Dataset Information

IgG4+ cells are increased in the gastrointestinal tissue of pediatric patients with active eosinophilic gastritis and duodenitis and decrease in remission.

ABSTRACT:

Background

Recent studies have shown that IgG4 is increased in the esophageal tissue of eosinophilic esophagitis patients, including the presence of IgG4+ plasma cells.

Aims

Our aim was to determine whether IgG4 is elevated in the gastric or duodenal tissue of pediatric patients with eosinophilic gastritis or duodenitis (EoG or EoD).

Methods

This was a retrospective single center study. Pediatric patients were characterized as having active EoG, EoD, or as controls based on clinical symptoms and histologic features. Immunohistochemistry for IgG4 was performed in gastric and duodenal tissue, and peak IgG4+ cells were compared between groups and after treatment.

Results

The frequency of IgG4+ cells was significantly higher in patients with EoG and EoD compared to controls in the stomach [EoG 6.5 cells/hpf (3.6-10.9), control 0 cells/hpf (0-0.7), p<0.0001] and duodenum [EoD 7.5 cells/hpf (2.8-37), control 0.5 cells/hpf (0.3-1.3), p<0.001)] respectively, and positively correlated with eosinophil counts (stomach: r 0.74, p<0.0001; duodenum: r 0.57, p<0.0001). The amount of tissue IgG4 was significantly decreased in patients in remission but not in persistently active disease.

Conclusions

These data suggest local tissue production of IgG4 may be a universal feature of eosinophilic gastrointestinal disease that tracks with disease activity.

SUBMITTER: Quinn L

PROVIDER: S-EPMC9885790 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IgG4+ cells are increased in the gastrointestinal tissue of pediatric patients with active eosinophilic gastritis and duodenitis and decrease in remission.

Quinn Laura L Nguyen Brian B Menard-Katcher Calies C Spencer Lisa L

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 20220903 1

<h4>Background</h4>Recent studies have shown that IgG4 is increased in the esophageal tissue of eosinophilic esophagitis patients, including the presence of IgG4+ plasma cells.<h4>Aims</h4>Our aim was to determine whether IgG4 is elevated in the gastric or duodenal tissue of pediatric patients with eosinophilic gastritis or duodenitis (EoG or EoD).<h4>Methods</h4>This was a retrospective single center study. Pediatric patients were characterized as having active EoG, EoD, or as controls based on ...[more]

PMID: 36064648

Similar Datasets

Project description:BackgroundEosinophilic gastritis and duodenitis are characterized by gastrointestinal mucosal eosinophilia, chronic symptoms, impaired quality of life, and a lack of adequate treatments. Mast-cell activity may contribute to the pathogenesis of the conditions. AK002 (lirentelimab) is an anti-Siglec-8 antibody that depletes eosinophils and inhibits mast cells and that has shown potential in animal models as a treatment for eosinophilic gastritis and duodenitis.MethodsIn this phase 2 trial, we randomly assigned adults who had symptomatic eosinophilic gastritis, eosinophilic duodenitis, or both conditions in a 1:1:1 ratio to receive four monthly infusions of low-dose AK002, high-dose AK002, or placebo. The primary end point was the change in gastrointestinal eosinophil count from baseline to 2 weeks after the final dose; to maximize statistical power, we evaluated this end point in the placebo group as compared with the combined AK002 group. Secondary end points were treatment response (>30% reduction in total symptom score and >75% reduction in gastrointestinal eosinophil count) and the change in total symptom score.ResultsOf the 65 patients who underwent randomization, 43 were assigned to receive AK002 and 22 were assigned to receive placebo. The mean percentage change in gastrointestinal eosinophil count was -86% in the combined AK002 group, as compared with 9% in the placebo group (least-squares mean difference, -98 percentage points; 95% confidence interval [CI], -121 to -76; P<0.001). Treatment response occurred in 63% of the patients who received AK002 and in 5% of the patients who received placebo (difference, 58 percentage points; 95% CI, 36 to 74; P<0.001). The mean change in total symptom score was -48% with AK002 and -22% with placebo (least-squares mean difference, -26 percentage points; 95% CI, -44 to -9; P = 0.004). Adverse events associated with AK002 were similar to those with placebo, with the exception of higher percentages of patients having mild-to-moderate infusion-related reactions with AK002 (60% in the combined AK002 group and 23% in the placebo group).ConclusionsIn patients with eosinophilic gastritis or duodenitis, AK002 reduced gastrointestinal eosinophils and symptoms. Infusion-related reactions were more common with AK002 than with placebo. (Funded by Allakos; ENIGMA ClinicalTrials.gov number, NCT03496571.).

Project description:Background & aimsEosinophilic gastritis (EG) and eosinophilic duodenitis (EoD), characterized by chronic gastrointestinal (GI) symptoms and increased numbers or activation of eosinophils and mast cells in the GI tract, are likely underdiagnosed. We aimed to determine rates of EG and EoD and number of biopsies required to optimize detection using screening data from a randomized trial of lirentelimab (AK002), an antibody against siglec-8 that depletes eosinophils and inhibits mast cells. We also characterized endoscopic features and symptoms of EG and EoD.MethodsSubjects with moderate-to-severe GI symptoms, assessed daily through a validated patient-reported outcome questionnaire, underwent endoscopy with a systematic gastric and duodenal biopsy protocol and histopathologic evaluation. EG diagnosis required presence of ≥30 eosinophils/high-power field (eos/hpf) in ≥5 hpfs and EoD required ≥30 eos/hpf in ≥3 hpfs. We analyzed diagnostic yields for EG and EoD and histologic, endoscopic, and clinical findings.ResultsOf 88 subjects meeting symptom criteria, 72 were found to have EG and/or EoD (EG/EoD), including patients with no prior diagnosis of EG/EoD. We found that GI eosinophilia was patchy and that examination of multiple biopsies was required for diagnosis-an average of only 2.6 per 8 gastric biopsies and 2.2 per 4 duodenal biopsies per subject met thresholds for EG/EoD. Evaluation of multiple nonoverlapping hpfs in each of 8 gastric and 4 duodenal biopsies was required to capture 100% of EG/EoD cases. Neither endoscopic findings nor symptom severity correlated with eosinophil counts.ConclusionsIn an analysis of patients with moderate-to-severe GI symptoms participating in a clinical trial of lirentelimab for EG/EoD, we found eosinophilia to be patchy in gastric and duodenal biopsies. Counting eosinophils in at least 8 gastric and 4 duodenal biopsies is required to identify patients with EG/EoD, so they can receive appropriate treatment. (ClinicalTrials.gov, Number: NCT03496571).

Dataset Information

IgG4+ cells are increased in the gastrointestinal tissue of pediatric patients with active eosinophilic gastritis and duodenitis and decrease in remission.

Background

Aims

Methods

Results

Conclusions

Publications

IgG4+ cells are increased in the gastrointestinal tissue of pediatric patients with active eosinophilic gastritis and duodenitis and decrease in remission.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets