Proteomic approaches for biomarker identification in chronic lung allograft dysfunction (CLAD)

Abstract

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 3 years 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 Methods Broncho-alveolar lavage fluids (BAL) and plasmas withdrawn at month 6 and 12 after LT, in the 91 first patients of COLT cohort, were selected.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.