HISTONES INTERACT WITH ANIONIC PHOSPHOLIPIDS WITH HIGH AVIDITY - ITS RELEVANCE FOR THE BINDING OF HISTONE-ANTIHISTONE IMMUNE-COMPLEXES

Antibodies recognizing anionic phospholipids have been described in sy stemic lupus erythematosus (SLE) and other autoimmune diseases. Recent studies have shown that some of these antibodies may recognize a card iolipin-binding protein (apolipoprotein H) rather than phospholipids. A similar possibility is conceivable for other cardiolipin-binding pro teins that are targets of autoantibodies. In this study we have addres sed whether this might be the case for histones, a set of highly catio nic and widely distributed proteins that react in a well known autoant ibody system. Our results indicate that: (i) histones bind to anionic phospholipids (cardiolipin and phosphatidylserine) with high avidity, but not to zwitterionic phospholipids (phosphatidylcholine); (ii) mono clonal and polyclonal antihistone antibodies recognize histones bound to cardiolipin; (iii) the addition of histones to serum samples contai ning antihistone antibodies often enhances their anticardiolipin react ivity. In addition, we have found that antihistone-producing hybridoma s derived from MRL-lpr mice may show anticardiolipin activity due to t he presence of histones in the cell culture supernatants with the resu ltant formation of immune complexes. Taken together, the results sugge st a potential role for histones in the anticardiolipin activity detec ted in sera containing antihistone antibodies. These histone-phospholi pid interactions should be taken into account when evaluating the path ogenic effects of antihistone antibodies or other autoantibodies react ing with nuclear components (e.g. nucleosomes) containing histones.