Immune factors in breast milk related to infant milk allergy are independent of maternal atopy Kirsi M. Järvinen, MD, PhD, Mayte Suárez-Fariñas, PhD,

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Immune factors in breast milk related to infant milk allergy are independent of maternal atopy Kirsi M. Järvinen, MD, PhD, Mayte Suárez-Fariñas, PhD, Erkki Savilahti, MD, PhD, Hugh A. Sampson, MD, M. Cecilia Berin, PhD Journal of Allergy and Clinical Immunology Volume 135, Issue 5, Pages 1390-1393.e6 (May 2015) DOI: 10.1016/j.jaci.2014.10.051 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Human milk immune markers that were different between mothers with a CMA infant and those with a non-CMA infant. A, IL-1β. B, IL-6. C, IL-10. D, TSLP (t test, shown after logarithmic transformation). E, Multivariate score combining all 4 cytokines A-D (multivariate U-statistics). On the box plots' horizontal line, median; box, 25th to 75th percentile; whiskers, 5th to 95th percentile; round symbol, geometric mean. Journal of Allergy and Clinical Immunology 2015 135, 1390-1393.e6DOI: (10.1016/j.jaci.2014.10.051) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 A, Hierarchical cluster analysis of human milk immune factors using Spearman correlation and average agglomeration algorithm. Correlation coefficient associated color coding shown; *P < .05, **P < .01, ***P < .001. P values (as %) in blue in the resultant dendrogram indicate the degree of stability of each cluster. Height of ≤0.4 indicates clusters of significant correlation. Clusters C1, C2, and C3, and subclusters (a-d) were identified. B, Multivariate μ score combining all markers in the cluster (multivariate U-statistics). Journal of Allergy and Clinical Immunology 2015 135, 1390-1393.e6DOI: (10.1016/j.jaci.2014.10.051) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Spearman rank correlation of human milk factors, including cytokines, chemokines, growth factors, specific IgA, leukocyte proportion, age of baby (ie, duration of lactation), and age of mother. Shown are the correlation coefficient and color coding corresponding to values between −1.0 and 1.0, indicating negative and positive correlation, respectively. *P < .05, **P < .01, ***P < .001. BLG, Beta-lactoglobulin; CS, casein; ECP, eosinophil cationic protein; eos, eosinophil; gran, granulocyte; lymf, lymphocyte; mf, macrophage/secretory epithelial cell; mono, monocyte; neutr, neutrophil. Journal of Allergy and Clinical Immunology 2015 135, 1390-1393.e6DOI: (10.1016/j.jaci.2014.10.051) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Classification and regression tree with input from human milk levels of cytokines, chemokines, growth factors, specific IgA, and maternal demographics. This model correctly classified CMA outcome in 80% of the samples. Numbers in blue indicate healthy infants, and numbers in red indicate CMA infants. There are 15 misclassified patients: 9 healthy subjects were misclassified as CMA (7+2+0; see the blue numbers arriving to the red nodes), and 6 CMA patients were misclassified as healthy (0+1+5; see red numbers arriving to the blue nodes). Journal of Allergy and Clinical Immunology 2015 135, 1390-1393.e6DOI: (10.1016/j.jaci.2014.10.051) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions