Pancreatitis-Associated Protein Does Not Predict Disease Relapse in Inflammatory Bowel Disease Patients

Tiago Nunes,Susana Pinó Donnay,Mathias Chamaillard,Teddy Grandjean,Juan Lucio Iovanna,Maria Jose Sandi,Elena Ricart,Miquel Sans,Maria Pellisé,Maria Josefina Etchevers,Jean-Charles Dagorn,Julián Panés,Simon Patrick Hogan

doi:10.1371/journal.pone.0084957

Abstract

BackgroundThe pancreatitis-associated protein (PAP) is increased in the serum of active inflammatory bowel disease (IBD) patients and its levels seem to be correlated with disease activity. Our aim was to evaluate the usefulness of serum and fecal PAP measurements to predict relapse in patients with inactive IBD.Materials and MethodsWe undertook a 12-month prospective study that included 66 Crohn's disease (CD) and 74 ulcerative colitis (UC) patients. At inclusion, patients were in clinical remission, defined by a Harvey-Bradshaw (HB) Index≤4 (CD) or a partial Mayo Score (MS)<3 (UC), along with a normal serum C reactive protein (CRP) and fecal calprotectin. Patients were followed every 3 months. Blood and stool samples were collected and a clinical evaluation was performed at each visit. Serum PAP and CRP levels as well as fecal concentrations of PAP and calprotectin were assessed.ResultsActive CD patients had an increased mean serum PAP at the diagnosis of the flare (104.1 ng/ml) and 3 months prior to activity (22.68 ng/ml) compared with patients in remission (13.26 ng/ml), p<0.05. No significant change in serum PAP levels in UC and fecal PAP levels in CD and UC were detected during disease activity. In CD, serum PAP was a poor diagnostic predictor of disease activity, with an AUC of 0.69. In patients in remission, fecal PAP was barely detectable in UC compared with CD patients.ConclusionSerum PAP is increased only in active CD patients, but this marker does not predict disease activity. Inactive UC patients have marked low levels of PAP in fecal samples compared with CD patients.

Highlights

The pancreatitis-associated protein (PAP), known as regenerating islet-derived protein 3 b (Reg3b) in mice, is a soluble calcium-dependent carbohydrate-binding protein which is expressed by intestinal epithelial cells.[1]
No significant change in serum PAP levels in ulcerative colitis (UC) and fecal PAP levels in Crohn’s disease (CD) and UC were detected during disease activity
Fecal PAP was barely detectable in UC compared with CD patients

Summary

Introduction

The pancreatitis-associated protein (PAP), known as regenerating islet-derived protein 3 b (Reg3b) in mice, is a soluble calcium-dependent carbohydrate-binding protein which is expressed by intestinal epithelial cells.[1] It has been shown that colonization of germ-free mice with pathogens increases the expression PAP/Reg3b in the murine ileum and that this protein is directly bactericidal for gram-positive bacteria.[1] PAP/Reg3b plays a protective role against intestinal translocation of gramnegative bacteria probably through interference with virulence mechanisms or host responses to these pathogens.[1] PAP/Reg3b triggers bacterial aggregation and displays bactericidal activity through its ability to directly bind some carbohydrate components of peptidoglycan.[2,3] Recently, a protective role has been proposed for PAP/Reg3b in liver and pancreas, which is apparently independent of its bactericidal properties.[4,5] In vitro studies showed that this protein plays an essential role in the negative regulation of cytokine signaling.[6,7]. The pancreatitis-associated protein (PAP) is increased in the serum of active inflammatory bowel disease (IBD) patients and its levels seem to be correlated with disease activity.

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