Johansson, Mats W.

Abstract Rationale The activity of fucosyltransferase 2 (FUT2) determines if mucin glycan structures in epithelial mucus include histo-blood group antigens (HBGAs). People with active FUT2 express HBGAs in epithelial mucus secretions and are terms “secretors”, while non-secretors lack HBGAs in their secretions because they have a FUT2 genotype that inactivates the glycosyl transferase. Prior research suggests that secretors who are blood type O (type O secretors) are susceptible to asthma exacerbations1 and that FUT2 knockout mice (functional non-secretors) are protected from mucus plugging in allergen challenge models2,3. We set out here to determine if secretor status influences mucus plug prevalence in asthma and to confirm if type O secretors are susceptible to asthma exacerbations. Methods We determined secretor status in asthma participants from the Severe Asthma Research Program-3 (SARP-3) cohort (N = 507) in two ways, a specific fucose lectin binding assay in sputum and FUT2 genotyping. Blood group type was determined using ABO genotyping. We analyzed mucus plug segment scores, asthma exacerbations rates and other clinical and biological features in patients stratified by secretor status and blood type (non-secretors, type O secretors, and non-type O secretors). Results Secretor status determined by lectin binding in sputum was strongly concordant with genotypic analysis. Within the SARP-3 cohort, 26.2% were non-secretors, 32.3% type were O secretors, and 41.4% were non-type O secretors. Mucus plug segment scores, annualized asthma exacerbation rates, and other measures of asthma severity were similar in non-secretors, type O secretors, and non-type O secretors (Table). Although type O secretors had increased values for fractional exhaled nitric oxide (FeNO) and higher expression of type 2 gene network genes in their sputum cells, measures of sputum eosinophil inflammation were not higher in this subgroup (Table). Conclusion Secretor status does not influence the prevalence of mucus plugging in asthma patients, and we did not confirm a prior report that type O secretors have an increased risk of asthma exacerbation. Although type O secretors have modestly increased FeNO levels and increased expression of type 2 immune genes in their sputum, it is not clear if this is a biologically important signal. 1. Innes et al. AJRCCM; 2011. 2. Saku et al. JACI; 2019. 3. Hara et al. AJRCMB; 2025 This abstract is funded by: The study was supported by the National Institutes of Health grants R01 HL080414 (JVF), P01 HL107202 (JVF), R01 HL164787 (JVF), U10 HL109172 (EI), U10 HL109152 (SEW), U10 HL109257 (MC), U10 HL109250 (SCE), U10 HL109146 (JVF), U10 HL109164 (ERB), U01 HL146002 (BDL), U10 HL109086 (DTM) and Sandler Asthma Basic Research Center at UCSF (JVF). The following companies provided financial support for study activities at the Coordinating and Clinical Centers beyond the third year of patient follow-up: AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Sanofi–Genzyme Regeneron, and Teva. These companies had no role in study design or data analysis, and the only restriction on the funds was that they be used to support the SARP initiative.