Perinatal Granulopoiesis and Risk of Pediatric Asthma

Abstract

AbstractMany perinatal characteristics are associated with risk for pediatric asthma. Identification of biologic processes influenced by these characteristics could facilitate risk stratification or new therapeutic targets. Using publicly available transcriptomic data from CBMCs, transcription of genes involved in myeloid differentiation were inversely associated with pediatric asthma risk stratification based on gestational age at birth, sex, birthweight, and maternal pre-pregnancy BMI. This gene signature was validated in an independent cohort and was specifically associated with genes localizing to neutrophil specific granules. Changes in these genes correlated with changes in protein abundance in serum. CBMC serum levels of PGLYRP-1, a specific granule protein, and sIL6Rα, a membrane protein, were tested for association with pulmonary outcomes. PGLYRP-1 concentration was inversely associated with mid-childhood current asthma and early-teen FEV1/FVC×100. Thus, variation in neutrophil specific granule abundance at birth is associated with individual risk for pediatric asthma and reduced pulmonary function in adolescence.