elegant and non-invasive approach for differential diagnosis. G-CSF is a good candidate to supplement the currently known serum markers in predictive tests for AIP and represents a basis for a combined blood test to differentiate AIP and particularly AIP-2 from PDAC, enhancing the possibility of appropriate treatment.

Highlights

  • Discriminating between autoimmune pancreatitis (AIP), chronic pancreatitis (CP), and pancreatic ductal adenocarcinoma (PDAC) can be challenging

  • Comparisons were performed among the AIP type 1 (AIP-1), AIP type 2 (AIP-2), PDAC, and CP groups using AIP-1 and AIP-2 separately as reference categories

  • When AIP-1, AIP-2, CP, and PDAC were compared and AIP-1 was used as a reference category, significantly higher concentrations of IL-7 (p = 0.0012), IL-13 (p = 0.0162), and granulocyte colony-stimulating factor (G-CSF) (p = 0.0425) were found in AIP-1 compared to PDAC

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Summary

Introduction

Discriminating between autoimmune pancreatitis (AIP), chronic pancreatitis (CP), and pancreatic ductal adenocarcinoma (PDAC) can be challenging In this retrospective study, levels of serum and tissue cytokines were analyzed as part of the clinical strategy for the preoperative differentiation between AIP and PDAC. AIP type 2 (AIP-2), called idiopathic duct-centric pancreatitis (IDCP), is recognized by its specific histological feature: granulocytic epithelial lesions (GEL) [1, 2, 6, 12] These lesions consist of a focal disruption and destruction of the duct epithelium caused by the invasion of neutrophilic granulocytes, which makes some people call it AIP with GEL. It is likely that deregulated cytokines and other transcription factors are the driving force by which neutrophils are recruited to the ductal and acinar cells with subsequent destruction This latter subtype is more common in Western countries [5]

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