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

肺移植后 2 年测量血液 MMP-9 作为慢性肺移植功能障碍的预后生物标志物

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

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

Conclusion

Plasmatic MMP-9 levels measured 2 years after lung transplantation have prognostic value for CLAD.

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%.

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