Suppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors.
BACKGROUND
A recent study of subjects with peanut allergy treated with omalizumab generated some results that were concordant with a study of subjects with cat allergy treated with omalizumab. However, there were differences that provided additional insight into the nature of the cellular responses in allergic subjects.


OBJECTIVE
We sought to determine the cause for failure to suppress the allergen-induced basophil response during treatment with omalizumab.


METHODS
Patients with peanut allergy were treated with omalizumab. Clinical, serologic, and cellular indices relevant to the response of the subjects and their peripheral blood basophil values (specific/total IgE ratio, cell-surface FcεRI expression, and histamine release responses to anti-IgE antibody or peanut allergen) were obtained at 3 times.


RESULTS
After treatment, approximately 60% of the subjects' basophil responses to peanut allergen did not significantly decrease. In 40% of cases, the in vitro basophil response to peanut allergen increased 2- to 7-fold. The increases were associated with 2 primary factors: a high (>10%) specific/total IgE ratio and an increase in the intrinsic response of the basophil to IgE-mediated stimulation. The extent to which the basophil response to peanut allergen increased was inversely correlated with improvement in the patient's ability to tolerate ingestion of peanut.


CONCLUSIONS
The basophil response during treatment with omalizumab is a consequence of 2 competing factors: suppression of allergen-specific IgE on the cell surface versus increased intrinsic sensitivity to IgE-mediated stimulation. In subjects with peanut allergy, the basophil response appears to mitigate against the ability of omalizumab to improve the patient's tolerance of oral allergen.
Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA. dmacglas@jhmi.edu
Donald W
DW
MacGlashan
Jessica H
JH
Savage
Robert A
RA
Wood
Sarbjit S
SS
Saini
D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D002478:Cells, Cultured; D005260:Female; D005500:Follow-Up Studies; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D008297:Male; D000069444:Omalizumab; D021183:Peanut Hypersensitivity / Q000276:immunology / Q000628:therapy*; D017455:Receptors, IgE / Q000378:metabolism*; D016896:Treatment Outcome
D000485:Allergens; D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; C543355:FcepsilonRI alpha-chain, human; D017455:Receptors, IgE; D000069444:Omalizumab; D007073:Immunoglobulin E; D006632:Histamine