RSV A infections were more frequent than RSV B, and displayed greater variability. GA5 infections were associated with enhanced disease severity and distinct host immune responses.

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Acute chest syndrome (ACS) is a significant cause of morbidity and mortality in sickle cell disease (SCD), but preventive, diagnostic, and therapeutic options are limited. Further, ACS and acute vasoccclusive pain crises (VOC) have overlapping features, which causes diagnostic dilemmas. We explored changes in gene expression profiles among patients with SCD hospitalized for VOC and ACS episodes to better understand ACS disease pathogenesis. Whole blood RNA-Seq was performed for 20 samples from children with SCD at baseline and during a hospitalization for either an ACS (n = 10) or a VOC episode (n = 10). Respiratory viruses were identified from nasopharyngeal swabs. Functional gene analyses were performed using modular repertoires, IPA, Gene Ontology, and NetworkAnalyst 3.0. The VOC group had a numerically higher percentage of female, older, and hemoglobin SS participants compared to the ACS group. Viruses were detected in 50% of ACS cases and 20% of VOC cases. We identified 3004 transcripts that were differentially expressed during ACS episodes, and 1802 transcripts during VOC episodes. Top canonical pathways during ACS episodes were related to interferon signaling, neuro-inflammation, pattern recognition receptors, and macrophages. Top canonical pathways in patients with VOC included IL-10 signaling, iNOS signaling, IL-6 signaling, and B cell signaling. Several genes related to antimicrobial function were down-regulated during ACS compared to VOC. Gene enrichment nodal interactions demonstrated significantly altered pathways during ACS and VOC. A complex network of changes in innate and adaptive immune gene expression were identified during both ACS and VOC episodes. These results provide unique insights into changes during acute events in children with SCD.

Background Influenza immunization during pregnancy provides protection to the mother and the infant. Studies in adults and children with inactivated influenza vaccine (IIV) have identified changes in immune gene expression that correlated with antibody responses. Objective To define baseline blood transcriptional profiles and changes induced by IIV in pregnant women and to identify correlates with antibody responses. Methods Pregnant women were immunized with IIV during the 2013-14 and 2014-15 seasons. Blood samples were collected on day (d) 0 (pre-vaccination), d1 and d7 post-vaccination for transcriptional profile analyses; and d0, d30, delivery and cord blood to measure antibody titers. Results Transcriptional analysis demonstrated overexpression of interferon-stimulated genes (ISGs) on d1 and of plasma cell genes on d7. Pre-vaccination ISGs expression and ISGs over-expressed on d1 significantly correlated with increased H3N2, B Yamagata and B Victoria antibody titers. Plasma-cell gene expression on d7 correlated with increased B Yamagata and B Victoria antibody titers. Compared with women vaccinated during the previous influenza season, women who were not vaccinated the prior year showed more frequent significant correlations between ISGs and antibody titers Conclusions Influenza vaccination in pregnant women resulted in enhanced expression of ISGs and plasma cell genes that correlated with antibody responses.

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The original version of this Article contained a typographical error in the spelling of the author Asuncion Mejias which was incorrectly given as M. Asuncion Mejias.

BackgroundRSV is the leading cause of hospitalization for bronchiolitis in infants and young children worldwide. Second-hand smoke (SHS) exposure has been associated with increased morbidity in children with respiratory infections. The objectives of this study were to explore the association between SHS measured by hair nicotine and disease severity in infants with RSV infection, and to define its impact on the blood transcriptional immune profiles.MethodsSingle-center, prospective study of previously healthy infants presenting to the Emergency Department with RSV bronchiolitis with and without SHS exposure assessed by hair nicotine levels. Exclusion criteria included: prematurity; chronic medical conditions, and insufficient hair. Clinical outcomes were assessed using a clinical disease severity score (CDSS; ranging from 0 to 15) and care provided (hospitalization and intensive care). Blood samples from patients and healthy controls were obtained at enrollment for gene expression profiling, and differences in profiles stratified by SHS exposure.ResultsA total of 70 infants with RSV were enrolled (median age 2.7 months; 44 (62.8%) males; 44 (62.8%) white). Hair nicotine was detected in 45 (64.2%) infants with RSV while 25 RSV+ infants had undetectable hair nicotine levels. Demographic variables were not significantly different between SHS exposed and nonexposed infants. Median nicotine concentrations in infants with severe (CDSS >10) vs. mild RSV disease (CDSS < 5) were 5.3 and 2.1ng/mg (P = 0.49). In addition, blood transcriptional profiles in RSV infants exposed to SHS vs. nonexposed, were characterized by significantly greater overexpression of genes related to inflammation, apoptosis and cell death, and greater suppression of T and B cell-related genes (Figure 1).ConclusionIn otherwise healthy infants with RSV infection exposure to SHS was associated with greater inflammation and blunted T and B cell responses. Although not statistically significant, hair nicotine levels were higher in patients with more severe RSV bronchiolitis.Disclosures O. Ramilo, Abbvie: Board Member, Consulting fee; Regeneron: Board Member, Consulting fee; Janssen: Board Member and Investigator, Consulting fee and Research grant; NIH: Grant Investigator, Research grant; A. Mejias, Janssen: Investigator and Scientific Advisor, Consulting fee and Research support; Abbvie: Consultant and Scientific Advisor, Speaker honorarium; Novartis: CME lecture, Speaker honorarium; NIH: Investigator, Research grant