Late Breaking Abstract - Prediction of chronic lung allograft rejection (CLAD) by measurement of peripheral T cells linked to the inhibitory check-point HLA-G

Background: Long-term survival after lung transplantation (LTx) still remains limited because of chronic lung allograft dysfunction (CLAD) and better understanding of operational tolerance is needed. Methods: We aimed to investigate the role of the inhibitory checkpoint HLA-G expressed by different peripheral cell populations in predicting CLAD development. Data from COLT cohort (follow-up>3 years post-LTx) were investigated. Analysis by cytometry, focused on HLA-G and other markers, were performed. T-cell populations at different Time-points and their kinetics (1-12months T-cells ratio) were compared between Stable and CLAD. Results: The study included 150 patients (78 stable and 72 CLAD). Freedom from CLAD was lower in patients with 1-12 months CD4+specific/HLA-G-linked T-cells (CD4+spe/HLA-G T cells) ratio >2.64 than in patients with ratio 0.069% (Log-rank,p=0.04). On multivariable analysis: 1) increase of 1-12mo CD4+spe/HLA-G T-cell ratio was an independent predictor of CLAD (HR=1.25;95%CI,1.09-1.44;p=0.001). 2) increase of %CD4+CD25+CD127low T cells (%CD4+T cells) was also an independent predictor of graft failure ((HR=1.1;95%CI,1.00-1.30;p=0.01). Conclusion: Our data suggest that CD4+specific/HLA-G-linked T cells appear as a contributor to graft unstability and as a new predictor of CLAD onset.