Inflammatory bowel disease detection and monitoring by measuring biomarkers in non‐invasively collected colorectal mucus

Loktionov, Alexandre; Chhaya, Vivek; Bandaletova, Tatiana; Poullis, Andrew

doi:10.1111/jgh.13627

Cited by 16 publications

(20 citation statements)

References 53 publications

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“…Studies of our group convincingly demonstrated the abundance of inflammatory cells, predominantly neutrophils, in colorectal mucus collected from IBD patients either intrarectally[190,191] or non-invasively[192,193]. Common eosinophil presence in this material was also noted[191,193], especially in UC patients[193], and dramatically increased EDN levels were determined[191,194], typically with higher values in UC compared to CD[194]. Detailed cytological analysis of these samples demonstrated that colorectal mucus from patients with active IBD commonly contains not only huge amounts of neutrophils, but also eosinophils, macrophages, erythrocytes as well as occasional plasma cells, lymphocytes and basophils[193].…”

Section: Eosinophil Impact In the Pathogenesis Of Major Colorectal DImentioning

confidence: 80%

“…On the other hand, it should not be forgotten that transepithelial migration of immune cells is a major factor in mucosal disease resolution, as demonstrated for airway diseases[204,205]. Indeed, the presence of both inflammatory cells and biomarkers associated with them significantly decreased in colorectal mucus samples from successfully treated IBD patients[194]. It is, therefore, probable that gradual distal movement of colorectal mucus[189] creates favourable conditions for eliminating dead or obsolete immune cells from the surface of colonic epithelium if inflammation is successfully resolved.…”

Section: Eosinophil Impact In the Pathogenesis Of Major Colorectal DImentioning

confidence: 99%

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Eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders

Loktionov

2019

WJG

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Eosinophils are currently regarded as versatile mobile cells controlling and regulating multiple biological pathways and responses in health and disease. These cells store in their specific granules numerous biologically active substances (cytotoxic cationic proteins, cytokines, growth factors, chemokines, enzymes) ready for rapid release. The human gut is the main destination of eosinophils that are produced and matured in the bone marrow and then transferred to target tissues through the circulation. In health the most important functions of gut-residing eosinophils comprise their participation in the maintenance of the protective mucosal barrier and interactions with other immune cells in providing immunity to microbiota of the gut lumen. Eosinophils are closely involved in the development of inflammatory bowel disease (IBD), when their cytotoxic granule proteins cause damage to host tissues. However, their roles in Crohn’s disease and ulcerative colitis appear to follow different immune response patterns. Eosinophils in IBD are especially important in altering the structure and protective functions of the mucosal barrier and modulating massive neutrophil influx to the lamina propria followed by transepithelial migration to colorectal mucus. IBD-associated inflammatory process involving eosinophils then appears to expand to the mucus overlaying the internal gut surface. The author hypothesises that immune responses within colorectal mucus as well as ETosis exerted by both neutrophils and eosinophils on the both sides of the colonic epithelial barrier act as additional pathogenetic factors in IBD. Literature analysis also shows an association between elevated eosinophil levels and better colorectal cancer (CRC) prognosis, but mechanisms behind this effect remain to be elucidated. In conclusion, the author emphasises the importance of investigating colorectal mucus in IBD and CRC patients as a previously unexplored milieu of disease-related inflammatory responses.

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Section: Eosinophil Impact In the Pathogenesis Of Major Colorectal DImentioning

confidence: 80%

Section: Eosinophil Impact In the Pathogenesis Of Major Colorectal DImentioning

confidence: 99%

Eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders

Loktionov

2019

WJG

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“…Studies in patients with different forms of GI eosinophilic inflammation have shown increased numbers of activated eosinophils and increased concentrations of extracellular granule protein, suggesting that these cells may be important players in promoting and mediating inflammation in the intestinal mucosa 29, 30, 31, 32. Therefore, it is important to be able to reliably detect and quantify both intact and degranulated eosinophils in order to better understand their involvement and contribution to disease pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Assessment of eosinophils in gastrointestinal inflammatory disease of dogs

Baştan

Seelig

Day

et al. 2018

Veterinary Internal Medicne

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BackgroundAccurate identification of eosinophils in the gastrointestinal (GI) tract of dogs with eosinophilic GI disease (EGID) by histological evaluation is challenging. The currently used hematoxylin and eosin (H&E) staining method detects intact eosinophils but does not detect degranulated eosinophils, thus potentially underrepresenting the number of infiltrating eosinophils.ObjectiveTo develop a more sensitive method for identifying and quantifying both intact and degranulated eosinophils to diagnose EGID more accurately.MethodsEndoscopically obtained paraffin‐embedded intestinal biopsy specimens from dogs with GI signs were examined. The study groups were dogs with eosinophilic enteritis (EE), lymphoplasmacytic and mixed enteritis, and control dogs with GI signs but no histologic changes on tissue sections. Consecutive sections were immunolabeled with monoclonal antibodies (mAbs) against the eosinophil granule protein eosinophil peroxidase (Epx) and stained by H&E, respectively. The number of eosinophils was manually quantified and classified as intact or degranulated.ResultsThe number of intact eosinophils detected in Epx mAb‐labeled duodenal sections was significantly higher compared with that in H&E‐stained sections, with a similar relationship noted in the colon and stomach. The Epx mAb allowed the unique assessment of eosinophil degranulation. The number of intact and degranulated eosinophils was significantly higher in duodenal lamina propria of the EE and mixed group compared to the control group.ConclusionImmunohistochemical detection of Epx provides a more precise method to detect GI tract eosinophils compared to H&E staining and could be used as an alternative and reliable diagnostic tool for assessment of biopsy tissues from dogs with EGID.

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“…Finally, colorectal mucus could be further explored as a potential sample source. Previous studies have established that colorectal mucus is a rich source of potential IBD biomarkers, as demonstrated by the quantification of calprotectin and eosinophil-derived neurotoxin in mucus samples from IBD patients [ 110 , 111 ].…”

Section: Proteomics and Lipidomics In Ibd Research—going Forwardmentioning

confidence: 99%

Proteomics and Lipidomics in Inflammatory Bowel Disease Research: From Mechanistic Insights to Biomarker Identification

Titz

Gadaleta

Sasso

et al. 2018

IJMS

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Inflammatory bowel disease (IBD) represents a group of progressive disorders characterized by recurrent chronic inflammation of the gut. Ulcerative colitis and Crohn′s disease are the major manifestations of IBD. While our understanding of IBD has progressed in recent years, its etiology is far from being fully understood, resulting in suboptimal treatment options. Complementing other biological endpoints, bioanalytical “omics” methods that quantify many biomolecules simultaneously have great potential in the dissection of the complex pathogenesis of IBD. In this review, we focus on the rapidly evolving proteomics and lipidomics technologies and their broad applicability to IBD studies; these range from investigations of immune-regulatory mechanisms and biomarker discovery to studies dissecting host–microbiome interactions and the role of intestinal epithelial cells. Future studies can leverage recent advances, including improved analytical methodologies, additional relevant sample types, and integrative multi-omics analyses. Proteomics and lipidomics could effectively accelerate the development of novel targeted treatments and the discovery of complementary biomarkers, enabling continuous monitoring of the treatment response of individual patients; this may allow further refinement of treatment and, ultimately, facilitate a personalized medicine approach to IBD.

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Inflammatory bowel disease detection and monitoring by measuring biomarkers in non‐invasively collected colorectal mucus

Cited by 16 publications

References 53 publications

Eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders

Eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders

Assessment of eosinophils in gastrointestinal inflammatory disease of dogs

Proteomics and Lipidomics in Inflammatory Bowel Disease Research: From Mechanistic Insights to Biomarker Identification

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