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Elevated levels of soluble humanleukocyte antigen-G in the airways are a marker for a low-inflammatory endotype of asthma  Steven R. White, MD, Jessie.

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Presentation on theme: "Elevated levels of soluble humanleukocyte antigen-G in the airways are a marker for a low-inflammatory endotype of asthma  Steven R. White, MD, Jessie."— Presentation transcript:

1 Elevated levels of soluble humanleukocyte antigen-G in the airways are a marker for a low-inflammatory endotype of asthma  Steven R. White, MD, Jessie Nicodemus-Johnson, PhD, Bharathi Laxman, PhD, Darcy R. Denner, PhD, Edward T. Naureckas, MD, D. Kyle Hogarth, MD, Randi Stern, MS, Alexa Minc, BA, Julian Solway, MD, Anne Sperling, PhD, Carole Ober, PhD  Journal of Allergy and Clinical Immunology  Volume 140, Issue 3, Pages (September 2017) DOI: /j.jaci Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 sHLA-G concentrations in BAL fluid. A, Subjects grouped by diagnosis. B, Subjects with asthma stratified by Feno, proportion of BAL eosinophils, serum IgE concentration, and absolute number of blood eosinophils. C, Hierarchical clustering and heatmap in 28 control subjects and 56 subjects with asthma based on expression of the IL-13–driven genes CLCA1, POSTN, and SERPINB2 obtained by RNA-seq from endobronchial brushings. These confirm the assignment of subjects to TH2-low and TH2-high groups by threshold analysis. D, Concentration of sHLA-G in BAL fluid in 28 control subjects and 56 subjects with asthma grouped by TH2 gene score generated from RNA-seq analysis of endobronchial brushes. P values generated by Mann-Whitney rank-sum test after multiple testing correction. Number of subjects with asthma in each group is shown in parentheses. CLCA1, Chloride-channel accessory protein 1; POSTN, periostin. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Ingenuity Pathway Analysis networks of HLA-G–correlated genes from WGCNA. A, Module A. This module was positively associated with FEV1, has TNF as a central hub, and contains immunomodulatory molecules such as CCL20 and the HLA-G receptors LILRB1 and LILRB2 (marked). TNF gene expression was positively correlated with TNF protein abundance and with sHLA-G in BAL fluid. B, Module B. This module was negatively correlated with Feno and has ERK1/2 as a central hub. For each network, positive (solid lines) and negative correlations (dashed lines) are shown. Symbols with a red underline have a negative correlation, and symbols with a blue underline have a positive correlation, with gene expression and increased sHLA-G. Shaded molecules are expressed in airway epithelial cells. Symbol shapes are based on IPA pathway assignment. Symbols marked with an asterisk are influenced by IL-13 treatment in airway epithelial cells. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions


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