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

Beta-2 glycoprotein I (β ₂ GPI) is a phospholipid-binding plasma protein and prominent autoantigen in antiphospholipid syndrome (APS). Here, we tested the hypothesis that β ₂ GPI might bind to not only phospholipids, but also cell-free DNA and neutrophil extracellular traps (NETs). We report that β ₂ GPI 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 β ₂ GPI with DNA and NETs by ELISA. We also demonstrate that β ₂ GPI colocalizes with NET strands by immunofluorescence microscopy. Finally, we provide evidence that β ₂ GPI-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 β ₂ GPI interacts with DNA and NETs, and suggest that this interaction may play a role as a perpetuator and/or instigator of autoimmunity in APS.
Competing Interests: Declaration of Competing Interest None of the authors has any financial conflict of interest to disclose.
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