Original ResearchFull Report: Clinical—Alimentary TractEosinophilic Esophagitis in Adults Is Associated With IgG4 and Not Mediated by IgE
Section snippets
Materials and Methods
All human studies were approved by the University of Utah Institutional Review Board (IRB) by written participant consent. The omalizumab trial was registered at ClinicalTrials.gov as NCT 00123630, and approved by the University of Utah IRB (protocol 13623). Tissue and sera for IgG4 studies also were IRB approved (protocols 47802, 14543, and 67489). For all studies, eosinophilic esophagitis subjects met standard criteria (≥15 eosinophils/high-power field in esophageal biopsy specimen, not
Omalizumab Trial
In the omalizumab trial, treated subjects had no significant reduction in esophageal eosinophil content and no decrease in symptoms relative to placebo controls (Table 1 and Supplementary Figure 1). Immunostaining confirmed mast cell IgE depletion after treatment (Supplementary Figure 2), without significant changes in the controls. Serum IgE was increased significantly after treatment in omalizumab subjects (P < .001) (Supplementary Table 3) but not the placebo controls, also confirming
Discussion
Omalizumab failed to reduce tissue eosinophils and symptoms. Eosinophilic esophagitis subjects had a 45-fold increase in esophageal tissue IgG4. Extracellular IgG4 staining was granular, resembling immune complexes. The eosinophilic esophagitis resection had a striking IgG4 plasma cell infiltrate. Abundant IgG4 antibodies to the common trigger foods were present in most eosinophilic esophagitis subjects. None of our subjects had a parasitic infection. Only 1 of the resection cases had a tumor,
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This article has an accompanying continuing medical education activity on page e14. Learning Objective: Upon completion of these questions, successful learners will be able to explain the poor performance of IgE-related allergy testing and therapy in adult eosinophilic esophagitis patients and the frequent presence of abundant IgG4.
Conflicts of interest The authors disclose no conflicts.
Funding Supported by a Castell grant (K.A.P.). Novartis funded, but did not interpret or primarily design, the omalizumab trial.
Author names in bold designate shared co-first authors.