Long-term survival after lung transplantation (LT) is hampered by the occurrence of chronic lung allograft dysfunction (CLAD), either as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). BOS may be triggered by several factors, e.g. recurrent post-transplant infections [1Verleden G.M., Glanville A.R., Lease E.D., Fisher A.J., Calabrese F., Corris P.A., e al. Chronic lung allograft dysfunction: definition, diagnostic criteria, and approaches to treatment-A consensus report from the Pulmonary Council of the ISHLT J Heart Lung Transplant 2019 ;  38 : 493-503 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti]. As immunoglobulin (Ig) A is key for mucosal immune defence against infections and for controlling the microbial load [2de Fays C., Carlier F.M., Gohy S., Pilette C. Secretory Immunoglobulin A immunity in chronic obstructive respiratory diseases Cells 2022 ;  11 : 1324 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti], this study 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 (COLT) were collected at pre-defined timepoints after LT, and prior to the diagnosis of BOS (pre-BOS, n=30) compared with BOS-free patients (n=30). BAL were assessed for secretory (S)-IgA, and sera were assessed for IgA, S-IgA and secretory component (SC, released by pIgR cleavage). Additionally, pIgR expression in the bronchiolar epithelium 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).

S-IgA levels were reduced in BAL from pre-BOS LT recipients versus BOS-free (Fig. 1A; 16.1 vs. 33.4μg/mL, P<0.01). Serum IgA levels were similar across the 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). Bronchiolar pIgR expression was reduced in BOS (Fig. 1D-E; P<0.05 vs. BOS-free and pre-BOS), with further decrease in end-stage BOS (P<0.0001 vs. BOS-free and pre-BOS).

These results suggest that the epithelial, secretory IgA system is impaired in BOS, this alteration being present prior to the functional diagnosis of CLAD. Increased levels of S-IgA and SC in serum in pre-BOS may reflect a spill-over from the lung, reflecting hyperpermeability of the airway barrier. This mucosal IgA defect could contribute to BOS pathogenesis by reducing immune exclusion of auto/alloantigens, and subsequently increasing local immune triggers, including recurrent infections.