Details

Autor(en) / Beteiligte

• Glassberg, Jeffrey
• Rahman, Adeeb H.
• Zafar, Mohammad
• Cromwell, Caroline
• Punzalan, Alexa
• Badimon, Juan Jose
• Aledort, Louis

Titel

Application of phospho-CyTOF to characterize immune activation in patients with sickle cell disease in an ex vivo model of thrombosis

Ist Teil von

• Journal of immunological methods, 2018-02, Vol.453, p.11-19

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Sickle cell disease (SCD) is a genetic disease caused by mutations in the beta globin gene, and inflammation plays a key role in driving many aspects of disease pathology. Early immune activation is believed to be associated with hemodynamic stresses and thrombus formation as cells traffic through blood vessels. We applied an extracorporeal perfusion system to model these effects ex vivo, and combined this with a phospho-CyTOF workflow to comprehensively evaluate single-cell signatures of early activation across all major circulating immune subsets. These approaches showed immune activation following passage through the perfusion chamber, most notably in monocytes, which exhibited platelet aggregation and significantly elevated expression of multiple phospho-proteins. Overall, these studies outline a robust and broadly applicable workflow to leverage phospho-CyTOF to characterize immune activation in response to ex vivo or in vivo perturbations and may facilitate identification of novel therapeutic targets in SCD and other inflammatory diseases. •Interactions between immune and hemostatic systems drive pathophysiology of SCD.•Phospho-CyTOF identified immune signatures in SCD after fluid shear thrombosis.•Platelet monocyte aggregates occur within minutes of ex-vivo thrombosis in SCD.