INTRODUCTION
Allergic asthma is linked to impaired bronchial epithelial secretion of interferons (IFNs) which may be causally linked with the increased risk of viral exacerbations. We have previously shown that allergen immunotherapy (AIT) effectively reduces asthma exacerbations and prevents respiratory infections requiring antibiotics; however, whether AIT alters antiviral immunity is still unknown.
AIMS AND OBJECTIVES
To investigate the effect of house dust mite-sublingual allergen immunotherapy (HDM-SLIT) on the bronchial epithelial antiviral and inflammatory responses in patients with allergic asthma.
METHODS
In this double blind randomized controlled trial (VITAL), adult patients with HDM allergic asthma received HDM-SLIT 12-SQ or placebo for 24-weeks. Bronchoscopy was performed at baseline and at week-24 which included sampling for human bronchial epithelial cells (HBECs). HBECs were cultured at baseline and at week-24 and stimulated with the viral mimic poly(I:C). mRNA expression was quantified by RT-qPCR and protein levels were measured by multiplex ELISA.
RESULTS
Thirty-nine patients were randomized to HDM-SLIT (n=20) or placebo (n=19). HDM-SLIT resulted in increased poly(I:C)-induced expression of IFN-β, both at gene (p=.009) and protein (p=0.02) level. IFN-λ gene expression was also increased (p=0.03), whereas IL-33 tended to be decreased (p=0.09). On the other hand, pro-inflammatory cytokines IL-6 (p=.009) and TNF-α (p=0.08) increased compared with baseline in HDM-SLIT group. There was no significant change in TSLP, IL-4, IL-13, and IL-10.
CONCLUSION
HDM-SLIT improves bronchial epithelial antiviral resistance to viral infection. These results potentially explain the efficacy of HDM-SLIT reducing exacerbations in allergic asthma. Clinical trial registration available at www.
CLINICALTRIALS
gov, ID: NCT04100902.