Quantitative Analysis of Distribution of the Gastrointestinal Tract Eosinophils in Childhood Functional Abdominal Pain Disorders

Lee, Eun Hye; Yang, Hye Ran; Lee, Hye Seung

doi:10.5056/jnm18050

Cited by 14 publications

(23 citation statements)

References 46 publications

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“…IL-22BP levels in culture supernatants from normal and CD biopsies are consistent with the fact that eosinophils are the major source of IL-22BP in the gut. Indeed, higher levels of IL-22BP in the ileum compared to the colon is consistent with the known intestinal distribution of eosinophils 44,[51][52][53] and IL-22BP levels ae weakly but significantly correlated with eotaxins ones 44 . We found no correlation between TNF and IL-22BP as shown by Pelczar et al at the mRNA level 32 , suggesting that IL-22BP levels are not modulated by the state of inflammation.…”

Section: Discussionsupporting

confidence: 83%

IL-22BP production is heterogeneously distributed in Crohn’s disease

Fantou

Delbos²,

Abidi³

et al. 2021

Preprint

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Background & aims: IL-22 binding protein (IL-22BP) is a soluble and specific inhibitor of IL-22, a cytokine with known protective actions on intestinal epithelial cells during inflammation. Although eosinophils and mononuclear phagocytes (MNP) were shown to be the producers of IL-22BP in the intestine lamina propria (LP), it has recently been proposed that CD4+ T cells represent an additional source of IL-22BP in the gut during Crohn's disease (CD). In this study we sought to confirm these findings and to assess IL-22BP secretion levels. Methods: We investigated IL-22BP cellular sources in CD gut samples using qPCR and ELISA on FACS-sorted LP and mesenteric lymph nodes (MLN) cell subsets. We also evaluated IL-22BP levels in ex-vivo culture of intestinal biopsies. Results: MNP (HLA DR+ CD11c+ cells) and eosinophils isolated from LP CD tissues expressed IL22RA2, while the expression measured in the CD4+ and CD8+ T cells fractions was undetectable or 100-1000 times lower than in MNP. In MLN, IL22RA2 expression in T cells was either undetectable of 1000-fold lower than in MNPs without differences between naive and non-naive subsets. IL22RA2 expression was undetectable after ex vivo activation of both CD4+ and CD8+ T cells from LP or MLNs and IL-22BP was not detected in their supernatant, either activated or not. LP eosinophils appeared capable of secreting IL-22BP but not DCs likely due to in vitro activation as confirmed with monocyte-derived DCs. We also identified higher production of IL-22BP from ileum as compared to colon biopsies and demonstrated that IL-22BP levels correlated with those of eotaxins but not with TNF and IL-6. Finally, high ex vivo production of IL-22BP in mucosa biopsies from CD patients was only observed in smokers. Conclusion: We confirmed that eosinophils and MNPs are the major sources of IL-22BP in the gut during CD and found no clear evidence for IL-22BP expression by T cells. This work also provides new insights on factors regulating intestinal IL-22BP levels.

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Section: Discussionsupporting

confidence: 83%

IL-22BP production is heterogeneously distributed in Crohn’s disease

Fantou

Delbos²,

Abidi³

et al. 2021

Preprint

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“…With regard to the eosinophilic infiltration of different parts of the gastric mucosa, the reports are conflicting. Some studies have shown no differences in the eosinophilic infiltration of the gastric antrum compared to the gastric body [ 3 ], while others reported a greater eosinophilic infiltration of the gastric antrum (but not of the gastric body) in children with functional abdominal pain disorders compared to healthy controls [ 6 ]. The differences in eosinophilic counts found between the different parts of the stomach in our study were not related to the presence or not of abdominal pain, but may be considered in the context of the geographical variations that we found in all of the GI biopsies, a finding consistent with previous reports on eos concentrations in normal colonic mucosa [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, the eosinophilic density of GI tract mucosa of healthy children, which would provide baseline data for the diagnosis of EGIDs, has been poorly defined [ 2 - 5 ]. Inflammatory bowel disease has been reported to be associated with increased eosinophilic infiltration of the childhood GI tract [ 6 ], while the association of functional GI disorders (FGIDs) with increased eosinophil (eos) density of the child’s GI tract is controversial: some studies report increased eosinophilic infiltration of the GI tissue mucosa in children with FGIDs [ 7 ], whereas others do not [ 8 ]. Furthermore, the geographical variations in the distribution or density of GI tissue eos in children with no organic diseases have been poorly defined.…”

Section: Introductionmentioning

confidence: 99%

Distribution of eosinophils in the gastrointestinal tract of children with no organic disease

Koutri

Patereli

Noni

et al. 2020

aog

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Background This study aimed to assess the eosinophil (eos) density of the mucosa of the gastrointestinal (GI) tract in children undergoing endoscopic procedures following an extensive workup, without diagnosis of an organic disease. Methods Biopsies from GI endoscopies performed at 3 major children’s hospitals (Athens, Madrid and Rome), between January 2012 and June 2018, were evaluated by a single pathologist in each center. Peak eos counts were expressed /high power field and /mm 2 . Other histological abnormalities were also reported. Results A total of 111 children (median age 11 years; 48 boys) underwent upper endoscopy (333 biopsies), while 44 (median age 12; 25 boys) underwent ileocolonoscopy (262 biopsies). The median (interquartile range) eos/mm 2 were as follows: esophagus 0 (0-0); stomach 0 (0-3); duodenum 22 (13-29); ileum 29 (19-46); cecum 39 (25-71); ascending colon 24 (20-41); transverse colon 27 (21-57); descending colon 21 (13-27); sigmoid colon 22 (13-30); and rectum 10 (6-22). Geographical variations in GI tissue eos counts were found amongst the participating centers, but the causative factors need further evaluation. Functional GI disorders according to the Rome IV criteria were diagnosed in 73 children (37 boys, median age 13 years). No differences were found between children with or without functional GI disorder diagnosis, with regard to eos density in the GI tract. Conclusion The reported peak counts of GI tissue eos in children with no organic diseases provide normative values that may be useful in the evaluation of children with GI symptoms suggestive of eosinophilic GI disorders.

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“…All denied a history of abdominal pain, constipation, or diarrhea. We did not sex or age-match controls as colonic cell density does not appear to be affected by sex or age in children 49 – 51 .…”

Section: Methodsmentioning

confidence: 99%

The relationship between mucosal inflammatory cells, specific symptoms, and psychological functioning in youth with irritable bowel syndrome

Singh

Schurman

et al. 2020

Sci Rep

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Both mucosal inflammation and psychologic dysfunction have been implicated in irritable bowel syndrome (IBS). While some relationships between inflammation (mast cells and eosinophils) and depression have been reported in adults with IBS, relationships between inflammation and psychologic function have not been studied in children and adolescents. The aims of the current study were to: (1) assess densities of colonic mast cells, eosinophils, and TH17 cells in youth with IBS; and, (2) explore relationships between these cells and specific IBS symptoms and psychologic functioning. Utilizing previously obtained biopsies from the descending and rectosigmoid colons, densities were determined for mast cells, eosinophils, and TH17 cells, respectively, in 37 youth with IBS and 10 controls. In IBS patients, densities were assessed in relation to specific IBS symptoms and in relation to self-report anxiety and depression scores. In both the descending and rectosigmoid colons, densities of mast cells, eosinophils, and TH17 cells were higher in IBS patients as compared to controls. In IBS patients, rectosigmoid mast cell density was higher in those reporting pain relief with defecation. Also, in IBS patients, rectosigmoid eosinophilia was associated with higher anxiety scores and eosinophil density correlated with depression scores. In the descending colon, eosinophil and mast cell densities both correlated with depression scores. In conclusion, mucosal inflammation (mast cells and eosinophils) is associated with pain relief with defecation and with anxiety and depression in youth with IBS. Chronic or recurrent abdominal pain affects a substantial proportion of children and adolescents 1,2. The majority of youth with chronic abdominal pain will not have an identified organic disease but will report symptoms consistent with one of the functional gastrointestinal disorders (FGIDs) as defined by Rome criteria 3,4. There are four pain related FGIDs with irritable bowel syndrome (IBS) being one of the two most common 5. Rome IV, the most current version of Rome criteria, defines IBS by the presence of one of the following symptoms: pain related to defecation, pain associated with a change in stool frequency, or pain associated with a change in stool form 4. IBS is further subcategorized as IBS with predominant constipation (IBS-C), IBS with predominant diarrhea (IBS-D), mixed IBS with alternating constipation and diarrhea (IBS-M), and as unsubtyped 4,6. Among a variety of other factors, visceral hyperalgesia, inflammation and psychosocial factors have been highly implicated in the pathogenesis of IBS 7,8. Inflammatory cells which have been evaluated in IBS include mast cells, eosinophils, and lymphocytes, particularly T cells. Mast cells have been highly implicated in IBS pathogenesis in both IBS-C and IBS-D 9,10. IBS has been associated with an increase in the density of degranulating mast cells, while the density of mast cells in close proximity to enteric nerves correlates with abdominal pain severity 11 .

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Quantitative Analysis of Distribution of the Gastrointestinal Tract Eosinophils in Childhood Functional Abdominal Pain Disorders

Cited by 14 publications

References 46 publications

IL-22BP production is heterogeneously distributed in Crohn’s disease

IL-22BP production is heterogeneously distributed in Crohn’s disease

Distribution of eosinophils in the gastrointestinal tract of children with no organic disease

The relationship between mucosal inflammatory cells, specific symptoms, and psychological functioning in youth with irritable bowel syndrome

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