Proteomic approaches for biomarker identification in chronic lung allograft dysfunction (CLAD) - 04/04/15
Résumé |
Introduction |
After lung transplantation (LT), survival is limited because of chronic lung allograft dysfunction (CLAD), an irreversible condition divided in 2 subtypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). As a part of SysCLAD, an EU-funded FP7 project, this study aimed to identify predictive biomarkers of CLAD onset 3years after LT, by analysing samples from COLT cohort, a French prospective cohort of lung transplant recipients, with 2 proteomic approaches.
Methods |
Broncho-alveolar lavage fluids (BAL) and plasmas withdrawn at month 6 and 12 after LT, in the 91 first patients of COLT cohort, were selected. iTRAQ-MALDI MS/MS analysis allowed protein identification and quantification after pooling samples according to patients’ phenotype. SELDI-TOF MS approach completed biomarker identification by analyzing individual proteomic profiles.
Results |
Among 148 and 135 proteins identified in BAL at month 6 and 12, 28 were differentially expressed between CLAD and stable patients. One potential biomarker could predict CLAD onset with a sensitivity of 73% and a specificity of 81%. In plasma, among 187 and 213 proteins identified, 11 proteins were differentially expressed in CLAD, mainly involved in proteolysis, inflammation, complement cascade, innate and humoral immunity.
Conclusion |
All results will be further validated and integrated into a predictive computational model of CLAD built with clinical and experimental data: environment, microbiome, immunological assays, omics.
Le texte complet de cet article est disponible en PDF.Keywords : Infection, Inflammation