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

Mottais, Angélique;Qiu, Ziyu;Detry, Bruno;Lecocq, Marylène;Gohy, Sophie;et.al.
(2025) ERJ Open Research — p. 01369-02024 (2025)

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Background: In the era of highly effective modulator therapies (HEMTs), pulmonary function, the number and severity of exacerbations and the quality of life of people with cystic fibrosis (pwCF) 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 pwCF before and after elexacaftor/tezacaftor/ivacaftor (ETI) initiation, and 2) to investigate the mucosal IgA response in urine from pwCF compared with healthy controls (CTRL). Methods: We quantified by ELISA the different agents comprising the pIgR/IgA system (total IgA, IgA1, IgA2, secretory IgA (S-IgA), secretory component (SC) of pIgR, and specific IgA against Pseudomonas aeruginosa (Pa) or against staphylococcal enterotoxin B (SEB) in sputum, serum, and urine from 57 pwCF and 30 healthy controls (CTRL). Results: Hyperactivation of the pIgR/IgA system was maintained under ETI, with no significant differences between total IgA, IgA1, IgA2, S-IgA nor SC levels in sputum, serum and urine from pwCF 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 pwCF, with a higher level of total IgA (p=0.0141) compared with CTRL. Conclusion: Even with HEMT, the pIgR/IgA system remains hyperactivated after at least three months of treatment, suggesting that at this time the local IgA immunity is always impaired.
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Mottais, A., Qiu, Z., Detry, B., Lecocq, M., Goubau, C., Berardis, S., Hox, V., Froidure, A., Pilette, C., & Gohy, S. (2025). Immunoglobulin A mucosal immunity in people with cystic fibrosis shortly after initiation of highly effective modulator therapy. ERJ Open Research, 01369-02024. https://doi.org/10.1183/23120541.01369-2024 (Original work published 2025)