Biomarker signatures of sickle cell disease severity

• Published in: Blood cells, molecules, & diseases molecules, & diseases, 2018-09, Vol.72, p.1-9
• Main Authors: Du, Mengtian, Van Ness, Sarah, Gordeuk, Victor, Nouraie, Sayed M., Nekhai, Sergei, Gladwin, Mark, Steinberg, Martin H., Sebastiani, Paola
• Format: Article
• Language: English
• Subjects: Anemia, Sickle Cell - complications; Anemia, Sickle Cell - diagnosis; Biomarkers - analysis; Cluster Analysis; Clustering; Disease severity; Fetal hemoglobin; Hemolytic anemia; Humans; Molecular signature; Risk Assessment; Severity of Illness Index; Sickle cell disease; Vascular Diseases - diagnosis; Vascular Diseases - etiology
• ISSN: 1079-9796; 1096-0961
• DOI: 10.1016/j.bcmd.2018.05.001

Identifying sickle cell disease patients at high risk of complications could lead to personalized treatment and better prognosis but despite many advances prediction of the clinical course of these patients remains elusive. We propose a system-type approach to discover profiles of multiple, common biomarkers that correlate with morbidity and mortality in sickle cell disease. We used cluster analysis to discover 17 signatures of 17 common circulating biomarkers in 2320 participants of the Cooperative Study of Sickle Cell Disease, and evaluated the association of these signatures with risk for stroke, pain, leg ulceration, acute chest syndrome, avascular necrosis, seizure, death, and trend of fetal hemoglobin and hemolysis using longitudinally collected data. The analysis shows that some of the signatures are associated with reduced risk for complications, while others are associated with increased risk for complications. We also show that these signatures repeat in two more contemporary studies of sickle cell disease and correlate with recently discovered biomarkers of pulmonary vascular disease. With replication and further study, these biomarker signatures could become an important and affordable precision medicine tool to aid treatment and management of the disease. •Prediction of the clinical course of patients with sickle cell disease remains elusive.•We discovered signatures of 17 circulating biomarkers that correlate with morbidity and mortality in sickle cell disease.•We replicate the signatures in two studies and correlate with contemporary biomarkers of pulmonary vasculopathy.•The biomarker signatures could become an affordable precision medicine tool to aid treatment and management of the disease.