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Altered pIgR/IgA mucosal immunity in bronchiolitis obliterans syndrome - 17/02/23

Doi : 10.1016/j.rmr.2022.11.047 
F. Carlier 1, 2, 3, 4, , M. Pretolani 4, B. Detry 1, N. Heddebaut 4, T. Planté-Bordeneuve 1, E. Longchampt 5, L. Falque 6, M. Reynaud-Gaubert 7, S. Hirschi 8, X. Demant 9, J. Mornex 10, A. Tissot 11, J. Le Pavec 12, J. Messika 13, A. Foureau 11, A. Vallée 14, C. Pilette 1, 15, O. Brugière 16
1 Institut de recherche expérimentale et clinique (pôle pneumologie, ORL et dermatologie), UCLouvain, Bruxelles, Belgium 
2 Centre de transplantation pulmonaire, CHU UCL Namur, Yvoir, Belgium 
3 Service de pneumologie, CHU UCL Namur, Yvoir, Belgium 
4 Unité de recherche Inserm U1152, université Paris-Descartes, Paris, France 
5 Service d’anatomie pathologique, hôpital Foch, Suresnes, France 
6 Service de pneumologie et transplantation pulmonaire, CHU de Grenoble, Grenoble, France 
7 Service de pneumologie et transplantation pulmonaire, CHU de Marseille, Marseille, France 
8 Service de pneumologie et transplantation pulmonaire, CHU de Strasbourg, Strasbourg, France 
9 Service de pneumologie et transplantation pulmonaire, CHU de Bordeaux, Bordeaux, France 
10 Service de pneumologie et transplantation pulmonaire, CHU de Lyon, Lyon, France 
11 Service de pneumologie et transplantation pulmonaire, CHU de Nantes, Nantes, France 
12 Service de pneumologie et transplantation pulmonaire, centre chirurgical Marie-Lannelongue, Le Plessis-Robinson, France 
13 Service de pneumologie B et transplantation pulmonaire, hôpital Bichat (AP–HP), Paris, France 
14 Département de biostatistiques – DRCI, Hôpital Foch, Suresnes, France 
15 Service de pneumologie, cliniques universitaires Saint-Luc, Bruxelles, Belgium 
16 Service de pneumologie et transplantation pulmonaire, hôpital Foch, Suresnes, France 

Corresponding author.

Resumen

Introduction

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 [1]. As immunoglobulin (Ig) A is key for mucosal immune defence against infections and for controlling the microbial load [2], this study 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 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).

Results

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).

Conclusion

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.

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© 2022  Publicado por Elsevier Masson SAS.
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P. 132-133 - février 2023 Regresar al número
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