The appearance and disappearance of antiphospholipid autoantibodies subsequent to oxidation--reduction reactions

The mechanisms that cause the appearance of autoantibodies are not understood. Compared to normal antibody production, factors responsible for autoantibody synthesis are more complex; they are thought to disrupt the normal mechanisms proposed to eliminate or down-regulate self-antibodies or to interfere with anti-self-receptor editing. Data presented show that autoantibodies exist in the blood of all normal individuals. The autoantibodies appear after simple oxidation-reduction (redox) reactions and react by ELISA, immunofluorescence, flow cytometry, Western blots, and in lupus anticoagulant (LA) assays. Antiphospholipid antibody (aPL) specificities detected after redox are cardiolipin (aCL), antiphosphatidylserine (aPS), antiphosphatidylethanolamine (aPE), antiphosphatidylcholine (aPC), and LA. These antibody activities were confirmed in several outside laboratories. The aPL isotypes detected in ELISA are plasma protein-dependent and include IgG, IgA, and IgM. Oxidizing agents tested to date include hemin, KMnO4, and NaIO4. Furthermore, aPL appear after exposure to direct current (DC)-mediated electromotive force. Alternating current (AC) is ineffective. Commercial IvIg preparations, also a source of IgG autoantibodies, provide a less complex milieu than plasma or serum for studying the biology of aPL redox-mediated mechanisms. Inhibition of hemin-mediated IvIg aPL conversion can be achieved by the addition of antioxidants, e.g., ascorbic acid, hemopexin, apotransferrin, and by addition of normal plasma or serum. Remarkably, the aPL specificities in the blood of autoimmunity patients disappear subsequent to application of redox reactions. These data document the hitherto unknown existence of redox-reactive autoantibodies in all normal individuals. The evolutionary persistence of these redox-sensitive antibodies raises interesting possibilities about their potentially beneficial role in immunological homeostasis.