TY - JOUR
T1 - Serum miRNAs as potential biomarkers for the bronchiolitis obliterans syndrome after lung transplantation
AU - Budding, K
AU - Rossato, M
AU - van de Graaf, E A
AU - Kwakkel-van Erp, J M
AU - Radstake, T R D J
AU - Otten, H G
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/6
Y1 - 2017/6
N2 - Lung transplantation (LTx) is the last treatment for patients suffering from end-stage lung diseases. Survival post-LTx is hampered by the development of the bronchiolitis obliterans syndrome (BOS) and diagnosis is often late. Given the urgent clinical need to recognize BOS patients at an early stage, we analyzed circulating miRNAs to identify possible stratification markers for BOS development post-transplantation. Therefore, pro-fibrotic (miR-21, miR-155), anti-fibrotic (miR-29a) and fibrosis-unrelated (miR-103, miR-191) miRNAs were analyzed in serum of end-stage lung disease patients and during LTx follow-up. Significant elevated levels of serum miRNAs were observed for all investigated miRNAs in both chronic obstructive pulmonary disease and interstitial lung disease patients compared to healthy controls. The same miRNAs were also significantly increased in the serum of BOS+ vs. BOS- patients. Most importantly, miR-21, miR-29a, miR-103, and miR-191 levels were significantly higher in BOS+ patients prior to clinical BOS diagnosis. We demonstrated that a selected group of miRNAs investigated is elevated in end-stage lung disease and BOS+ patients, prior to clinical BOS diagnosis. Even if further research is expedient on the prognostic value of circulating miRNAs in BOS and lung conditions in general, these results strongly suggest that circulating miRNAs could be used as potential biomarkers for BOS development.
AB - Lung transplantation (LTx) is the last treatment for patients suffering from end-stage lung diseases. Survival post-LTx is hampered by the development of the bronchiolitis obliterans syndrome (BOS) and diagnosis is often late. Given the urgent clinical need to recognize BOS patients at an early stage, we analyzed circulating miRNAs to identify possible stratification markers for BOS development post-transplantation. Therefore, pro-fibrotic (miR-21, miR-155), anti-fibrotic (miR-29a) and fibrosis-unrelated (miR-103, miR-191) miRNAs were analyzed in serum of end-stage lung disease patients and during LTx follow-up. Significant elevated levels of serum miRNAs were observed for all investigated miRNAs in both chronic obstructive pulmonary disease and interstitial lung disease patients compared to healthy controls. The same miRNAs were also significantly increased in the serum of BOS+ vs. BOS- patients. Most importantly, miR-21, miR-29a, miR-103, and miR-191 levels were significantly higher in BOS+ patients prior to clinical BOS diagnosis. We demonstrated that a selected group of miRNAs investigated is elevated in end-stage lung disease and BOS+ patients, prior to clinical BOS diagnosis. Even if further research is expedient on the prognostic value of circulating miRNAs in BOS and lung conditions in general, these results strongly suggest that circulating miRNAs could be used as potential biomarkers for BOS development.
KW - Biomarker
KW - Bronchiolitis obliterans syndrome
KW - Chronic lung allograft dysfunction
KW - Lung transplantation
KW - Micro-RNAs
UR - http://www.scopus.com/inward/record.url?scp=85018980686&partnerID=8YFLogxK
U2 - 10.1016/j.trim.2017.04.002
DO - 10.1016/j.trim.2017.04.002
M3 - Article
C2 - 28457921
SN - 0966-3274
VL - 42
SP - 1
EP - 4
JO - Transplant immunology
JF - Transplant immunology
ER -