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Abstract Background and Aim Our primary aim was to describe the prevalence of immunoglobulin G (IgG) and its subclass IgG4 in immunohistochemistry staining in esophageal biopsy specimens of children with eosinophilic esophagitis (EoE) compared with that of specimens from children with gastroesophageal reflux disease (GERD). Methods Esophageal biopsy specimens from children with EoE or GERD were stained prospectively for IgG and IgG4 antibodies. Subjects with EoE were divided into cohorts with either active EoE or EoE in remission. Active EoE cases were further divided into proton pump inhibitor responsive (PPI‐r) and PPI‐nonresponsive (PPI‐nr) subgroups. Demographic, clinical, and histologic data were compared among groups, including quantified IgG and IgG4 staining, peak eosinophil count, eosinophil‐derived neurotoxin levels, and EoE endoscopic reference score. Results Seventy‐nine children (aged 10.6 ± 5.6 years; 68% male) were enrolled. IgG‐positive cell counts were significantly elevated in those with active EoE (n = 29, 3 [interquartile range, IQR: 2–6]/high‐powered field [HPF]), compared with those having EoE remission (n = 25, 1 [IQR: 0–2]/HPF; P = 0.002) and those with GERD (n = 25, 0 [IQR: 0–0.25]/HPF, P = |