The H antigen at epithelial surfaces is associated with susceptibility to asthma exacerbation

Abstract

Rationale: Acute asthma exacerbations, precipitated by viral infections, are a significant cause of morbidity, but not all patients with asthma are equally susceptible.

Objectives: To explore susceptibility factors for asthma exacerbations, we considered a role for histoblood group antigens because they are implicated in mechanisms of gastrointestinal viral infection, specifically the O-secretor mucin glycan phenotype. We investigated if this phenotype is associated with susceptibility to asthma exacerbation.

Methods: We performed two consecutive case-control studies in subjects with asthma who were either prone or resistant to asthma exacerbations. Exacerbation-prone cases had frequent use of prednisone for an asthma exacerbation and frequent asthma-related healthcare utilization, whereas exacerbation-resistant control subjects had rarely reported asthma exacerbations. The frequency of different mucin glycan phenotypes, defined by the presence or absence of H (O), A, B, or AB antigens, was compared in cases and control subjects.

Measurements and main results: In an initial study consisting of 49 subjects with asthma (23 cases and 26 control subjects), we found that having the O-secretor phenotype was associated with a 5.8-fold increase in the odds of being a case (95% confidence interval, 1.7-21.0; P = 0.006). In a replication study consisting of 204 subjects with asthma (101 cases and 103 control subjects), we found that having the O-secretor phenotype was associated with a 2.3-fold increased odds of being a case (95% confidence interval, 1.2-4.4; P = 0.02).

Conclusions: The O-secretor mucin glycan phenotype is associated with susceptibility to asthma exacerbation. Clinical trial registered at www.clinicaltrials.gov (NCT00201266).

Figure 1.

Influence of secretor status on expression of the H antigen in airway epithelial cells. (A) Lectin staining for the H antigen in a subject with asthma with the O-secretor mucin phenotype shows strong expression in goblet cell mucins. (B) Lectin staining for the H antigen in an O nonsecretor phenotype shows absent expression in goblet cell mucins. In contrast, the H antigen is detectable in basal cells in secretors and nonsecretors, demonstrating that basal cells can synthesize the H antigen (presumably using an α1,2 fucosyltransferases encoded by FUT1 rather than FUT2).