[HTML][HTML] Gene expression profiling of bronchoalveolar lavage cells preceding a clinical diagnosis of chronic lung allograft dysfunction

SS Weigt, X Wang, V Palchevskiy, AL Gregson… - PloS one, 2017 - journals.plos.org
SS Weigt, X Wang, V Palchevskiy, AL Gregson, N Patel, A DerHovanessian, MY Shino…
PloS one, 2017journals.plos.org
Background Chronic Lung Allograft Dysfunction (CLAD) is the main limitation to long-term
survival after lung transplantation. Although CLAD is usually not responsive to treatment,
earlier identification may improve treatment prospects. Methods In a nested case control
study, 1-year post transplant surveillance bronchoalveolar lavage (BAL) fluid samples were
obtained from incipient CLAD (n= 9) and CLAD free (n= 8) lung transplant recipients.
Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free …
Background
Chronic Lung Allograft Dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects.
Methods
In a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL) fluid samples were obtained from incipient CLAD (n = 9) and CLAD free (n = 8) lung transplant recipients. Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free from CLAD for at least 4 years following bronchoscopy. Transcription profiles in the BAL cell pellets were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression analysis, based on an absolute fold change (incipient CLAD vs no CLAD) >2.0 and an unadjusted p-value ≤0.05, generated a candidate list containing 55 differentially expressed probe sets (51 up-regulated, 4 down-regulated).
Results
The cell pellets in incipient CLAD cases were skewed toward immune response pathways, dominated by genes related to recruitment, retention, activation and proliferation of cytotoxic lymphocytes (CD8+ T-cells and natural killer cells). Both hierarchical clustering and a supervised machine learning tool were able to correctly categorize most samples (82.3% and 94.1% respectively) into incipient CLAD and CLAD-free categories.
Conclusions
These findings suggest that a pathobiology, similar to AR, precedes a clinical diagnosis of CLAD. A larger prospective investigation of the BAL cell pellet transcriptome as a biomarker for CLAD risk stratification is warranted.
PLOS