Anti-IgE treatment of eosinophil-associated gastrointestinal disorders.
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 FcepsilonRI 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 FcepsilonRI 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).


CONCLUSIONS
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.


CONCLUSIONS
Anti-IgE might be a potential therapy for EGIDs.
Foroughi
Shabnam
S
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Foster
Barbara
B
Kim
Nayoung
N
Bernardino
Leigh B
LB
Scott
Linda M
LM
Hamilton
Robert G
RG
Metcalfe
Dean D
DD
Mannon
Peter J
PJ
Prussin
Calman
C
D000328:Adult; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001491:Basophils / Q000187:drug effects; D004802:Eosinophilia / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D005759:Gastroenteritis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008875:Middle Aged; D000069444:Omalizumab; D012882:Skin Tests
D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C026408:anti-IgE antibodies; D000069444:Omalizumab; D007073:Immunoglobulin E