The SysCLAD- Systems Prediction of Chronic Lung Allograft Dysfunction Study: Aims, Strategy and First Data

Abstract

Purpose The SysCLAD study is an European Union-funded project under the FP-7 to predict CLAD signature by year-1 post lung transplantation (LT) before any decline in lung function. CLAD and its subtypes Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome represent the actual limitation resulting in a high morbi-mortality and costs. Specific aims of SysCLAD are identification of CLAD biomarkers, a better understanding of CLAD mechanisms and a predictive and personalized signature of CLAD. Methods and Materials Built upon a cohort of LT recipients already transplanted and recruited since September 2009 in 14 LT centres, SysCLAD signature will be based on a mathematical model developed through a systems medicine approach integrating clinical and biological data collected within the first year post LT in 2 steps, using calibration and validation samples within LT cohort. Clinical data include donors and recipients characteristics and post LT clinical events; biological data donors and recipients HLA, whole blood transcriptomics, BAL and blood proteomics at months 6 and 12, together with once miRNA, BAL microbiote and recipient genetic polymorphisms analysis at month 6. Results By November 2012, 820 LT candidates of whom 652 received a LT; indications were by digressive order CF, COPD/emphysema, IPF, PH, bronchiectasis and others; LT recipients were 42.7 ± 15.2 yrs old, 320 received a double LT; 2-years survival was 76%. In SysCLAD biobank, they are by year-1 post LT to predict besides “clinicome”: 1 152 TBB, 7 537 PBMC aliquots, 2362 BAL, 1311 blood samples for transcriptomics Paxgene®, 12 903 plasma and 11 008 sera aliquots. Conclusions CLAD tool is expected by early personalized interventions to improve morbi-mortality and increase the cost-effectiveness of LT. Funds from PHRC 2008 and Vaincre La Mucoviscidose within the 11 French lung Transplantation centres to launch Cohort in Lung Transplantation (COLT)-ClinicalTrials.gov Identifier: NCT00980967, Programme transplantation 2008, PRTP-13, and #HEALTH-F5-2012-305457, a FP-7 call.