Association of Clinical Reactivity with Sensitization to Allergen Components in Multifood- Allergic Children Sandra Andorf, PhD, Magnus P. Borres, MD,

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Association of Clinical Reactivity with Sensitization to Allergen Components in Multifood- Allergic Children Sandra Andorf, PhD, Magnus P. Borres, MD, PhD, Whitney Block, MSN, NP, Dana Tupa, MS, Jennifer B. Bollyky, MD, Vanitha Sampath, PhD, Arnon Elizur, MD, Jonas Lidholm, PhD, Joseph E. Jones, MS, Stephen J. Galli, MD, Rebecca S. Chinthrajah, MD, Kari C. Nadeau, MD, PhD The Journal of Allergy and Clinical Immunology: In Practice Volume 5, Issue 5, Pages 1325-1334.e4 (September 2017) DOI: 10.1016/j.jaip.2017.01.016 Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure 1 Food allergen and DBPCFC outcome combinations. A, Overview of DBPCFC outcomes in the study population. B, Number of participants who had positive DBPCFCs against different foods. DBPCFC, Double-blind, placebo-controlled food challenge. The Journal of Allergy and Clinical Immunology: In Practice 2017 5, 1325-1334.e4DOI: (10.1016/j.jaip.2017.01.016) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure 2 Concurrent occurrences of food allergies. A, Number of participants who were allergic against a specific food (diagonal) and any pairwise combination of 2 food allergens (intersection of column and row foods). B, Pie charts and numbers showing the Jaccard similarity coefficient. This similarity measure represents the overlap of participants who were allergic against the 2 food allergens adjusted for the number of participants being allergic against each of the food allergens separately. A coefficient of 1 means perfect overlap of participants, and 0 means no participant is allergic against the 2 food allergens. Soy and wheat were excluded because only 2 participants were allergic against each of them. FDR, False discovery rate. The Journal of Allergy and Clinical Immunology: In Practice 2017 5, 1325-1334.e4DOI: (10.1016/j.jaip.2017.01.016) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure 3 Whole food allergen and component IgE levels stratified by DBPCFC outcomes. A, Milk and its components; B, egg and its components; C, peanut and its components; D, hazelnut and its components; E, pistachio, cashew, and its component; F, pecan, walnut, and its components; G, almond, sesame, soy, wheat. Soy and wheat components were not plotted because only 2 values were obtained. (Q value is the FDR adjusted P value). DBPCFC, Double-blind, placebo-controlled food challenge; FDR, false discovery rate. The Journal of Allergy and Clinical Immunology: In Practice 2017 5, 1325-1334.e4DOI: (10.1016/j.jaip.2017.01.016) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure 4 Hierarchical clustering of the component IgE indicates a clustering of components by protein family or origin. Significant clusters (au P < .05) are shown by red rectangles. After FDR adjusting the P value, all rectangles are also significant at Q < .05 (numbers not in plot). Soy and wheat components were excluded in this analysis because of too few positive observations. au, Approximately unbiased; FDR, false discovery rate; PR-10, pathogenesis-related class-10. The Journal of Allergy and Clinical Immunology: In Practice 2017 5, 1325-1334.e4DOI: (10.1016/j.jaip.2017.01.016) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure 5 After adjusting the component IgE levels for age and sex, Ana o 3, Cor a 14, and Jug r 1 levels were significantly different between participants showing a GI reaction during any DBPCFC and those who did not. Q value (FDR adjusted P value) < .05 for all 3 components. DBPCFC, Double-blind, placebo-controlled food challenge; FDR, false discovery rate; GI, gastrointestinal. The Journal of Allergy and Clinical Immunology: In Practice 2017 5, 1325-1334.e4DOI: (10.1016/j.jaip.2017.01.016) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure E1 DBPCFC outcomes for each allergen or allergen pairs. For each single allergen (squares on the diagonal with only blue percentages) or pair of allergens, the number of participants having a DBPCFC performed against the single allergen or both allergens (tested separately) is shown in black (n). The percentages show the portion of these participants who had a positive or negative DBPCFC against the single allergen (on the diagonal) or both allergens (blue % numbers) as well as how many have discordant DBPCFC outcomes for the pair of allergens (pink % numbers). DBPCFC, Double-blind, placebo-controlled food challenge. The Journal of Allergy and Clinical Immunology: In Practice 2017 5, 1325-1334.e4DOI: (10.1016/j.jaip.2017.01.016) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure E2 Whole food allergen and component IgG4 stratified by DBPCFC outcomes. A, Milk and its components; B, egg and its components; C, peanut and its components; D, hazelnut and its components; E, cashew and its component; F, walnut and its components. Turkey boxplots: shown are the medians; the “hinges” represent the 1st and 3rd quartile. The whiskers are the smaller and largest values after outliers are excepted. Outliers are defined as values greater than the 75th percentile plus 1.5 times the interquartile range (IQR), or less than 25th percentile minus 1.5 times the IQR. DBPCFC, Double-blind, placebo-controlled food challenge. The Journal of Allergy and Clinical Immunology: In Practice 2017 5, 1325-1334.e4DOI: (10.1016/j.jaip.2017.01.016) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure E3 Spearman's rank correlation between component IgE and whole allergen extract IgE values. Significant correlations (Q < .05), which show an absolute Spearman's rank correlation of greater than 0.5, are marked with a colored background. Red rectangles mark the components and their respective source food allergens. The Journal of Allergy and Clinical Immunology: In Practice 2017 5, 1325-1334.e4DOI: (10.1016/j.jaip.2017.01.016) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions