A new trick for an ancient drug: quinine dissociates antiphospholipid immune complexes

Quinine, a quinoline derivative, is an ancient antipyretic drug with antimalarial properties that has been phased out by more effective synthetic candidates. In previous studies we discovered that hydroxychloroquine (HCQ), a synthetic antimalarial with structural similarities to quinine, reduced the binding of antiphospholipid (aPL) immune complexes to phospholipid bilayers. We performed ellipsometry and atomic force microscopy (AFM) studies to measure the effect of quinine on dissociation of anti-β2-glycoprotein I (anti-β2GPI) immune complexes. We found that quinine desorbed pre-formed β2GPI-aPL immunoglobulin (Ig)G complexes from phospholipid bilayers at significantly lower molar concentrations than HCQ. Quinine also inhibited the formation of immune complexes with a higher efficacy than HCQ at equivalent drug concentrations of 0.2 mg/ml (0.192 ± 0.025 µg/cm2 for quinine vs. 0.352 ± 0.014 µg/cm2 for HCQ, p < 0.001). Furthermore, AFM imaging experiments revealed that addition of quinine disintegrated imm...