Interaction of the antiphospholipid syndrome autoantigen beta-2 glycoprotein I with DNA and neutrophil extracellular traps

Abstract

Beta-2 glycoprotein I (β₂GPI) is a phospholipid-binding plasma protein and prominent autoantigen in antiphospholipid syndrome (APS). Here, we tested the hypothesis that β₂GPI might bind to not only phospholipids, but also cell-free DNA and neutrophil extracellular traps (NETs). We report that β₂GPI interacts with cell-free DNA from different species, as well as NETs, in a dose-dependent manner, retarding their migration in an agarose-gel electrophoretic mobility shift assay. We confirm the direct binding interaction of β₂GPI with DNA and NETs by ELISA. We also demonstrate that β₂GPI colocalizes with NET strands by immunofluorescence microscopy. Finally, we provide evidence that β₂GPI-DNA complexes can be detected in the plasma of APS patients, where they positively correlate with an established biomarker of NET remnants. Taken together, our findings indicate that β₂GPI interacts with DNA and NETs, and suggest that this interaction may play a role as a perpetuator and/or instigator of autoimmunity in APS.

Keywords: Antiphospholipid antibodies; Antiphospholipid syndrome; DNA; Lupus; Neutrophil extracellular traps; beta-2 glycoprotein I.