Current and emerging biomarkers in the management of inflammatory bowel disease

Xia & He Publishing Inc.Sep 12 2024

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal (GI) tract that significantly impacts the quality of life of patients. With an incidence of approximately one in 200 individuals in developed countries and a rising trend in developing and newly industrialized nations, IBD poses a substantial burden on healthcare systems. Due to the nonspecific nature of its clinical manifestations and the lack of a gold-standard diagnostic test, managing IBD effectively remains a challenge. Therefore, reliable and widely available biomarkers for monitoring disease activity and predicting treatment response are essential.

This review comprehensively examines the current landscape of biomarkers used in IBD management. The authors focus on both established and novel biomarkers, emphasizing their uses, threshold values, and clinical considerations.

Established biomarkers

C-reactive protein (CRP): CRP is one of the most widely used biomarkers for monitoring IBD activity due to its low cost, ease of testing, and well-established protocols. It is an acute-phase reactant produced by hepatocytes in response to pro-inflammatory cytokines. However, its diagnostic value is limited by a lack of specificity, as elevations can also be caused by other inflammatory conditions. CRP is particularly useful in CD, where it correlates with moderate to severe clinical activity and evidence of active disease on ileocolonoscopy. In UC, the correlation is less clear, and normal CRP levels do not necessarily rule out active disease. Recent guidelines recommend monitoring CRP alongside fecal calprotectin in asymptomatic patients to avoid more invasive and costly testing.

Erythrocyte sedimentation rate (ESR): ESR is another commonly tested marker of inflammation, though it lacks specificity similar to CRP. It differs from CRP in its slower response to inflammation and longer normalization time. ESR can be affected by physiological factors such as pregnancy, age, and gender, as well as medication use, highlighting the importance of interpreting results in context.

Vitamin D: Vitamin D deficiency is prevalent in IBD patients and is associated with increased risk of disease recurrence, hospitalizations, and surgeries. Its role as an immune modulator suggests therapeutic potential, though further research is needed to determine optimal supplementation levels and therapeutic benefits.

Platelets: Platelets, often overlooked in IBD evaluations, play an active role in inflammatory processes. Reactive thrombocytosis, a well-established phenomenon in inflammation, has been observed in IBD patients, with platelets exhibiting increased sensitivity to activation even in clinically silent disease. Platelet changes may correlate with disease relapse in UC.

Novel biomarkers

Recent studies have focused on developing novel biomarkers with improved specificity and predictive value for IBD management. Examples include:

Mucosal addressin cell-adhesion molecule-1 (MAdCAM-1): Elevated levels of MAdCAM-1 have been associated with inflammation and may predict response to vedolizumab, a monoclonal antibody used in IBD treatment.

Oncostatin M: Elevated oncostatin M levels could predict the risk of IBD development and potentially nonresponse to vedolizumab or corticosteroids.

NOD2 mutations: Genetic analysis for NOD2 mutations may be predictive of fibrostenotic disease in CD, though it is not specific for treatment response.

Anti-Integrin αvβ6: Blood levels of anti-Integrin αvβ6 are useful for diagnosing and predicting disease severity in UC, though they do not specifically predict treatment response.

Conclusions

In conclusion, the review highlights the crucial role of biomarkers in the management of IBD. While established biomarkers such as CRP, ESR, vitamin D, and platelets continue to play a vital role, novel biomarkers offer promise for improving diagnostic accuracy and predicting treatment response. Future research should focus on developing more sensitive and specific biomarkers that can guide personalized treatment plans, ultimately leading to better outcomes for IBD patients. The combination of established and novel biomarkers in biomarker panels and ratios may hold the key to more efficient and effective IBD management in the years to come.