Histo-blood group secretor status does not influence mucus plugging or asthma exacerbation outcomes
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.
Authors
- Loren C. Denlinger (ORCID: https://orcid.org/0009-0008-1299-1186)
- Nizar N. Jarjour (ORCID: https://orcid.org/0000-0003-0170-8927)
- Max A. Seibold (ORCID: https://orcid.org/0000-0002-8685-4263)
- Wendy C. Moore (ORCID: https://orcid.org/0000-0001-6869-3059)
- SUZY A. A. COMHAIR (ORCID: https://orcid.org/0000-0003-1918-9002)
- John V. Fahy (ORCID: https://orcid.org/0000-0001-5427-9308)
- Mark L. Schiebler (ORCID: https://orcid.org/0000-0002-9120-5428)
- SERPIL CEM ERZURUM (ORCID: https://orcid.org/0000-0001-5202-9065)
- Mario Castro (ORCID: https://orcid.org/0000-0001-6328-8994)
- Erin D. Gordon (ORCID: https://orcid.org/0000-0001-7723-2297)
- Mats W. Johansson (ORCID: https://orcid.org/0000-0001-5699-978X)
- Annabelle R. Charbit (ORCID: https://orcid.org/0000-0002-5799-0581)
- Kaharu Sumino (ORCID: https://orcid.org/0000-0002-6214-2966)
- Monica Tang
- Elliot Israel (ORCID: https://orcid.org/0000-0002-2470-856X)
- Bruce David Levy (ORCID: https://orcid.org/0000-0001-9515-5731)
- Kritika Khanna (ORCID: https://orcid.org/0000-0003-0463-8442)
- Deborah A. Meyers (ORCID: https://orcid.org/0000-0001-5399-8423)
- Sally E. Wenzel (ORCID: https://orcid.org/0000-0002-4242-0164)
- Prescott G. Woodruff (ORCID: https://orcid.org/0000-0003-3176-0603)
- David T. Mauger (ORCID: https://orcid.org/0000-0002-4663-5285)
- Eugene R. Bleecker
Institutions
- Brigham and Women's Hospital (US)
- Pennsylvania State University (US)
- University of Wisconsin–Madison (US)
- University of Pittsburgh (US)
- University of California, San Francisco (US)
- Washington University in St. Louis (US)
- University of California System (US)
- National Jewish Health (US)
- Cleveland Clinic Lerner College of Medicine (US)
- Mayo Clinic in Arizona (US)
- University of Kansas Medical Center (US)
- Wisconsin Division of Public Health (US)
- Wake Forest University (US)
- University of San Francisco (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- American Journal of Respiratory Cell and Molecular Biology
- Published
- 2026-10-15
- DOI
- https://doi.org/10.1093/ajrcmb/aanag158
- Primary Topic
- Asthma and respiratory diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00