Novel fibro-inflammatory biomarkers associated with disease activity in patients with Crohn’s disease

ABSTRACT

Introduction

Crohn’s disease (CD) is a complex disease, and assessing activity is challenging due to pathobiologic process e.g. ECM remodeling, mucosal damage, and intestinal fibrosis, which greatly limits current disease activity assessments through e.g. endoscopy and imaging techniques.

Areas covered

The review highlights the importance of novel biomarkers reflecting ECM remodeling and immune cell activity that accurately reflect CD activity and progression. Such biomarkers could include collagen formation and degradation fragments and a serum fragment of calprotectin, reflecting neutrophil activity. A new concept, fibro-inflammation, is also introduced in the review, in which all aspects of mucosal damage, such as inflammation, mucosal damage, tissue remodeling, intestinal fibrosis, and fibrosis resolution, should be assessed. PubMed searches performed from July 2022 – November 2022 provided the scientific information included in the review.

Expert opinion

Current data suggest intestinal fibrosis may sustain and exacerbate chronic inflammation, leading to non-response to anti-inflammatory treatments. Therefore, evaluating novel biomarkers reflecting different stages of fibro-inflammatory disease activity should be done in a clinical setting and considered for clinical trials. This approach will help accurately assess disease activity, leading to better management and treatment of CD.

KEYWORDS:

• Biomarkers
• disease activity
• Crohn’s disease
• protein fingerprint
• proximity extension assay
• aptamers
• fibro-inflammation
• serum calprotectin

Article highlights

• With a paradigm shift in treatment goals, including mucosal and transmural healing, the requirement for novel biomarkers is increasing. Implementing objective serological biomarkers capable of assessing submucosal processes could provide accurate molecular patient stratification and disease assessment.

• The concept of fibro-inflammation, encompassing inflammation, mucosal damage, fibrogenesis, and fibrosis resolution, should be considered for an enhanced understanding of the pathobiology of Crohn’s disease

• Protein fingerprint assays assessing ECM remodeling and neutrophil activity are candidate biomarkers for accurately evaluating disease activity, treatment efficacy, and fibro-inflammation in patients with Crohn’s disease.

• Proximity extension and aptamer-based assays allow for high-throughput proteomics to be used as a discovery tool for more specialized biomarkers by evaluating thousands of proteins, though the exact applicability requires more extensive validated studies.

• With no qualified regulatory approved biomarkers for Crohn’s disease, understanding the regulatory process of these novel biomarkers will be a crucial element in the further progression of the novel biomarkers presented in this review.

• Biomarkers reflecting the fibro-inflammatory axis can be applied to accelerate the development of novel and effective therapeutics (anti-inflammatory and anti-fibrotic), advancing precision medicine.

Declaration of interest

The following authors are fulltime employees at Nordic Bioscience A/S: M Pehrsson, M Sorokina Alexdottir, M Asser Karsdal, and J Høg Mortensen. M Pehrsson, M Asser Karsdal, and J Høg Mortensen are stock holders in Nordic Bioscience A/S – A Company dedicated to the Discovery and Development of biomarkers. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.