Association of circulating transcriptomic profiles with mortality in sickle cell disease

作者：Desai Ankit A; Lei Zhengdeng; Bahroos Neil; Maienschein Cline Mark; Saraf Santosh L; Zhang Xu; Shah Binal N; Nouraie Seyed M; Abbasi Taimur; Patel Amit R; Lang Roberto M; Lussier Yves; Garcia Joe G N; Gordeuk Victor R; Machado Roberto F

来源：Blood, 2017, 129(22): 3009-3016.

DOI：10.1182/blood-2016-11-752279

Sickle cell disease (SCD) complications are associated with increased morbidity and risk of mortality. We sought to identify a circulating transcriptomic profile predictive of these poor outcomes in SCD. Training and testing cohorts consisting of adult patients with SCD were recruited and prospectively followed. A pathway-based signature derived from grouping peripheral blood mononuclear cell transcriptomes distinguished 2 patient clusters with differences in survival in the training cohort. These findings were validated in a testing cohort in which the association between cluster 1 molecular profiling and mortality remained significant in a fully adjusted model. In a third cohort of West African children with SCD, cluster 1 differentiated SCD severity using a published scoring index. Finally, a risk score composed of assigning weights to cluster 1 profiling, along with established clinical risk factors using tricuspid regurgitation velocity, white blood cell count, history of acute chest syndrome, and hemoglobin levels, demonstrated a higher hazard ratio for mortality in both the training and testing cohorts compared with clinical risk factors or cluster 1 data alone. Circulating transcriptomic profiles are a powerful method to risk-stratify severity of disease and poor outcomes in both children and adults, respectively, with SCD and highlight potential associated molecular pathways.

• 出版日期2017-6-1