Blood MMP-9 measured at 2 years after lung transplantation as a prognostic biomarker of chronic lung allograft dysfunction
Authors: 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 ,   the COLT consortium, Blanchard Elodie , Demant Xavier , Hulo Virginie , Ruiz-Patino Maria , Kuylen Maarten Vander , Sokolow Youri , Stefanidis Constantin , Huybrechts Isabelle , Perrin Laurent , Taccone Fabio , Etienne Isabelle , Knoop Christiane , Roussoulières Anna , Hites Maya , Lambert Agnes , Hemelsoet Axelle , Bedouch Pierrick , Briault Amandine , Falque Loic , Perrier Quentin , Raymond Christel Saint , Chacaroun Samarmar , Gioria Yoann , Quentin Joane , Grima Renaud , Drevet Gabrielle , Maury Jean-Michel , Tronc François , Portan Philippe , Mornex Jean-François , Du Vignaud Claire Merveilleux , Chatron Eva , Glérant Jean Charles , Turquier Ségolène , Mohamed Salim Si , Cottin Vincent , Chalabresse Lara , Dubois Chantal , Rea Aurélie , Reignier Médéric , Canterini Julia , Carlier Nicolas , Boussaud Véronique , Guillemain Romain , D’Journo Xavier-Benoit , Thomas Pascale-Alexandre , Trousse Delphine , Brioude Geoffrey , Boulate David , Fourdrain Alex , Bregeon Fabienne , Delliaux Stéphane , Reynaud-Gaubert Martine , Coltey Bérengère , Dufeu Nadine , Coiffard Benjamin , Bermudez Julien , Nieves Ana , Dutau Hervé , Tronchetti Julie , Gaubert Jean-Yves , Habert Paul , Di Biscéglie Mathieu , Basire Agnes , Pedini Pascal , Daviet Florence , Guervilly Christophe , Hraiech Sami , Forel Jean Marie , Delamarre Louis , Charvet Aude , Gragueb-Chatti Ines , Mora Pierre , Laurent Daniel , Giusiano Sophie , Dales Jean-Philippe , Gaubert Mélanie , Laine Marc , Lacoste Philippe , Perigaud Christian , Roussel Jean-Christian , Senage Thomas , Mugniot Antoine , Danner Isabelle , Tissot Adrien , Bry Charlotte , Penhouet Morgane , Eschapasse Emmanuelle , Horeau-Langlard Delphine , Blanc François-Xavier , Lepoivre Thierry , Vourch Mickael , Brouard Sophie , Danger Richard , Bernard Megguy , Godard Elodie , Valéro Régine , Maugendre Karine , Durand Eugénie , Yeremenko Nataliya , Foureau Aurore , Lair David , Gallot Géraldine , Berthome Mathilde , Le Pavec Jérôme , Dauriat Gaëlle , Pradere Pauline , Feuillet Séverine , Dolidon Samuel , Medraoui Chahine , Gazengel Pierre , Crutu Adrian , Hanna Amir , Fabre Elie , Mercier Olaf , Mitilian Delphine , Issard Justin , Fabre Dominique , Castier Yves , Mordant Pierre , Cerceau Pierre , Girault Antoine , Roussel Arnaud , Atchade-Thierry Enora , Jean-Baptiste Sylvain , Boudinet Sandrine , Tanaka Sébastien , Gouel Aurélie , Montravers Philippe , Zappella Nathalie , Snauwaert Aurélie , Tashk Parvine , Lortat-Jacob Brice , Goletto Tiphaine , Mouren Domitille , Morer Lise , Salpin Mathilde , Mal Hervé , Marceau Armelle , Weisenburger Gaëlle , Bunel Vincent , Sandot Adèle , El Husseini Kinan , Halitim Pierre , Genet Lucie , Trigueiros Sabrina , Savary Alice , Rabia Hakima , Falcoz Pierre-Emmanuel , Olland Anne , Ponte Charlotte , Tacquard Charles , Ajob Garib , Collange Olivier , Pons Antoine , Delabranche Xavier , Helms Olivier , Roche Anne , Renaud-Picard Benjamin , Kessler Romain , Degot Tristan , Hirschi Sandrine , Schuller Armelle , Dory Anne , Toti Florence , Benkirane-Jessel Nadia , Kessler Laurence , Stauder Julien , Sage Edouard , Parquin Francois , De Miranda Sandra , Picard Clément , Roux Antoine , Brugière Olivier , D’Urso Béatrice , Stern Marc , Mbarka Akounach , Magnan Antoine , Marquant Quentin , Schwartz Isabelle , Salvator Helene , Pascreau Tiffany , Villeneuve Thomas , Dupuis Marion , Murris-Espin Marlène , Rabinel Pierre , Brouchet Laurent , Crognier Laure , Mathe Olivier , Legenne Frédérique , Barthes Myriam , Vilquin Blandine , Costes Anne-Laure , Recoche Isabelle , Bergeron Anne , Berra Gregory , Koutsokera Angela 
Published: February 2024

Abstract
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.