title: Association of circulating transcriptomic profiles with mortality in sickle cell disease.
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.
authors.affiliation: Department of Medicine and Arizona Health Sciences Center, University of Arizona, Tucson, AZ.
authors.forename: Ankit A
authors.initials: AA
authors.lastname: Desai
authors.affiliation: Center for Research Informatics, Research Resources Center and Center for Clinical and Translational Science, University of Illinois at Chicago, Chicago, IL.
authors.forename: Zhengdeng
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Center for Research Informatics, Research Resources Center and Center for Clinical and Translational Science, University of Illinois at Chicago, Chicago, IL.
authors.forename: Neil
authors.initials: N
authors.lastname: Bahroos
authors.affiliation: Center for Research Informatics, Research Resources Center and Center for Clinical and Translational Science, University of Illinois at Chicago, Chicago, IL.
authors.forename: Mark
authors.initials: M
authors.lastname: Maienschein-Cline
authors.affiliation: Department of Medicine, University of Illinois Hospitals and Health Sciences System, Chicago, IL.
authors.forename: Santosh L
authors.initials: SL
authors.lastname: Saraf
authors.affiliation: Department of Medicine, University of Illinois Hospitals and Health Sciences System, Chicago, IL.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medicine, University of Illinois Hospitals and Health Sciences System, Chicago, IL.
authors.forename: Binal N
authors.initials: BN
authors.lastname: Shah
authors.affiliation: Department of Medicine, Howard University, Washington, DC; and.
authors.forename: Seyed M
authors.initials: SM
authors.lastname: Nouraie
authors.affiliation: Department of Medicine, University of Illinois Hospitals and Health Sciences System, Chicago, IL.
authors.forename: Taimur
authors.initials: T
authors.lastname: Abbasi
authors.affiliation: Department of Medicine, University of Chicago Medical Center, Chicago, IL.
authors.forename: Amit R
authors.initials: AR
authors.lastname: Patel
authors.affiliation: Department of Medicine, University of Chicago Medical Center, Chicago, IL.
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Lang
authors.affiliation: Department of Medicine and Arizona Health Sciences Center, University of Arizona, Tucson, AZ.
authors.forename: Yves
authors.initials: Y
authors.lastname: Lussier
authors.affiliation: Department of Medicine and Arizona Health Sciences Center, University of Arizona, Tucson, AZ.
authors.forename: Joe G N
authors.initials: JGN
authors.lastname: Garcia
authors.affiliation: Department of Medicine, University of Illinois Hospitals and Health Sciences System, Chicago, IL.
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
authors.affiliation: Department of Medicine, University of Illinois Hospitals and Health Sciences System, Chicago, IL.
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Machado
mesh_terms: D056586:Acute Chest Syndrome / Q000235:genetics; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics* / Q000401:mortality; D002648:Child; D015331:Cohort Studies; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D059467:Transcriptome; D014262:Tricuspid Valve Insufficiency / Q000235:genetics; D055815:Young Adult
chemical_list: D006454:Hemoglobins