[en] [en] BACKGROUND: There is a pressing need to identify early biomarkers of lung involvement in systemic sclerosis (SSc) to start as soon as possible antifibrotic therapy. We aimed to identify extracellular vesicle-derived microRNAs (EV-miRNAs) that are differentially expressed between SSc patients with and without interstitial lung disease (ILD), explore their diagnostic value and investigate their functional properties.
METHODS: Small EVs (sEVs) derived from plasma were isolated from 91 well-characterised SSc patients with ILD (SSc-ILD, n=45), without ILD (SSc-no ILD, n=46) and 43 matched healthy subjects (HS). Small RNA sequencing followed by quantitative RT-PCR were used to identify and validate sEV-miRNAs associated to SSc-ILD. Correlations between SSc-ILD-associated miRNAs and clinical parameters were assessed, as well as the impact of related miRNAs/sEVs on fibrosis.
RESULTS: We identified a 4-miRNA signature associated with ILD in SSc context (miR-584-5p, miR-744-5p, miR-1307-3p and miR-10b-5p) (ROC AUC=0.85, 95% CI 0.76-0.94, p<0.0001). Deeper analysis revealed a correlation of these candidates with pulmonary function tests (DLCO and FVC), highlighting their capacity to monitor lung fibrosis progression in SSc patients. Furthermore, SSc-ILD-associated sEV miRNAs are positively correlated and enriched in circulating lymphocytes, suggesting that these immune cells are their cellular source. Finally, functional studies highlighted an alteration of functional properties of sEVs in SSc-ILD context mainly due to the transfer of profibrotic miR-584-5p in lung fibroblasts.
CONCLUSIONS: Our sEV-based biomarker approach enabled to identify a promising 4-miRNA signature characteristic of ILD in SSc patients. Furthermore, the profibrotic properties of SSc-ILD-associated sEVs suggest a prominent role of these vesicles on SSc severity.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Guiot, Julien ; Université de Liège - ULiège > Département des sciences cliniques > Pneumologie - Allergologie
André, Béatrice ; Université de Liège - ULiège > Département des sciences cliniques
Potjewijd, Judith ; Department of Internal Medicine, Division Clinical and Experimental Immunology, Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
JACQUERIE, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > > Service de rhumatologie
Cremers, Sébastien ; Université de Liège - ULiège > Département des sciences cliniques > Pneumologie - Allergologie
Henket, Monique ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Idoufkir, Latifa ; Université de Liège - ULiège > Département des sciences cliniques > Pneumologie - Allergologie
Remacle, Claire ; Université de Liège - ULiège > Département des sciences de la vie
Tobal, Rachid; Department of Internal Medicine, Division Clinical and Experimental Immunology, Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
GILTAY, Laurie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
GESTER, Fanny ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Polese, Barbara ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Hamaïdia, Malik ; Université de Liège - ULiège > Département GxABT > Microbial technologies
Struman, Ingrid ; Université de Liège - ULiège > GIGA > GIGA Cancer - Molecular Angiogenesis
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Malaise, Michel ; Université de Liège - ULiège > Département des sciences cliniques
de Seny, Dominique ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
van Paassen, Pieter; Department of Internal Medicine, Division Clinical and Experimental Immunology, Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
Louis, Renaud ; Université de Liège - ULiège > Département des sciences cliniques > Pneumologie - Allergologie
Ribbens, Clio ; Université de Liège - ULiège > Département des sciences cliniques > Rhumatologie
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