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Severe Asthma Research - December 2016

Christina E Ciaccio, MD, MSc

Christina E Ciaccio, MD, MSc
Allergist/Immunologist
Assistant Professor of Pediatrics
University of Chicago Medicine
Comer Children’s Hospital
Chicago, Illinois, United States

Dysregulation of lipidomic progile and antiviral immunity in response to hyaluronan in patients with severe asthma

Hyaluronan is a potential biomarker of severe asthma that correlates with disease severity.  The authors previously showed that low-molecular-weight hyaluronan (LMW HN) activates arachidonic acid production.  This study looks at the effect of LMW HA on the lipidomic profile and global gene expression in asthmatics of PBMCs of patients with varying severity of asthma (13 asthmatics; 6 controls).  Sixty-eight lipid species were detected before or after LMW HA stimulation.  Twenty-two lipids were upregulated after LMW HA stimulation.  Of these, 9 had a more pronounced increased in asthmatics than controls.  In addition, stimulation with LMW HA led to an increase in gene expression of 177 genes in canonical pathways.  Using multiplex assay, 6 canonical pathways were significantly changed in patients with severe asthma versus controls and were primarily from antimicrobial response, including antiviral response, antibacterial response, and lymphocyte movement and homing.  Finally, the authors used the collected data to build a model of LMW HA-dependent signaling impairments which predicted that less upregulated gene expression in the interferon signaling pathways impaired activation of antimicrobial responses in patients with severe asthma.  These data provide evidence for a connection between the extracellular matrix component HA, lipid mediator production and antiviral responses in patients with severe asthma.

Sokolowska M, Chen LY, Liu Y, Martinez-Anton A, Logun C. Dysregulation of lipidomic progile and antiviral immunity in response to hyaluronan in patients with severe asthma. Journal of Allergy and Clinical Immunology 2016; published online ahead of print, November 5. (doi:10.1016/j.jaci.2016.09.031)

Summary