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Histo-blood group secretor status does not influence mucus plugging or asthma exacerbation outcomes
Kritika Khanna1, Annabelle R Charbit1, Monica Tang2
1Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA.
Rationale:
Fucosyltransferase2 (FUT2) activity in airway epithelial cells (AECs) determines if histo-blood group antigens (HBGAs) are components of mucin glycans. "Secretors" (with at least one functioning copy of FUT2) have HBGA-decorated mucins, whereas "non-secretors" (homozygous for null mutations in FUT2) do not. Prior research in animal models of asthma and in human asthma suggests that non-secretor status protects against mucus plugging and that type O secretors are prone to exacerbations.
Methods:
Secretor status was determined in 507 participants in the Severe Asthma Research Program-3 (SARP-3) using a fucose lectin binding assay in sputum and FUT2 genotyping. Blood group was determined using ABO genotyping. Mucus plugging was assessed using the computed tomography (CT)-derived mucus plug segment score, and exacerbation frequency was determined prospectively. We also explored the functional effects of secretor status on mucin outcomes in AECs in culture.
Results:
Secretor status determined by lectin binding in sputum was strongly concordant with FUT2 genotype. Among the SARP-3 participants, 26.2% were non-secretors, 32.3% were type O secretors, and 41.4% were non-type O secretors. Mucus plug segment scores were similar in secretor and non-secretor subgroups, and exacerbation rates were similar in type O secretors and other secretor subgroups. Mucin gene expression in AECs from secretors and non-secretor donors was similar, as were measures of mucociliary clearance and mucus gel viscosity and elasticity.
Conclusion:
Secretor status does not influence mucus plugging or exacerbation outcomes in the SARP-3 cohort, and it does not have significant effects on mucin expression or biophysical properties of airway mucus.
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