Fecal Lactoferrin and Other Putative Fecal Biomarkers in Crohn’s Disease: Do They Still Have a Potential Clinical Role?

Vernia, Filippo; Ruscio, Mirko Di; Stefanelli, Gianpiero; Valvano, Marco; Latella, Giovanni

doi:10.1159/000518419

Cited by 9 publications

(6 citation statements)

References 81 publications

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“…3–5,16 Biomarkers are prime candidate tools to that end. However, concerning neutrophil-related biomarkers, the focus has been on fecal molecules, 10,55 which present well-known convenience limitations. 14 Indeed, of the 119 neutrophil, but non-blood-related excluded entries, 89 studied fecal compounds.…”

Section: Discussionmentioning

confidence: 99%

“…1,6,7 In fact, fecal calprotectin (FC) is a neutrophil-related biomarker widely used to monitor disease 8 and is recommended as a target of treatment. 9 A multitude of other biomarkers, especially fecal, 10 have been extensively studied, but with primary focus on differential diagnosis or disease activity monitoring. 11,12 In contrast, predictive biomarkers provide information on the anticipated response to a specific treatment intervention.…”

Section: Introductionmentioning

confidence: 99%

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Pursuing neutrophils: systematic scoping review on blood-based biomarkers as predictors of treatment outcomes in inflammatory bowel disease

Magalhães

Peyrin–Biroulet

Estevinho

et al. 2023

Therap Adv Gastroenterol

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Background: Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need. Neutrophil-related biomarkers have been mainly studied in the feces, but blood analyses have inherent advantages. Objective: To review the recent learnings on the ability of blood-based neutrophil-expressed biomarkers to predict treatment outcomes in IBD. Design: Systematic scoping review. Data sources and methods: We performed a literature search in Pubmed, EMBASE, SCOPUS, Web of Science, ScienceDirect, and Cochrane Central Register of Controlled Trials from inception until May 2022 according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. All human studies associating blood-based neutrophil-related compounds with the prediction of disease progression, complication onset, or treatment outcomes were included. Results: From 1032 retrieved entries, 34 studies were selected, 32 published in 2013 or later. In all, 17 biomarkers from granules, cytoplasm, plasmatic membrane, and plasma were explored. In total, 1850 Crohn’s disease (CD) and 1122 ulcerative colitis non-duplicated patients were included. The most mentioned biomarkers were nCD64, serum calprotectin (SC), oncostatin M (OSM), neutrophil elastase-generated calprotectin fragment (CPa9-HNE), and triggering receptor expressed on myeloid cells 1 (TREM1). Six biomarkers showed promising results: OSM, SC, eNAMPT, nCD64, TREM1, and CPa9-HNE. Variable positive signals were found for human neutrophil peptide 1-3, LL-37, S100A12, and neutrophil gelatinase–associated lipocalin. No predictive ability was found for the remaining markers. Sharing a neutrophil compartment did not indicate similar behavior. Conclusion: Advances in the last decade began to unveil the untapped potential of the readily accessible blood neutrophil-expressed biomarkers, especially nCD64, TREM1, and CPa9-HNE. Current evidence suggests that future research should focus on well-defined subpopulations instead of a one-size-fits-all biomarker. Registration: https://osf.io/kes9a .

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pursuing neutrophils: systematic scoping review on blood-based biomarkers as predictors of treatment outcomes in inflammatory bowel disease

Magalhães

Peyrin–Biroulet

Estevinho

et al. 2023

Therap Adv Gastroenterol

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“…Faecal calprotectin is an established biomarker in IBD ( 33 ) and MMP-9 and lipocalin (NGAL) are being studied as surrogate markers for calprotectin ( 34 ). These molecules, as well as lactoferrin ( 35 ) and others are major products of neutrophils. For this reason, the presence of molecules in the faeces may be surrogate markers of neutrophils entering the intestinal lumen, where they disintegrate ( vide infra ).…”

Section: Biomarkers and Mmp-based Surrogate Markers For Ibdmentioning

confidence: 99%

How to place the duality of specific MMP-9 inhibition for treatment of inflammatory bowel diseases into clinical opportunities?

2022

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Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) with the involvement of immune cells and molecules, including cytokines, chemokines and proteases. A previous extensive review about the molecular biology of matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs), related to intestinal barrier destruction and restoration functions in IBD, is here complemented with the literature from the last five years. We also compare IBD as a prototypic mucosal inflammation of an epithelial barrier against microorganisms with inflammatory retinopathy as a disease with a barrier dysfunction at the level of blood vessels. Multiple reasons are at the basis of halting clinical trials with monoclonal antibodies against MMP-9 for IBD treatment. These include (i) the absence of a causative role of MMP-9 in the pathology in animal models of IBD, (ii) the fact that endotoxins, crossing the intestinal barrier, induce massive local release of both neutrophil collagenase (MMP-8) and gelatinase B (MMP-9), (iii) insufficient recognition that MMPs modify the activities of cytokines, chemokines and their receptors, (iv) ignorance that MMPs exist as mixtures of proteoforms with different posttranslational modifications and with different specific activities and (v) the fact that MMPs and TIMPs act in an interactive network, possibly having also beneficial effects on IBD evolution. Nevertheless, inhibition of MMPs may be a useful therapeutic approach during specific IBD disease phases or in specific sub-phenotypes. This temporary “window of opportunity” for MMP-9 inhibition may be complemented by a locoregional one, provided that the pharmacological agents are targeted in time to affected tissues, as is achieved in ophthalmological inflammation. Thus, in order to discover spatial and temporal windows of opportunity for MMP inhibition as treatment of IBD, more preclinical work including well controlled animal studies will be further needed. In this respect, MMP-9/NGAL complex analysis in various body compartments is helpful for better stratification of IBD patients who may benefit from anti-MMP-9.

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“…It has not been studied as widely as calprotectin, and whether it has any additional benefit is currently unkown. 33…”

Section: Pediatric Inflammatory Bowel Diseasementioning

confidence: 99%

Pediatric Inflammatory Bowel Disease

Bouhuys¹,

Lexmond²,

Rheenen³

2022

Pediatrics

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Inflammatory bowel diseases (IBDs) are chronic, immune-mediated disorders that include Crohn’s disease and ulcerative colitis. A pediatric onset of disease occurs in about 10% of all cases. Clinical presentation of IBD with rectal bleeding or perianal disease warrants direct referral for endoscopic evaluation. In the absence of red-flag symptoms, a combination of patient history and blood and fecal biomarkers can help to distinguish suspected IBD from other causes of abdominal pain or diarrhea. The therapeutic management of pediatric IBD has evolved by taking into account predictors of poor outcome, which justifies the upfront use of anti-tumor necrosis factor therapy for patients at high risk for complicated disease. In treating patients with IBD, biochemical or endoscopic remission, rather than clinical remission, is the therapeutic goal because intestinal inflammation often persists despite resolution of abdominal symptoms. Pediatric IBD comes with unique additional challenges, such as growth impairment, pubertal delay, the psychology of adolescence, and development of body image. Even after remission has been achieved, many patients with IBD continue to experience nonspecific symptoms like abdominal pain and fatigue. Transfer to adult care is a well-recognized risk for disease relapse, which highlights patient vulnerability and the need for a transition program that is continued by the adult-oriented IBD team. The general pediatrician is an invaluable link in integrating these challenges in the clinical care of patients with IBD and optimizing their outcomes. This state-of-the-art review aims to provide general pediatricians with an update on pediatric IBD to facilitate interactions with pediatric gastrointestinal specialists.

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Fecal Lactoferrin and Other Putative Fecal Biomarkers in Crohn’s Disease: Do They Still Have a Potential Clinical Role?

Cited by 9 publications

References 81 publications

Pursuing neutrophils: systematic scoping review on blood-based biomarkers as predictors of treatment outcomes in inflammatory bowel disease

Pursuing neutrophils: systematic scoping review on blood-based biomarkers as predictors of treatment outcomes in inflammatory bowel disease

How to place the duality of specific MMP-9 inhibition for treatment of inflammatory bowel diseases into clinical opportunities?

Pediatric Inflammatory Bowel Disease

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