Elevated regulatory T cells at diagnosis of Coccidioides infection associates with chronicity in pediatric patients Dan Davini, BA, Fouzia Naeem, MD,

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Presentation transcript:

Elevated regulatory T cells at diagnosis of Coccidioides infection associates with chronicity in pediatric patients Dan Davini, BA, Fouzia Naeem, MD, Aron Phong, BS, Mufadhal Al-Kuhlani, PhD, Kristen M. Valentine, BS, James McCarty, MD, David M. Ojcius, PhD, David M. Gravano, PhD, Katrina K. Hoyer, PhD Journal of Allergy and Clinical Immunology Volume 142, Issue 6, Pages 1971-1974.e7 (December 2018) DOI: 10.1016/j.jaci.2018.10.022 Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 TH cells determine disease outcome. PBMCs were assessed for the frequency of (A) adaptive immune populations and (B) CD4+CD45+ TH cells by flow cytometry based on healthy, resolved, or persistent infection status. ANOVA with Bonferroni correction was used at 95% CI. C, Serum was analyzed by flow cytometry for cytokine concentrations shown with the mean and SEM. IL-1α, IL-1β, IL-5, IL-12p70, IL-17A, IL-21, and IL-22 were below the limit of detection, and not shown. D, Individual cytokines are shown. Each dot represents an individual patient, and lines indicate the mean. ANOVA, and then a Fisher least significant difference, was performed. *P < .05, **P < .005, ***P < .0005. Journal of Allergy and Clinical Immunology 2018 142, 1971-1974.e7DOI: (10.1016/j.jaci.2018.10.022) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 CCR5+ Treg cells are a significant predictor of disease outcome. A, Chi-square automatic interaction detection analysis on patients with persistent and resolved disease identifies a relationship between %CD4+ Treg cells and disease outcome. B, Principle-component (PC) analysis on patients with persistent and resolved disease using eosinophil, neutrophil, and %CD4+ Treg cell parameters. C, CITRUS analysis within the CD4+CD45+ population comparing patients with persistent and resolved disease identified several clusters; CD127, CCR5, and CD25 expression is shown for the Treg cell cluster. D, The frequencies of the significant Treg cell cluster between patients with persistent and resolved disease. E, viSNE heatmaps for CD25, CD127, and CCR5 on 2 representative patients. F, Gates were drawn around %CCR5+ Treg cell and %CCR5neg Treg cell (CD4+CD45+CD127lowCD25+) clusters across all samples. Unpaired student t test was performed. Journal of Allergy and Clinical Immunology 2018 142, 1971-1974.e7DOI: (10.1016/j.jaci.2018.10.022) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Immune parameters based on patient hospital status. Complete blood cell count, kidney function, and liver function assays were performed on Coccidioides-infected patients or healthy controls and compared on the basis of (A) hospital status (inpatient or outpatient) or (B) disease outcome (resolved or persistent). C-E, PBMCs from healthy and Coccidioides-infected patients were assessed by flow cytometry. C, Comparisons of monocytes and dendritic-cell frequencies. (D) Frequency comparisons of adaptive immune populations CD4+, CD8+, and B cells, and of (E) CD4+ TH-cell subsets as a percentage of CD4+ T cells. Each dot represents an individual patient, and lines indicate the mean. ANOVA with Bonferroni correction was used with a 95% CI. ALT, Alanine transferase; BUN, blood urea nitrogen; Cr, creatinine; DC, dendritic cell; WBC, white blood cell. *P < .05, **P < .005, ***P < .0005. Journal of Allergy and Clinical Immunology 2018 142, 1971-1974.e7DOI: (10.1016/j.jaci.2018.10.022) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions