Anti-IgE treatment of eosinophil-associated gastrointestinal disorders

Foroughi, Shabnam; Foster, Barbara; Kim, NaYoung; Bernardino, Leigh B.; Scott, Linda M.; Hamilton, Robert G.; Metcalfe, Dean D.; Mannon, Peter J.; Prussin, Calman

doi:10.1016/j.jaci.2007.06.015

« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 120, Issue 3 , Pages 594-601, September 2007

Anti-IgE treatment of eosinophil-associated gastrointestinal disorders

Shabnam Foroughi, MD
- Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
Barbara Foster, MS
- Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
NaYoung Kim, MD
- Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
Leigh B. Bernardino, RN
- Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
Linda M. Scott, CRNP
- Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
Robert G. Hamilton, PhD
- Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md
Dean D. Metcalfe, MD
- Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
Peter J. Mannon, MD
- Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
Calman Prussin, MD
- Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
- Reprint requests: Calman Prussin, MD, Building 10, Room 11C205, NIH, Bethesda, MD 20892-1881.

Received 26 January 2007; received in revised form 6 June 2007; accepted 7 June 2007.

Background

Eosinophil-associated gastrointestinal disorders (EGIDs) are commonly associated with atopy and are being recognized with increasing frequency. Current therapy for EGIDs is inadequate.

Objective

We sought to determine the efficacy of anti-IgE therapy in EGIDs and investigate the role of IgE in disease pathogenesis.

Methods

Nine subjects with EGIDs received omalizumab every 2 weeks for 16 weeks while other therapy was held constant. Blood absolute eosinophil counts, tissue eosinophil counts, symptom scores, and free IgE levels were serially measured. Allergen skin testing and flow cytometry for basophil activation and FcɛRI were determined at baseline and at week 16.

Results

Omalizumab was associated with a decrease in absolute eosinophil count at both the week 16 (34%, P = .004) and combined weeks 12 to 16 (42%, P = .012) time points. Tissue eosinophils decreased in the duodenum (59%) and gastric antrum (69%) but did not reach statistical significance (P = .074 and .098, respectively). Esophageal eosinophil counts remained unchanged. Basophil and dendritic cell FcɛRI expression and free IgE levels were all significantly decreased (P < .005). Omalizumab increased the concentration of allergen required to trigger half-maximal basophil activation by 170-fold. Allergen skin test wheal and erythema responses decreased by 78% and 82%, respectively. Symptom scores were decreased at both the midstudy (63%) and end of study (70%) time points (P < .005 for both).

Conclusion

These results demonstrate that IgE-mediated processes contribute to the generation of eosinophilic inflammation in EGIDs and suggest that anti-IgE therapy might be effective in these disorders.