Perinatal Granulopoiesis and Risk of Pediatric Asthma

Abstract

Many 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. We hypothesized that transcriptional changes associated with multiple epidemiologic risk factors would be mediators of pediatric asthma risk. Using publicly available transcriptomic data from cord blood mononuclear cells, transcription of genes involved in myeloid differentiation were inversely associated with pediatric asthma risk stratification based on multiple perinatal risk factors. This gene signature was validated in an independent prospective cohort and was specifically associated with genes localizing to neutrophil specific granules. Changes in these genes correlated with changes in protein abundance in serum. Umbilical cord blood serum concentration of PGLYRP-1, a specific granule protein, was inversely associated with mid-childhood current asthma and early-teen FEV1/FVCx100. Thus, neutrophil specific granule abundance at birth may predict individual risk for pediatric asthma and pulmonary function in adolescence.

Identification of Type 2-pediatric Asthma Based on Single-cell Transcriptomic Analysis

“…Asthma is a heterogeneous disease, and transcriptome sequencing is often used to study the pathogenesis of asthma and the e cacy of drug intervention in asthma [15][16][17]. Owing to the heterogeneity of asthma, traditional transcriptome sequencing methods based on blood or tissue samples obtain macroscopic results of the cell population, showing the average expression level of the same gene in all cells, rather than the differences between individual cells of the same gene and its role in the pathogenesis of the disease.…”