Food, drug, insect sting allergy, and anaphylaxisSuppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors
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
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Response of peripheral blood basophils in subjects with chronic spontaneous urticaria during treatment with omalizumab
2021, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Furthermore, dosing for CSU is not based on circulating IgE titer and weight, and so the levels of free IgE may or may not be less blunted. The observation that the final levels of FcεRI expression are higher (as a fraction of the starting density) than those found in previous studies(in subjects with asthma, 15% to 20% of starting levels;21,22 in subjects with peanut allergy,14 25% of starting levels) and here in subjects with CSU, 45% may suggest that the dosing is not as effective at the level of basophil receptor expression and therefore higher than found in subjects with asthma and peanut allergy (which both used the same dosing tables). With respect to basophil behavior during treatment with omalizumab, the study of CSU provided a unique opportunity to explore this therapeutic in a disease that is sometimes accompanied by the presence of auto-antibodies to the target of the therapeutic or a collateral target, in this case, FcεRI.
Effects of omalizumab on basophils: Potential biomarkers in asthma and chronic spontaneous urticaria
2020, Cellular ImmunologyCitation Excerpt :This IgE status counterbalanced the increased Syk-related basophil sensitivity, resulting in the suppression of the overall basophil response [43,47]. The same research group described similar findings in food (peanut) allergy, suggesting that the response to omalizumab may be the result of two opposite basophil-related factors, namely the cell density of antigen-specific IgE (related to the variable specific/total IgE ratio) and the increased basophil sensitivity to IgE-mediated stimulation [48]. As mentioned above, the latter aspect may better predict the successful therapeutic response, whereas the analysis of the specific/total IgE ratio resulted to be less predictive (probably, several perennial and seasonal allergens can be concomitantly and variably implicated in the same asthmatic patients) [46].
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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.