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

Beta-2 glycoprotein I (βGPI) is a phospholipid-binding plasma protein and prominent autoantigen in antiphospholipid syndrome (APS). Here, we tested the hypothesis that βGPI might bind to not only phospholipids, but also cell-free DNA and neutrophil extracellular traps (NETs). We report that βGPI 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 βGPI with DNA and NETs by ELISA. We also demonstrate that βGPI colocalizes with NET strands by immunofluorescence microscopy. Finally, we provide evidence that βGPI-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 βGPI interacts with DNA and NETs, and suggest that this interaction may play a role as a perpetuator and/or instigator of autoimmunity in APS.