Define myeloid-derived suppressor cells and immune profiles in children with respiratory infections
Katherine Bline, MD
BACKGROUND: Children with critical illness due to viral several lower respiratory tract infections (SLRTI), particularly influenza or respiratory syncytial virus, often have evidence of a diminished immune response, which is associated with an increased risk of death. Myeloid-derived suppressor cells (MDSCs) are a population of immune cells known to expand under conditions of critical illness that potently suppress the adaptive immune system, specifically the ability of T cells to proliferate and produce cytokines. GAP: Our understanding of why some previously healthy children become critically ill when infected with a respiratory virus while others have only mild symptoms is limited. One area where the knowledge gap is significant relates to the factors that determine outcomes in children with sLRTI. HYPOTHESIS: We hypothesize that MDSCs are increased in frequency in children with viral sLRTI and contribute to immune suppression and poor outcomes. METHODS: This is a single-center prospective, observational study that will be conducted in a 54-bed pediatric intensive care unit and involve sequential blood sampling of subjects with the primary measured outcome being MDSC frequencies and subtypes. The study population includes children less than 18 years with confirmed RSV or influenza infection that are not known to have immunosuppression or a chronic condition, although children with mild asthma will be included. RESULTS: Pending. IMPACT: The findings of this proposal have the potential to provide a fresh approach to identify novel therapeutic targets for children with sLRTI. Targeting MDSCs unlocks immunotherapies as a new therapeutic paradigm for children with sLRTI.