Histo-blood group secretor status does not influence mucus plugging or asthma exacerbation outcomes

Abstract 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.