Impaired pIgR/S-IgA mucosal immunity in bronchiolitis obliterans syndrome.
(2022) Journées de Recherche Respiratoire 2022 — Location: Reims (14.October.2022)
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- Aims. Long-term survival after lung transplantation (LT) is hampered by the occurrence of chronic lung allograft dysfunction (CLAD). CLAD may manifest as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS), and may be triggered by several factors, e.g. recurrent post-transplant infections (1). As immunoglobulin (Ig) A is crucial to ensure mucosal immunity and limit airway microbial load(2), we explored whether IgA and its epithelial receptor, the polymeric Ig receptor (pIgR) are impaired in BOS. Methods. Bronchoalveolar lavages (BAL, n=120) and sera (n=179) from LT recipients included in the Cohort for Lung Transplantation (COLT) were collected at pre-defined timepoints after LT, and prior to the diagnosis of functional stability (BOS-free, n=30) or BOS (pre-BOS, n=30). BAL were assessed for secretory (S)-IgA, while sera were assessed for IgA, S-IgA and secretory component (SC, released by pIgR apical cleavage following transcytosis). pIgR expression at the bronchiolar epithelium pIgR level was quantified in transbronchial biopsies from BOS-free (n=20), pre-BOS (n=19) and BOS LT recipients (n=12), as well as in end-stage BOS explants (n=15). Results. S-IgA levels were reduced in BAL from pre-BOS LT recipients versus BOS-free (Fig 1A; 16.1 vs 33.4 µg/ml, p<0.01). Serum IgA levels were similar across the studied groups, while both SC and S-IgA were increased in pre-BOS LT recipients (Fig 1B-C; S-IgA: 40.6 vs 21.2µg/ml, p<0.05; SC: 156.0 vs 97.2ng/ml, p<0.001). pIgR bronchiolar expression was reduced in transbronchial biopsies from BOS (Fig 1D-E; p<0.05 vs BOS-free and pre-BOS), with further decrease in end-stage BOS explants (p<0.0001 vs BOS-free and pre-BOS). Conclusions. BAL S-IgA and pIgR decreased levels suggest that the pIgR/IgA system is impaired in BOS. This alteration is even present prior to the functional diagnosis of CLAD. Serum SC and S-IgA increased levels in pre-BOS LT recipients may reflect a spill-over from bronchoalveolar fluids, witnessing an permeability of the respiratory barrier. These features could play a pathogenic role by increasing susceptibility to local infections.
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Carlier, F., & et al. (2022). Impaired pIgR/S-IgA mucosal immunity in bronchiolitis obliterans syndrome. Journées de Recherche Respiratoire 2022, Reims. https://hdl.handle.net/2078.5/104226