Suppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors Donald W. MacGlashan, MD, PhD,

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Presentation transcript:

Suppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors Donald W. MacGlashan, MD, PhD, Jessica H. Savage, MD, Robert A. Wood, MD, Sarbjit S. Saini, MD Journal of Allergy and Clinical Immunology Volume 130, Issue 5, Pages 1130-1135.e5 (November 2012) DOI: 10.1016/j.jaci.2012.05.038 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Summary of factors needed to calculate cell-surface allergen-specific IgE density after treatment with omalizumab: comparison of 2 studies, cat and peanut (the current study). A-C, Mean ± SD. D, Calculated allergen-specific IgE density, which is a product of Fig 1, A-C, and a fourth factor that is similar for the 2 studies (see this article’s Online Repository). Journal of Allergy and Clinical Immunology 2012 130, 1130-1135.e5DOI: (10.1016/j.jaci.2012.05.038) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Distribution of responses obtained from the peanut I study. A, Distribution of the in vitro basophil response to anti-IgE antibody (Ab; AUC); fold change between the pretreatment response (baseline) and the midpoint response. B, Distribution in the in vitro basophil response to peanut allergen (AUC). C, Relationship between the distributions shown in Fig 2, A and B. Journal of Allergy and Clinical Immunology 2012 130, 1130-1135.e5DOI: (10.1016/j.jaci.2012.05.038) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Changes in Syk expression during treatment and relationship of starting to final anti-IgE response. A, The far left column shows the average fold change in the basophil response to anti-IgE antibody, and the 2 right columns show the average fold change in the anti-IgE antibody response or Syk expression for the subset of 8 subjects in whom Syk expression was measured. B, Correlation between the fold upregulation of the anti-IgE antibody response versus change in Syk expression. C, Relationship between the starting anti-IgE antibody response and the fold change in this response at the midpoint visit during treatment with omalizumab. HR, Histamine response. Journal of Allergy and Clinical Immunology 2012 130, 1130-1135.e5DOI: (10.1016/j.jaci.2012.05.038) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 In vitro basophil response to peanut allergen stimulation (AUC of the full peanut dose-response curve) versus 2 parameters of basophil function, percentage of specific/total IgE, and fold increase in the basophil response to stimulation with the panstimulus anti-IgE antibody. Fold changes refer to the responses at the midpoint visit versus the response before (baseline [Bsl]) treatment with omalizumab (ie, Mid/Bsl). Each vertical bar represents the in vitro peanut response for each patient. Journal of Allergy and Clinical Immunology 2012 130, 1130-1135.e5DOI: (10.1016/j.jaci.2012.05.038) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Relationship between the fold change in the in vitro basophil response to peanut allergen (AUC) and the log fold change in tolerated peanut ingestion during OFC (midpoint visit value/baseline visit value). Gray circles represent those subjects who reached the stopping rule for ingestion of peanut at the midpoint OFC, whereas black circles represent those subjects from whom what a ratio could be calculated. The linear regression was fit to the noncapped data points (solid circles). Journal of Allergy and Clinical Immunology 2012 130, 1130-1135.e5DOI: (10.1016/j.jaci.2012.05.038) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Relationship between the decrease in receptor expression on basophils during treatment with omalizumab and the ratio of occupied to total FcεRI. Journal of Allergy and Clinical Immunology 2012 130, 1130-1135.e5DOI: (10.1016/j.jaci.2012.05.038) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 In vitro basophil response to peanut allergen stimulation divided according to both the peanut-specific/total IgE ratio and the relative increase in the response to anti-IgE antibody (midpoint/baseline). The dividing points for the specific/total ratios (S/T) were greater or less than 4% peanut specific. The thresholds for the increase in the anti-IgE response (Fx aIgE) were a less than 1.5-fold and greater than 1.5-fold change. Dose-response curves: solid circles, pretreatment or baseline; open circles, midpoint. Averages ± SEMs are shown. The numbers under the panel designation represent the average number of peanut-specific IgE molecules per basophil in the specific category. This number is calculated from the known specific/total IgE ratio and the remaining IgE measured on the basophils after treatment. Journal of Allergy and Clinical Immunology 2012 130, 1130-1135.e5DOI: (10.1016/j.jaci.2012.05.038) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Dose-response curves to BPO(21)-HSA stimulation in basophils sensitized with 2 densities of BPO (penicillin)–specific IgE. The data for 4 different experiments are plotted as faded symbols, and heuristic Gaussian curves are fit to all the data points for the 2 conditions. The vertical gray lines mark the peaks of the fit curves, and the dashed vertical gray lines mark the point of 50% of the maximal response. The density of BPO-specific IgE is 15,000 ± 5,000 (green line) and 128,000 ± 50,000 (red line) for the 2 conditions. Journal of Allergy and Clinical Immunology 2012 130, 1130-1135.e5DOI: (10.1016/j.jaci.2012.05.038) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions