Esophageal epithelial immunoglobulin G is an important marker for the diagnosis and management of pediatric eosinophilic esophagitis

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 = <0.0001). IgG-positive cell counts were significantly higher in the PPI-r (n = 15, 5 [IQR: 2.5-11]/HPF) subgroup, compared with the PPI-nr subgroup (n = 11, 3 [IQR: 1.5-3.5]/HPF; P = 0.041) at baseline endoscopy.

Conclusion: Initial esophageal tissue biopsy specimens from pediatric subjects with active EoE showed a significant increase in IgG-positive staining compared with tissue from subjects in EoE remission or with GERD. There was higher positivity of IgG-stained cells in the PPI-r subgroup compared with the PPI-nr subgroup.

Keywords: eosinophilic esophagitis; eosinophil‐derived neurotoxin; gastroesophageal reflux disease; immunoglobulin G; immunoglobulin G4; immunohistochemistry; proton pump inhibitors.

Figure 1

(a) Box and whisker plots showing immunoglobulin G (IgG)‐positive staining was significantly elevated in active eosinophilic esophagitis (EoE) compared with EoE in remission and gastroesophageal reflux disease (GERD). (b) Box and whisker plots showing that in the active EoE group the IgG‐positive cell counts were significantly higher in the proton pump inhibitor (PPI) responsive subgroup compared with nonresponsive subgroup at baseline endoscopy. HPF, high‐powered field.

Figure 2

Epithelial immunoglobulin G (IgG) and IgG4 staining at 400× magnification showing increased IgG and IgG4 in active eosinophilic esophagitis (EoE) compared with EoE in remission and gastroesophageal reflux disease (GERD). (a1) GERD HE staining showing basal cell hyperplasia and lamina propria papillae elongation into upper epithelium. (a2) IgG staining in GERD. (a3) IgG4 staining in GERD. (b1) Active EoE (HE stain) showing increased eosinophils in squamous mucosa concentrated in the surface epithelium. (b2) IgG staining in active EoE showing positive lymphocytes located between epithelial cells. (b3) IgG4 staining in active EoE showing some background positive lymphocytes. (c1) Remission EoE (HE stain) showing absent eosinophils within the surface epithelium. (c2) IgG staining in remission EoE showing scant positivity in lymphocytes located between epithelial cells. (c3) IgG4 staining in remission EoE.

Figure 3

Immunoglobulin G (IgG) and IgG4 staining (400× magnification) showing increase IgG4 and IgG in proton pump inhibitor responsive (PPI‐r) EoE at baseline endoscopy. (a1) Increased IgG expression in PPI‐r eosinophilic esophagitis (EoE). IgG‐positive lymphocytes are located between epithelial cells in a background of nonspecific staining. (a2) Increased IgG4 expression in PPI‐r EoE. Occasional IgG4‐positive lymphocytes are seen located between epithelial cells in a background of nonspecific epithelial staining.