Circulating Vesicular-bound HLA-G as Noninvasive Predictive Biomarker of CLAD After Lung Transplantation
Year: 2024
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Circulating extracellular vesicles (EVs) have shown promising results as noninvasive biomarkers for predicting disease outcomes in solid organ transplantation. Because in situ graft cell expression of the tolerogenic molecule HLA-G is associated with acceptance after lung transplantation (LTx), we hypothesized that plasma EV-bound HLA-G (HLA-G EV ) levels could predict chronic lung allograft dysfunction (CLAD) development. METHODS: We analyzed 78 LTx recipients from the Cohort-for-Lung-Transplantation cohort, all in a stable (STA) state within the first year post-LTx. At 3 y, 41 patients remained STA, and 37 had CLAD (bronchiolitis obliterans syndrome, BOS, [n = 32] or restrictive allograft syndrome [n = 5]). HLA-G EV plasma levels were measured at month 6 (M6) and M12 in 78 patients. CLAD occurrence and graft failure at 3 y post-LTx were assessed according to early HLA-G EV plasma levels. RESULTS: In patients with subsequent BOS, (1) HLA-G EV levels at M12 were significantly lower than those in STA patients ( P = 0.013) and (2) also significantly lower than their previous levels at M6 ( P = 0.04).A lower incidence of CLAD and BOS and higher graft survival at 3 y were observed in patients with high HLA-G EV plasma levels at M12 (high versus low HLA-G EVs patients [cutoff 21.3 ng/mL]: freedom from CLAD, P = 0.002; freedom from BOS, P < 0.001; and graft survival, P = 0.04, [log-rank]). Furthermore, in multivariate analyses, low HLA-G EV levels at M12 were independently associated with a subsequent risk of CLAD, BOS, and graft failure at 3 y ( P = 0.015, P = 0.036, and P = 0.026, respectively [Cox models]). CONCLUSIONS: This exploratory study suggests the potential of EV-bound HLA-G plasma levels as a liquid biopsy in predicting CLAD/BOS onset and subsequent graft failure.
Source: Transplantation
Authors: Olivier Brugière, Dora Dreyfuss, Ronan Guilet, Sophie Rong, Sandrine Hirschi, Benjamin Renaud-Picard, Martine Reynaud-Gaubert, Benjamin Coiffard, Vincent Bunel, Jonathan Messika, Xavier Demant, Jérôme Le Pavec, Gaelle Dauriat, Christel Saint Raymond, Loic Falque, Jean-Francois Mornex, Adrien Tissot, David Lair, Aurelie Le Borgne Krams, Veronique Bousseau, Antoine Magnan, Clément Picard, Antoine Roux, Matthieu Glorion, Maryvonick Carmagnat, Florence Gazeau, Kelly Aubertin, Edgardo Carosella, Alexandre Vallée, Cecile Landais, Nathalie Rouas-Freiss, Joel LeMaoult
Institutions: Université Paris Cité, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Hôpital Saint-Louis, Hôpital Foch, HIPI - Immunologie humaine, physiopathologie et immunithérapie, Institut de recherche Saint-Louis, Institut de biologie François Jacob, Service de Recherches en Hémato-Immunologie, Inserm, Regenerative NanoMedicine, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Assistance Publique Hôpitaux de Marseille, Assistance Publique – Hôpitaux de Paris, Hôpital Bichat-Claude-Bernard, Centre Hospitalier Universitaire de Bordeaux, Hôpital Marie Lannelongue, Centre Hospitalier Universitaire de Grenoble, Lyon 1 Université, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Hospices Civils de Lyon, Centre Hospitalier Universitaire de Nantes, Institut du Thorax, Center for Research in Transplantation and Translational Immunology, Université de Nantes, Nantes Université, Centre Hospitalier Universitaire de Toulouse, Hôpital Européen Georges-Pompidou, Centre National de la Recherche Scientifique, Laboratoire Matière et Systèmes Complexes
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4402658036