Th167 - The Lung Innate and Adaptive Response in Pediatric Acute Respiratory Distress Syndrome

Salvatore Albani – Singhealth Translational Immunology Institute; Jing Yao Leong – Singhealth Translational Immunology Institute; Yee Hui Mok – K K Women's and Children's Hospital; Sharifah Nur hazirah – Singhealth Translational Immunology Institute; Joo Guan Yeo – Singhealth Translational Immunology Institute; Nicholas Khoo – Singhealth Translational Immunology Institute

Abstract Text: Children are susceptible to viral lung infections due to immune immaturity. Occasionally, viral lung infections progress to acute respiratory distress syndrome (ARDS) with poor clinical outcomes. Here, the pulmonary innate and adaptive immune pathways that contribute to pediatric ARDS pathogenesis is studied with a theragnostic translational goal of identifying prognostic immune signatures associated with greater disease severity and druggable targets. 19 children with pediatric ARDS and 12 children with no lung injury (controls) were studied. Deep tracheal lavage samples were obtained and CD3+ T cells and CD14+ myeloid cells isolated using fluorescence-activated cell sorting (FACS). Transcriptomics analysis using the NanoString nCounter system was performed to characterize lymphocyte and myeloid gene expression. Gene set enrichment analysis was performed on DAVID Bioinformatics Resources 6.8 and upregulated pathways identified.

115 lymphocyte genes were significantly up-regulated. Pathways associated with ongoing inflammation, specifically T cell receptor signaling, immune activation (type I and II interferon, TNF and downstream NFKB pathways) and cell adhesion/migration genes were up-regulated in pediatric ARDS compared to control. Severity of pediatric ARDS was specifically associated with upregulation of T cell cytotoxic (GZMA, GZMB, GNLY), exhaustion/inhibition (CTLA4, PDCD1, LAG3, TIGIT) and apoptosis (ABL1, ATG5, BAX, BCL2) genes. Myeloid genes (169) were predominantly downregulated with decreased antigen presenting function (MHC class II HLA genes), pattern recognition (TLR2, TLR4) and anti-inflammatory potential (CD163, IL10). These results aid in understanding how the over-exuberant inflammatory responses are skewed and may provide theragnostic opportunities associated with disease severity and druggable targets.