Gene Expression Patterns That Predict Immune-Mediated Thrombosis
Abstract
Background: Antiphospholipid antibody syndrome (APS) is a complex, autoimmune thrombotic disorder with defined clinical phenotypes. Although not all patients with elevated antiphospholipid antibody (aPLA) levels develop clinical complications, the severity of these potential events mandates aggressive and extended, lifelong antithrombotic therapy.
Methods: A total group of 129 patients (57 patients with APS and venous thromboembolism [VTE], 32 patients with VTE without aPLA, 32 patients with aPLA only, and 7 normal healthy patients) were enrolled. RNA was prepared from peripheral mononuclear cells and used for DNA microarray analysis. Patterns of gene expression that characterize APS as well as thrombosis in the presence of aPLA were identified by hierarchical clustering and supervised analyses using binary regression methods.
Results: Gene expression profiles were developed that identify and predict individuals with APS, including the use of a distinct cohort for validation, from patients with VTE without aPLA. Importantly, similar methods identified expression profiles that accurately predicted those patients with aPLA at high risk for thrombotic events. Again, this was validated in a separate cohort of patients.
Conclusions: The ability to predict APS, but more importantly those patients at risk for thrombosis, opens the way to a more effective strategy for clinical management of these patients. This also represents a paradigm for a genomic approach that can be applied to other populations of patients with arterial and venous thrombosis; providing for more effective clinical management of disease while also reflecting the possible underlying biologic processes.
PLEASE NOTE: We realized that there was a duplication error in the data posted and are trying to resolve this discrepancy.
Authors
Anil Potti, Andrea Bild, Holly Dressman, Deborah Lewis, Joseph R. Nevins, Thomas L. Ortel
Contact
- Anil Potti (anil.potti@duke.edu)