(627) Markers of Immune Dysregulation in Pediatric Patients With Severe Viral Bronchiolitis

Introduction: Bronchiolitis is a leading cause of hospitalization in children. To date, severe disease is not well understood and there are no biomarkers to predict outcomes. In-situ and animal studies suggest that viral infection, despite canonical induction of Th1 immune responses, can also lead to activation of Th2 immunity, suggesting inappropriate immune response may play a role in the disease process. Using an omics approach, this study mapped the immune response in patients with severe bronchiolitis as compared to mild disease. We hypothesize that patients with severe disease will have differences in cellular immunity and cytokine response as compared to those with mild disease.

Methods: Fourteen patients under the age of 3 years with a respiratory virus were recruited from Mount Sinai Hospital. Patients with chronic illness, known immune deficiency, or bacterial infection were excluded. Peripheral blood mononuclear cells were isolated. Cytometry by time-of-flight (CyTOF) was used to enumerate 34 subtypes of immunologic cells. O-link proteomics was used to measure 92 peripheral blood cytokines. Patients receiving positive pressure ventilation were categorized as severe and patients admitted not receiving positive pressure ventilation were categorized as mild.

Results: Patients with severe disease had significantly fewer CD57+ NK cells as compared to age matched controls with mild disease. Subgroup analysis removing patients receiving steroids showed significant decrease in T-regulatory cells among sicker patients. Th1:Th2 ratio was significantly lower in mild and severe disease compared to non-viral controls. Peripheral cytokines were not notably different among the groups.

Conclusions: Decreased levels of CD57+ NK cells in severe disease suggests that patients have either decreased innate cellular immunity to viral illness or that CD57+ cells are sequestered in the lungs. When patients are sub-grouped, the paucity of t-regulatory cells in sicker patients suggests these cells are either not present or sequestered and unable to regulate immune response. More data is needed to determine if Th2 response is dominant in sicker patients. Future studies will focus on longitudinal data looking at cell populations and cytokines both peripherally and in the lung.