Donald W. MacGlashan, MD, PhD, Sarbjit S. Saini, MD

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Presentation transcript:

Omalizumab increases the intrinsic sensitivity of human basophils to IgE-mediated stimulation Donald W. MacGlashan, MD, PhD, Sarbjit S. Saini, MD Journal of Allergy and Clinical Immunology Volume 132, Issue 4, Pages 906-911.e4 (October 2013) DOI: 10.1016/j.jaci.2013.04.056 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Sensitivity curves for subjects treated with omalizumab or placebo. A, Placebo-treated subjects (n = 9). Solid circles, Average baseline sensitivity curve; open circles, average sensitivity curve at the midpoint of the study (approximately 6-8 weeks); and solid squares, average sensitivity curve at approximately 12 weeks just before cessation of drug dosing. B, Omalizumab-treated subjects (n = 10). Solid circles, Average baseline sensitivity curve; open circles, average sensitivity curve at the midpoint of the study (approximately 6-8 weeks); and solid squares, average sensitivity curve at approximately 12 weeks. The dotted line provides a visual reference for the change in sensitivity. Journal of Allergy and Clinical Immunology 2013 132, 906-911.e4DOI: (10.1016/j.jaci.2013.04.056) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Relationships in change in sensitivity and starting sensitivity or starting maximum HR. A, Starting sensitivity (ED50) as measured in units of mean fluorescence intensity from flow cytometric measurements. B, Relationship between starting maximum HR and change in sensitivity. Journal of Allergy and Clinical Immunology 2013 132, 906-911.e4DOI: (10.1016/j.jaci.2013.04.056) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Sensitivity measurements using LTC4 secretion as the outcome. LTC4 levels were measured in the same supernatants in which HR was measured. The data are from only subjects treated with omalizumab (n = 7) and for whom data were available at each of the 3 time points (baseline, 6-8 weeks, and 12 weeks). Journal of Allergy and Clinical Immunology 2013 132, 906-911.e4DOI: (10.1016/j.jaci.2013.04.056) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Recovery of baseline sensitivity after cessation of omalizumab treatment (n = 7). Solid squares, Average baseline sensitivity curve for the 7 subjects who completed the recovery period; open circles, average sensitivity curve at 12 weeks; and solid squares, average sensitivity curve 3 months after cessation of omalizumab. Journal of Allergy and Clinical Immunology 2013 132, 906-911.e4DOI: (10.1016/j.jaci.2013.04.056) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Example of data analysis for the determination of changes in basophil sensitivity. A, An example data set from one of the subjects in the study. Data represent the baseline sensitivity curve. B, Normalization of the curve in Fig E1, A, using the maximal HR and ED50 points defined in Fig E1, A. C, Normalized results from all 19 baseline curves in the study are combined into one baseline curve and data fit by using a sigmoid function. The gray vertical bands in the plot represent regions in which results are averaged into a single data point for the purposes of presentation (see text). Journal of Allergy and Clinical Immunology 2013 132, 906-911.e4DOI: (10.1016/j.jaci.2013.04.056) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Individual plots for the treated group (n = 10). A-J, The abscissa is expressed in flow cytometric (net) mean fluorescence intensity units (see text for calibration), and the ordinate is expressed as percentage HR at the baseline visit (black circles), midpoint visit (blue circles), and final visit (green squares). Along the right side of each panel are colored tick marks (same color assignments) that indicate the maximum anti-IgE antibody–induced release for the 3 time points. K and L show the fitting results for all 10 treated or 9 placebo data sets, and the shading represents the error envelope around the central fit curve: black shows the baseline visit, orange is the midpoint visit, and green is the final time point visit. Journal of Allergy and Clinical Immunology 2013 132, 906-911.e4DOI: (10.1016/j.jaci.2013.04.056) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Anti-IgE dose-response curves at baseline and 12 weeks after treatment with omalizumab (n = 3). Solid circles, Baseline; open circles, 12 weeks. The inset shows the same data normalized to visually appreciate the curve shift. The dark gray band in the inset shows the choices of anti-IgE antibody concentration used in previous studies. Journal of Allergy and Clinical Immunology 2013 132, 906-911.e4DOI: (10.1016/j.jaci.2013.04.056) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions