Peripheral Vesicular-Bound Hla-g as Predictor of Graft Tolerance after Lung Transplantation

PurposeSurvival after lung transplantation (LTx) still remains limited by chronic lung allograft dysfunction (CLAD). Prior studies showed an association between graft cellular expression of the checkpoint HLA-G and acceptance, whereas conversely, soluble HLA-G (sHLA-G) in plasma/BAL was associated with acute rejection. We investigated whether plasma levels of extra-vesicular (EVs)-bound HLA-G could predict CLAD.MethodsWe used data for 79 LTx recipients from COLT (Cohort For Lung Transplantation) cohortwith ≥1 available blood samples at 6-, or 12-months post-Tx, all with a stable function within the 1st year. Among them, 41 developed subsequent CLAD (Group CLAD=33 BOS and 8 RAS) and 38 remained STABLE at 3 years. 20 heathy individuals (HI) were negative controls. EVs from plasma were isolated by size exclusion chromatography and characterized by nanoparticule tracking analysis. Plasma levels of EVs-bound HLA-G (sHLA-GEV) and of total soluble-HLA-G (sHLA-GTOT=sHLA-GEV + free sHLA-G) were measured by ELISA. Uni- and multivariate were performed to assess association of EVs levels and CLAD/survival.ResultsIn stable patients, mean plasma levels of sHLA-GEV at M6 and M12, were significantly increased as compared to those of HI (M6: 30.2 vs 15,1 ng/mL, p=0.008, and M12: 37.8 vs 15.1 ng/mL, p=0.0009, respectively). In BOS patients, a decreased plasma levels of sHLA-GEV were observed at M6 and M12 as compared to stable patients, with a significant difference at M12 (mean sHLA-GEV of 23.7 ng/mL vs 38.7 p=0.02). In those BOS patients, sHLA-GEV levels remained increased as compared to HI at M6 (p=0.01). In RAS patients, sHLA-GEV levels was similar to stable patients at M6 and M12, and increased as compared to HI (M12: 40,5 vs 15,6 ng/mL, p=0.004). Among the whole cohort, a higher freedom from CLAD was observed in patients with sHLA-GEV level > first IQR (=21.3 g/ml) at M12 post-LTx (p=0.01, Figure 1).ConclusionOur data suggest that an early decrease of sHLA-GEV levels after LTx may be predictive of subsequent CLAD onset. Survival after lung transplantation (LTx) still remains limited by chronic lung allograft dysfunction (CLAD). Prior studies showed an association between graft cellular expression of the checkpoint HLA-G and acceptance, whereas conversely, soluble HLA-G (sHLA-G) in plasma/BAL was associated with acute rejection. We investigated whether plasma levels of extra-vesicular (EVs)-bound HLA-G could predict CLAD. We used data for 79 LTx recipients from COLT (Cohort For Lung Transplantation) cohortwith ≥1 available blood samples at 6-, or 12-months post-Tx, all with a stable function within the 1st year. Among them, 41 developed subsequent CLAD (Group CLAD=33 BOS and 8 RAS) and 38 remained STABLE at 3 years. 20 heathy individuals (HI) were negative controls. EVs from plasma were isolated by size exclusion chromatography and characterized by nanoparticule tracking analysis. Plasma levels of EVs-bound HLA-G (sHLA-GEV) and of total soluble-HLA-G (sHLA-GTOT=sHLA-GEV + free sHLA-G) were measured by ELISA. Uni- and multivariate were performed to assess association of EVs levels and CLAD/survival. In stable patients, mean plasma levels of sHLA-GEV at M6 and M12, were significantly increased as compared to those of HI (M6: 30.2 vs 15,1 ng/mL, p=0.008, and M12: 37.8 vs 15.1 ng/mL, p=0.0009, respectively). In BOS patients, a decreased plasma levels of sHLA-GEV were observed at M6 and M12 as compared to stable patients, with a significant difference at M12 (mean sHLA-GEV of 23.7 ng/mL vs 38.7 p=0.02). In those BOS patients, sHLA-GEV levels remained increased as compared to HI at M6 (p=0.01). In RAS patients, sHLA-GEV levels was similar to stable patients at M6 and M12, and increased as compared to HI (M12: 40,5 vs 15,6 ng/mL, p=0.004). Among the whole cohort, a higher freedom from CLAD was observed in patients with sHLA-GEV level > first IQR (=21.3 g/ml) at M12 post-LTx (p=0.01, Figure 1). Our data suggest that an early decrease of sHLA-GEV levels after LTx may be predictive of subsequent CLAD onset.