Respiratory Syncytial Virus Genotypes, Host Immune Profiles, and Disease Severity in Young Children Hospitalized With Bronchiolitis.

Background: Data on how respiratory syncytial virus (RSV) genotypes influence disease severity and host immune responses is limited. Here, we characterized the genetic variability of RSV during 5 seasons, and evaluated the role of RSV subtypes, genotypes, and viral loads in disease severity and host transcriptional profiles. Methods: A prospective, observational study was carried out, including a convenience sample of healthy infants hospitalized with RSV bronchiolitis. Nasopharyngeal samples for viral load quantitation, typing, and genotyping, and blood samples for transcriptome analyses were obtained within 24 hours of hospitalization. Multivariate models were constructed to identify virologic and clinical variables predictive of clinical outcomes. Results: We enrolled 253 infants (median age 2.1 [25%-75% interquartile range] months). RSV A infections predominated over RSV B and showed greater genotype variability. RSV A/GA2, A/GA5, and RSV B/BA were the most common genotypes identified. Compared to GA2 or BA, infants with GA5 infections had higher viral loads. GA5 infections were associated with longer hospital stay, and with less activation of interferon and increased overexpression of neutrophil genes. Conclusions: 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.

Sex Differences in Blood Transcriptional Profiles and Clinical Phenotypes in Pediatric Patients with Eosinophilic Esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is an increasingly recognized, chronic inflammatory disease. Recent reports suggest clinical differences between males and females. OBJECTIVE: To define the relevant molecular pathways that could be related to clinical phenotypes in children with EoE. METHODS: We performed blood RNA expression analysis in children with newly diagnosed EoE and matched, healthy controls, and applied bioinformatics tools to define EoE host immune biosignatures. Questionnaires and medical records were used to characterize symptoms, esophagogastroduodenoscopy results, and treatment response. RESULTS: Forty-one subjects (aged 2-17 years) were enrolled; the cohort consisted of 27 males and 14 females. Patients were randomly divided into a discovery cohort (21 EoE patients and 12 controls) that identified 544 significant differentially expressed transcripts (P ≤ .01; 1.25-fold change). Those 544 transcripts correctly classified most EoE patients in the validation cohort (n = 20) from healthy controls. Global transcriptional perturbation relative to healthy controls, Molecular Distance to Health scores were greater in EoE patients than controls (P = .003). When we analyzed subjects based on age and sex, males 13 years of age and older were more likely to have food impactions (P = .033) and to have higher endoscopic severity scores (P = .036). Separate group comparisons according to sex identified 294 differentially expressed transcripts in males and 643 transcripts in female EoE patients. Of those, 37 genes were shared and similarly expressed irrespective of sex. CONCLUSIONS: Whole blood transcriptional analysis represents a promising noninvasive tool to assess activity of the immune/inflammatory response in children with EoE. Male and female EoE patients showed robust differences in gene expression suggesting distinct pathogenic endotypes.