Blood MMP-9 measured at 2 years after lung transplantation as a prognostic biomarker of chronic lung allograft dysfunction

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Tissot, Adrien | Durand, Eugénie | Goronflot, Thomas | Coiffard, Benjamin | Renaud-Picard, Benjamin | Roux, Antoine | Demant, Xavier | Mornex, Jean-François | Falque, Loïc | Salpin, Mathilde | Le Pavec, Jérôme | Villeneuve, Thomas | Boussaud, Véronique | Knoop, Christiane | Magnan, Antoine | Lair, David | Berthelot, Laureline | Danger, Richard | Brouard, Sophie

Edité par CCSD ; BioMed Central -

International audience. Background : Long-term outcomes of lung transplantation (LTx) remain hampered by chronic lung allograft dysfunction (CLAD). Matrix metalloproteinase 9 (MMP-9) is a secretory endopeptidase identified as a key mediator in fibrosis processes associated with CLAD. The objective of this study was to investigate whether plasma MMP9 levels may be prognostic of CLAD development. Methods : Participants were selected from the Cohort in Lung Transplantation (COLT) for which a biocollection was associated. We considered two time points, year 1 (Y1) and year 2 (Y2) post-transplantation, for plasma MMP-9 measurements. We analysed stable recipients at those time points, comparing those who would develop a CLAD within the 2 years following the measurement to those who would remain stable 2 years after. Results : MMP-9 levels at Y1 were not significantly different between the CLAD and stable groups (230 ng/ml vs. 160 ng/ml, p = 0.4). For the Y2 analysis, 129 recipients were included, of whom 50 developed CLAD within 2 years and 79 remained stable within 2 years. MMP-9 plasma median concentrations were higher in recipients who then developed CLAD than in the stable group (230 ng/ml vs. 118 ng/ml, p = 0.003). In the multivariate analysis, the Y2 MMP-9 level was independently associated with CLAD, with an average increase of 150 ng/ml (95% CI [0–253], p = 0.05) compared to that in the stable group. The Y2 ROC curve revealed a discriminating capacity of blood MMP-9 with an area under the curve of 66%. Conclusion : Plasmatic MMP-9 levels measured 2 years after lung transplantation have prognostic value for CLAD.

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