Carlier, F.M., Pretolani, M., Detry, B., Planté-Bordeneuve, T., Longchampt, E., Falque, L., Reynaud-Gobert, M., Hirschi, S., Demant, X., Mornex, J., Tissot, A., Pavec, J. Le, Bunel-Gourdy, V., Foureau, A., Vallée, A., Pilette, C., and Brugière, O.
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 is triggered by several factors, e.g. post-transplant infections. As immunoglobulin (Ig) A is crucial to ensure mucosal immunity and limit airway microbial load, we explored whether IgA and its epithelial receptor, the polymeric Ig receptor (pIgR) are impaired in BOS. Bronchoalveolar lavages (BAL, n=120) and sera (n=179) from LT recipients included in the Cohort for Lung Transplantation were collected at defined timepoints after LT, prior to the diagnosis of functional stability (BOS-free, n=30) or BOS (pre-BOS, n=30). BAL were assessed for secretory (S)-IgA. Sera were assessed for IgA, S-IgA and secretory component (SC, released by pIgR apical cleavage after transcytosis). pIgR epithelial expression 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). BAL S-IgA was reduced in pre-BOS LT recipients (Fig. 1A, 16.1 vs 33.4 µg/ml, p<0.01). Serum IgA was reduced after LT, with no difference across the groups. In contrast, serum 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). BAL S-IgA and pIgR decreased levels suggest that the pIgR/IgA system is impaired in BOS. This alteration is present prior to the functional diagnosis of CLAD. Serum SC and S-IgA increased levels in pre-BOS 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. [ABSTRACT FROM AUTHOR]