Work

Immunoglobulin A mucosal immunity in people with cystic fibrosis shortly after initiation of highly effective modulator therapy

Year: 2025

Type: article

Abstract: Background: In the era of highly effective modulator therapies, pulmonary function, the number and severity of exacerbations and the quality of life of people with cystic fibrosis (CF) are improving significantly. The polymeric immunoglobulin receptor (pIgR)/IgA system, which is impaired in CF, protects the respiratory epithelium against harmful inhaled pathogens. The aims of this interventional prospective study were 1) to assess IgA mucosal immunity in bodily fluids from people with CF before and after elexacaftor/tezacaftor/ivacaftor (ETI) initiation, and 2) to investigate the mucosal IgA response in urine from people with CF compared with healthy controls. Methods: or against staphylococcal enterotoxin B in sputum, serum, and urine from 57 people with CF and 30 healthy controls. Results: Hyperactivation of the pIgR/IgA system was maintained under ETI, with no significant differences between total IgA, IgA1, IgA2, S-IgA nor secretory component levels in sputum, serum and urine from people with CF before and after ETI initiation, except for an increase in urine S-IgA after treatment. We demonstrate an activation of the mucosal immune system in the urinary tract of people with CF, with a higher level of total IgA (p=0.0141) compared with healthy controls. Conclusion: Even with highly effective modulator therapy, the pIgR/IgA system remains hyperactivated after ≥3 months of treatment, suggesting that at this time the local IgA immunity is always impaired.

Source: ERJ Open Research

DOI: 10.1183/23120541.01369-2024