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Association of circulating transcriptomic profiles with mortality in sickle cell disease
source: Blood
year: 2017
authors: Desai AA, Lei Z, Bahroos N, Maienschein-Cline M, Saraf SL, Zhang X, Shah BN, Nouraie SM, Abbasi T, Patel AR, Lang RM, Lussier Y, Garcia JGN, Gordeuk VR, Machado RF
summary/abstract: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
organization: University of Arizona; University of Illinois at Chicago; University of Illinois Hospitals and Health Sciences System; Howard University, Washington, DC; University of Chicago Medical CenterDOI: 10.1182/blood-2016-11-752279
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