0 avis
A large French genetic cohort to identify predictive molecular factors of chronic lung allograft dysfunction
Archive ouverte
Edité par CCSD -
International audience. Chronic respiratory diseases are among the leading causes of morbidity and mortality worldwide with 3.3 million deaths each year. For patients with end-stage lung disease, the only viable option is lung transplantation (LT). However, the lung graft survival remains limited with only 50.6% survival at 5 years post-transplantation mainly due to the development of chronic allograft dysfunction (CLAD). CLAD is defined by a >=20% decline in measured forced expiratory volume value from the reference and regroups 3 phenotypes: BOS (bronchiolitis obliterans syndrome) which is a predominantly obstructive ventilatory syndrome; RAS defined by a restrictive pattern; and a mixed obstructive and restrictive pattern. There is therefore an essential need for better understanding the molecular mechanisms involved in the CLAD phenotypes pathophysiology. COLT is a French cohort of LT created in 2009 in Nantes, which has included 2,117 patients from 9 transplant centers (Nantes, Bordeaux, Lyon, Paris, Marseille, Strasbourg, Grenoble, Toulouse and Suresnes). To supplement the rich clinical data collected for COLT (donor and recipient demographics and medical history, transplantation follow-up), we genotyped a subset of 392 LT donor-recipient pairs with the Affymetrix Axiom PRMA microarray (900K SNPs). Our genetic cohort represents an accurate snapshot of the entire COLT cohort as no variables (e.g. age, sex, initial respiratory disease, survival rate) significantly diverge from the global cohort (P>0.05). Overall, 54% were male, mean age at transplant was 47, the mean follow-up was 41 months and the mean survival rate was 3 years. We have built one of the largest genetic cohorts dedicated to LT comprising both donor and recipient large-scale genotypes. The integration of clinical phenotypes with genetic data will empower us to investigate HLA and non-HLA factors involved in CLAD phenotypes in the near future in order to improve the management and survival of lung transplanted patients.
Consulter en ligne
Suggestions
Du même auteur
