Food, drug, insect sting allergy, and anaphylaxis
Suppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors

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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.

Conclusion

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.

Section snippets

Study design

The study was a 6-month, open-label study of 14 subjects and is described in greater detail in a companion article.2 Briefly, subjects were treated with omalizumab according to the package insert for a period of 6 months. Before the start of treatment, several weeks after the start of treatment, and 6 months after the start of treatment, blood was obtained and basophils were tested for IgE-mediated responses and FcεRI and Syk expression. Also before treatment, subjects were tested with a

Results

As previously reported,2 6 of 14 subjects’ basophil responses to peanut allergen stimulation (AUC of the full dose-response curve) decreased, whereas the 8 remaining subjects showed an increase that averaged 2.9-fold (95% CI, 2.29-fold to 3.41-fold). In our previous study of subjects with cat allergy,1 only 2 of 12 of the subjects showed an increase in the basophil response to cat allergen, only 1 of which was significantly greater than a ratio of 1.0 (posttreatment/baseline). The difference in

Discussion

Recent studies exploring the immunologic changes that accompany treatment with omalizumab have provided some interesting insights into the behavior of basophils and their role in the allergic disease under study. By combining our experiences obtained from a cat allergy study1 and the current peanut study,2 it is possible to perceive a developing pattern. One of the most obvious patterns is the relationship of the basophil response to the specific/total IgE ratio. This is a logical link because

References (15)

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Supported by National Institutes of Health grants AI20253 and AI070345 (to D.W.M.).

Disclosure of potential conflict of interest: D. W. MacGlashan and J. Savage have received research support from the National Institutes of Health (NIH). R. Wood has received consultancy fees from the Asthma and Allergy Foundation of America; is employed by Johns Hopkins University; has provided expert testimony for the NIH; and has received royalties for UpToDate. S. Saini has received research support from the National Institute of Allergy and Infectious Diseases and Genentech; has been provided with medicines by Genentech; has received consultancy fees from Genentech, Novartis, Pharmacyclics, and MedImmune; and has received royalties from UpToDate.

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