Maria Ling Lundström: Faecal biomarkers of neutrophil and eosinophil origin in the evaluation of inflammatory bowel disease: Providing insights into the patophysiology

Abstract

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is characterised by chronic inflammation of the gastrointestinal tract. The gold standard for diagnosing and monitoring IBD is by endoscopy, but biomarkers, like the clinically established faecal calprotectin (FC), can function as non-invasive surrogate markers reflecting disease activity. As FC has some known limitations, it is worthwhile to investigate the performance of alternative faecal markers. Therefore, we aimed to evaluate eosinophil and neutrophil granule proteins as potential faecal biomarkers for different aspects of IBD. An additional aim was to study the association of eosinophils with IBD onset.

In Paper I, we explored the role of eosinophils in the pathophysiology of IBD by studying faecal eosinophil markers in a cohort of discordant twin pairs. This study showed that, unlike neutrophils, eosinophils are not active in the pre-clinical state of IBD. Thus, activation of eosinophils is a consequence of inflammation rather than a primary event triggering the onset of disease. In Paper II, the diagnostic association and predictive performance of neutrophil and eosinophil faecal markers were evaluated in a cohort of newly-onset IBD patients. We showed that Myeloperoxidase (MPO) and FC have comparable diagnostic capacities in IBD and that combining FC and MPO could enhance diagnostic accuracy. We also demonstrated that neutrophil markers were predictive of an aggressive disease course in UC. Paper III showed that faecal MPO, human neutrophil lipocalin (HNL) and eosinophil-derived neurotoxin (EDN) – similar to FC – are functioning biomarkers for monitoring clinical remission in IBD patients treated with biologics. The study also demonstrated that faecal EDN and HNL are influenced by corticosteroids, indicating a response mechanism different from that of FC and MPO. In Paper IV we proposed that faecal HNL, reflecting both intestinal neutrophils and epithelial cells, can differentiate patients with gastroenteritis (GE) from new-onset IBD patients.

This comprehensive exploration of faecal biomarkers suggests interesting alternatives or adjuncts to FC in the diagnostics, monitoring and prediction of disease course in IBD. By studying these biomarkers, we have also uncovered parts of the IBD pathophysiology and increased the knowledge of the eosinophils in the early state of IBD.