Higher B-cell activating factor levels at birth are positively associated with maternal dairy farm exposure and negatively related to allergy development

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Presentation transcript:

Higher B-cell activating factor levels at birth are positively associated with maternal dairy farm exposure and negatively related to allergy development Anna-Carin Lundell, PhD, Bill Hesselmar, MD, PhD, Inger Nordström, BSc, Ingegerd Adlerberth, MD, PhD, Agnes E. Wold, MD, PhD, Anna Rudin, MD, PhD Journal of Allergy and Clinical Immunology Volume 136, Issue 4, Pages 1074-1082.e3 (October 2015) DOI: 10.1016/j.jaci.2015.03.022 Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Circulating BAFF levels are maximal at birth. BAFF levels in plasma at birth and at 1, 4, 18, and 36 months of age and in maternal plasma. Maternal plasma was obtained either during pregnancy or after delivery (median values: 19 days before and 30 days after giving birth, respectively). Horizontal bars indicate medians. ****P ≤ .0001, Mann-Whitney U test and ANOVA posttest for linear trend. Journal of Allergy and Clinical Immunology 2015 136, 1074-1082.e3DOI: (10.1016/j.jaci.2015.03.022) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Farmers' children have higher BAFF levels at birth than nonfarmers' children. A, OPLS column loading plots depicting association between BAFF levels at birth (Y-variable) in relation to X-variables, including farming environment, sex, elder sibling, pets at home, delivery mode, birth weight, maternal age at delivery, and maternal history of allergy. R2Y indicates how well the variation of the Y-variable is explained, and Q2 indicates how well the Y-variable can be predicted. B, BAFF levels in plasma at birth among farmers' and nonfarmers' children. Open and solid symbols indicate female and male sex, respectively. C, BAFF levels in cord blood from girls and boys. Open and solid symbols indicate farmers' and nonfarmers' children, respectively. D and E, Correlations between maternal and infant BAFF levels among farming and nonfarming families. Horizontal bars indicate medians. *P ≤ .05 and **P ≤ .01, Mann-Whitney U test (Fig 2, B and C) and Spearman correlation test (Fig 2, D-E). Journal of Allergy and Clinical Immunology 2015 136, 1074-1082.e3DOI: (10.1016/j.jaci.2015.03.022) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Higher BAFF levels at birth are associated with a higher degree of B-cell maturation in the circulation later in childhood. A and C, OPLS column loading plots depicting association between BAFF levels at birth among nonfarmers' children (Fig 3, A) or farmers' children (Y-variable; Fig 3, C) in relation to X-variables, including numbers of CD20+ B cells, proportions of immature/naive CD5+ or memory CD27+ B cells, and total levels of IgM, IgG, IgA, and BAFF measured in blood on repeated occasions from birth up to 36 months of age. The OPLS column plots are based on B-cell variables with VIP values of greater than 0.9. R2Y indicates how well the variation of the Y-variable is explained, and Q2 indicates how well the Y-variable can be predicted. B, Correlation between BAFF levels at birth and proportions of CD5+ B cells at 3 to 5 days of age among nonfarmers' children. D, Correlation between BAFF levels at birth and proportions of CD27+ B cells at 4 months of age among farmers' children. Fig 3, B and D, Spearman correlation test. Journal of Allergy and Clinical Immunology 2015 136, 1074-1082.e3DOI: (10.1016/j.jaci.2015.03.022) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Cord blood BAFF levels and development of allergic disease. BAFF levels at birth in nonallergic children and children given a diagnosis of any allergic disease (ie, food allergy, eczema, asthma, and/or allergic rhinoconjunctivitis) at 18 (A) and 36 (B) months of age, respectively. Open symbols indicate farmers' children. Horizontal bars show medians. *P ≤ .05, Mann-Whitney U test. Journal of Allergy and Clinical Immunology 2015 136, 1074-1082.e3DOI: (10.1016/j.jaci.2015.03.022) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Boys and girls differ with respect to postnatal B-cell maturation. A, OPLS discriminant analysis column loading plot depicting associations between sexes and B-cell variables. The OPLS discriminant analysis column plot is based on variables with VIP values of greater than 1.1. R2Y indicates how well the variation of the Y variable is explained, and Q2 indicates how well the Y variable can be predicted. B, Proportion of CD5+ B cells within CD20+ total B cells in blood from boys and girls at several time points in the first 36 months of life. Horizontal bars indicate median. *P ≤ .05, **P ≤ .01, and ***P ≤ .001, Mann-Whitney U test. Journal of Allergy and Clinical Immunology 2015 136, 1074-1082.e3DOI: (10.1016/j.jaci.2015.03.022) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Gating strategy for lymphocytes and CD20+ B cells, with zebra plots demonstrating the proportion of immature transitional, mature naive, or memory B cells based on CD24 and CD38 expression within the CD5+ or CD5− B-cell subsets in blood from 1 newborn child and 1 8-year-old child. The following mAbs were used: APC-H7–conjugated anti-CD20 (clone L27, BD Biosciences), phycoerythrin-Cy7–conjugated anti-CD24 (clone ML5, BD Biosciences), phycoerythrin-conjugated anti-CD38 (clone HB7, BD Biosciences), APC-conjugated CD5 (clone UCHT2; PharMingen, San Diego, Calif), and FITC-conjugated anti-CD27 (clone L128, BD Biosciences). All samples were run in a FACSCanto II (BD Biosciences) equipped with FACSDiva software and analyzed with FlowJo software. FSC, Forward scatter; SSC, side scatter. Journal of Allergy and Clinical Immunology 2015 136, 1074-1082.e3DOI: (10.1016/j.jaci.2015.03.022) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 A, Numbers of circulating B cells within the lymphocyte gate at birth and at 1, 4, 18, and 36 months of age. B and C, Correlation plots depicting BAFF levels in relation to B-cell counts at birth and 36 months of age, respectively. Fig E2, A, Horizontal bars indicate medians. ****P ≤ .0001, Kruskal-Wallis test, followed by the Dunn multiple-comparison test. Fig E2, B and C, Spearman correlation test. Fig E2, A, All data regarding B-cell numbers have been published previously by Lundell et al.5 Journal of Allergy and Clinical Immunology 2015 136, 1074-1082.e3DOI: (10.1016/j.jaci.2015.03.022) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions