Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study.

Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need among patients with EG for more precise diagnostic tools. We aimed to develop tissue- and blood-based diagnostic platforms for EG. Patients with EG and control subjects without EG were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers-associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. EGDP18 scores were derived from the expression of 18 highly dysregulated genes, and blood EG scores were derived from dysregulated cytokine/chemokine levels. Gastric biopsy specimens and blood samples from 185 subjects (patients with EG, n = 74; control subjects without EG, n = 111) were analyzed. The EGDP (1) identified patients with active EG (P < .0001, area under the curve ≥ 0.95), (2) effectively monitored disease activity in longitudinal samples (P = .0078), (3) highly correlated in same-patient samples (antrum vs body, r = 0.85, P < .0001), and (4) inversely correlated with gastric peak eosinophil levels (r = -0.83, P < .0001), periglandular circumferential collars (r = -0.73, P < .0001), and endoscopic nodularity (r = -0.45, P < .0001). For blood-based platforms, eotaxin-3, thymus and activation-regulated chemokine, IL-5, and thymic stromal lymphopoietin levels were significantly increased. Blood EG scores (1) distinguished patients with EG from control subjects without EG (P < .0001, area under the curve ≥ 0.91), (2) correlated with gastric eosinophil levels (plasma: r = 0.72, P = .0002; serum: r = 0.54, P = .0015), and (3) inversely correlated with EGDP18 scores (plasma: r = -0.64, P = .0015; serum: r = -0.46, P = .0084). Plasma eotaxin-3 levels strongly associated with gastric CCL26 expression (r = 0.81, P < .0001). We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and clinical readiness tools for this emerging rare disease.

Shoda T ，Wen T ，Caldwell JM ，Collins MH ，Besse JA ，Osswald GA ，Abonia JP ，Arva NC ，Atkins D ，Capocelli KE ，Dellon ES ，Falk GW ，Gonsalves N ，Gupta SK ，Hirano I ，Mukkada VA ，Putnam PE ，Sheridan RM ，Rudman Spergel AK ，Spergel JM ，Wechsler JB ，Yang GY ，Aceves SS ，Furuta GT ，Rothenberg ME ，Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) ... -  《-》

Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome.

The definition of eosinophilic gastritis (EG) is currently limited to histologic EG based on the tissue eosinophil count. We aimed to provide additional fundamental information about the molecular, histopathologic, and clinical characteristics of EG. Genome-wide transcript profiles and histologic features of gastric biopsy specimens, as well as blood eosinophil counts, were analyzed in patients with EG and control subjects (n = 15 each). The peak gastric antrum eosinophil count was 283 ± 164 eosinophils/×400 high-power field in patients with EG and 11 ± 9 eosinophils/×400 high-power field in control subjects (P = 6.1 × 10(-7)). Patients with EG (87%) had coexisting eosinophilic inflammation in multiple gastrointestinal segments; the esophagus represented the most common secondary site. Increased peripheral blood eosinophil counts (patients with EG: 1.09 ± 0.88 × 10(3)/μL vs control subjects: 0.09 ± 0.08 10(3)/μL, P = .0027) positively correlated with peak gastric eosinophil counts (Pearson r(2) = .8102, P < .0001). MIB-1(+) (proliferating), CD117(+) (mast cells), and FOXP3(+) (regulatory T cells, activated T cells, or both) cell counts were increased in patients with EG. Transcript profiling revealed changes in 8% of the genome in gastric tissue from patients with EG. Only 7% of this EG transcriptome overlapped with the eosinophilic esophagitis transcriptome. Significantly increased IL4, IL5, IL13, IL17, CCL26, and mast cell-specific transcripts and decreased IL33 transcripts were observed. EG is a systemic disorder involving profound blood and gastrointestinal tract eosinophilia, TH2 immunity, and a conserved gastric transcriptome markedly distinct from the eosinophilic esophagitis transcriptome. The data herein define germane cellular and molecular pathways of EG and provide a basis for improving diagnosis and treatment.

Caldwell JM ，Collins MH ，Stucke EM ，Putnam PE ，Franciosi JP ，Kushner JP ，Abonia JP ，Rothenberg ME ... -  《-》

Association Between Endoscopic and Histologic Findings in a Multicenter Retrospective Cohort of Patients with Non-esophageal Eosinophilic Gastrointestinal Disorders.

Pesek RD ，Reed CC ，Collins MH ，Muir AB ，Fulkerson PC ，Menard-Katcher C ，Falk GW ，Kuhl J ，Magier AZ ，Ahmed FN ，Demarshall M ，Gupta A ，Gross J ，Ashorobi T ，Carpenter CL ，Krischer JP ，Gonsalves N ，Hirano I ，Spergel JM ，Gupta SK ，Furuta GT ，Rothenberg ME ，Dellon ES ，Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) ... -  《-》

Prospective Endoscopic Activity Assessment for Eosinophilic Gastritis in a Multisite Cohort.

Eosinophilic gastritis (EG) is a chronic inflammatory disease of the stomach characterized by eosinophil-predominant gastric mucosal inflammation and gastrointestinal symptoms. The aim of this study was to prospectively evaluate endoscopic features in a large series of children and adults with EG to better understand the endoscopic manifestations and develop a standardized instrument for investigations. Data were prospectively collected as part of the Consortium for Eosinophilic Gastrointestinal Disease Researchers, a national collaborative network. Endoscopic features were prospectively recorded using a system specifically developed for EG, the EG Endoscopic Reference System (EG-REFS). Correlations were made between EG-REFS and clinical and histologic features. Of 98 patients with EG, 65 underwent assessments using EG-REFS. The most common findings were erythema (72%), raised lesions (49%), erosions (46%), and granularity (35%); only 8% of patients with active histology (≥30 eosinophils/high-power field) exhibited no endoscopic findings. A strong correlation between EG-REFS scores and physician global assessment of endoscopy severity was demonstrated (Spearman r = 0.84, P < 0.0001). The overall score and specific components of EG-REFS were more common in the antrum than in the fundus or body. EG-REFS severity was significantly correlated with active histology, defined by a threshold of ≥30 eosinophils/high-power field (P = 0.0002). Prospective application of EG-REFS identified gastric features with a strong correlation with physician global assessment of endoscopic activity in EG. Endoscopic features demonstrated greater severity in patients with active histology and a predilection for the gastric antrum. Further development of EG-REFS should improve its utility in clinical studies.

Hirano I ，Collins MH ，King E ，Sun Q ，Chehade M ，Abonia JP ，Bonis PA ，Capocelli KE ，Dellon ES ，Falk GW ，Gonsalves N ，Gupta SK ，Leung J ，Katzka D ，Menard-Katcher P ，Khoury P ，Klion A ，Mukkada VA ，Peterson K ，Shoda T ，Rudman-Spergel AK ，Spergel JA ，Yang GY ，Rothenberg ME ，Aceves SS ，Furuta GT ，CEGIR investigators ... -  《-》

Gene Expression Patterns in Distinct Endoscopic Findings for Eosinophilic Gastritis in Children.

Eosinophilic gastritis (EG) is clinicopathologically characterized by both marked gastric eosinophilia and clinical symptoms. The endoscopic findings in EG vary among patients, leading to clinical confusion. However, little is known about the relationship between precise endoscopic findings and the pathophysiological process responsible for EG. We aimed to elucidate whether the gross endoscopic findings of EG can be classified into distinct gene expression profiles. We enrolled pediatric patients who underwent gastrointestinal endoscopy for clinical symptoms suggestive of eosinophilic gastrointestinal disorder between 2011 and 2016. EG was diagnosed when gastric eosinophilia was greater than or equal to 30 eosinophils/hpf. The gene expression profiles of gastric biopsies were assessed using microarray technology. Patients with EG and control subjects (n = 8, each) were examined. On the microarray, 1,999 genes were differentially expressed between EG and the controls (≥2-fold difference, adjusted P value < .05), including significant upregulation of eotaxin-3 (C-C chemokine ligand 26). The endoscopic findings of patients with EG fell roughly into 2 types, namely, ulcerative and nodular lesions. Despite identifying distinct patterns of gene expression, most differentially regulated genes overlapped between the 2 endoscopic finding types. Several gene ontology terms were enriched in the substantially overlapped genes, but not in each of the distinct genes. Our results strongly indicate that ulcerative and nodular lesions are a single disease, EG, or a variation thereof, in spite of morphological differences. Our findings may contribute to a better understanding of the pathogenesis of EG, as well as to more accurate diagnosis of this disease.

Sato M ，Shoda T ，Shimizu H ，Orihara K ，Futamura K ，Matsuda A ，Yamada Y ，Irie R ，Yoshioka T ，Shimizu T ，Ohya Y ，Nomura I ，Matsumoto K ，Arai K ... -  《-》