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Whole blood gene expression from lung transplanted patients with chronic lung allograft dysfunction

ABSTRACT: Chronic lung allograft dysfunction (CLAD) limits the long term survival after lung transplantation. CLAD is diagnosed late on the decline in lung function, when any immuno-intervention is ineffective. Identification of early forerunners of CLAD is therefore essential to prevent the progression of the disease before irreversible damages to the allograft. We used large-scale gene expression profiling of whole blood cells to identify early biomarkers of Bronchiolitis Obliterans Syndrome (BOS), the main form of CLAD. Microarray experiments performed from 80 patients (40 stable (STA) and 40 BOS) identify 47 genes differentially expressed between STA and BOS recipients. An independent set of patients (13 STA, 11 BOS) was then used for external validation by qPCR. POU Class 2 Associating Factor 1 (POU2AF1), T-cell leukemia/lymphoma protein 1A (TCL1A) and B-cell lymphocyte kinase (BLK) genes were identified and validated as predictive markers of BOS more than 6 months before diagnosis with AUCs of 0.83, 0.77 and 0.78 respectively. These genes allow stratifying upon CLAD risk (log-rank test p<0.01) and could provide clinicians with new tools to improve follow-up and adapt treatment of patients likely to develop BOS.

ORGANISM(S): Homo sapiens

PROVIDER: GSE94557 | GEO | 2018/02/23

REPOSITORIES: GEO

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Project description:Background: Mesenchymal stromal cells (MSC) have been proposed as a future cell based therapy for lung diseases like bronchiolitis obliterans syndrome (BOS). Theoretically, it might be beneficial to use lung resident MSC already adapted to the pulmonary environment. We therefore aimed to compare lung MSC with the well-characterized bone marrow MSC. Furthermore, MSC isolated from lung-transplanted patients with BOS were compared to MSC isolated from good outcome recipients. Methods: MSC were isolated from bone marrow (BM) and adult/fetal lung tissues and compared by a comprehensive panel of assays. Results:The gene expression profiles of adult lung derived and fetal lung derived MSC were very similar compared to BM derived MSC, with only 235 and 338 genes, respectively, being significantly differently expressed. Out of the 235 genes that were significantly different between adult lung derived and BM derived MSC, 90 genes were higher expressed in the lung derived MSC. In case of fetal lung derived MSC, 166 genes were higher expressed compared to the BM derived MSC. Interestingly, only, 89 genes were found to be expressed differently when comparing BM derived MSC to both, fetal and adult lung derived MSC, indicating that these genes are lung specific. Next, we went on to evaluate if MSC isolated from biopsies of lung-transplanted patients with BOS differed compared to patients without BOS, i.e. good outcome recipients. Here we found that four genes (Sox9, FAR2, LOC728855 and NDUFS5) were significantly higher expressed in MSC isolated from BOS patients Conclusions: This data demonstrates that lung resident MSC possess lung specific properties that should be taken into considerations when using MSC for cell-based therapy in severe lung disorders like BOS. These results also show that MSC isolated from lung-transplanted patients with BOS do not have an altered phenotype. Comparison of gene expression of MSC isolated from bone marrow, adult lung and fetal lung.

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Whole blood gene expression from lung transplanted patients with chronic lung allograft dysfunction

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