INHIBITION OF HISTONE ANTI-HISTONE REACTIVITY BY HISTONE-BINDING SERUM COMPONENTS - DIFFERENTIAL EFFECT ON ANTI-H1 VERSUS ANTI-H2B ANTIBODIES/

IgG fractions were purified on a protein G-agarose column from sera of both systemic lupus erythematosus (SLE) patients and healthy donors. All IgG fractions, after elution with 0-5 M acetic acid, reacted with histones in an anti-histone ELISA assay, and IgG anti-histone activity was in all instances higher in the IgG fraction than in the correspon ding whole serum. This was shown to be due to the presence in serum of histone-binding components that inhibited IgG binding to histones. Bo th normal human and SLE patients' sera had these histone-binding compo nents, and disparity between serum-positive and -negative anti-histone antibody (AHA) tests was not dependent on differences in the blocking capacity but on IgG antibody levels and avidity. Interaction of norma l serum IgG fraction with all five histones was of low avidity, wherea s interaction of IgG from AHA-positive SLE sera with both H1 and H2B h ad high avidity. Low-affinity antibodies to every histone fraction, bu t also high-affinity anti-H1 antibodies, were preferentially inhibited . Our data indicate that several serum protein components are inhibiti ng histone/anti-histone interaction and may play a protective role aga inst both high-affinity anti-H1 antibodies present in SLE patients, an d natural, low-affinity, anti-histone antibodies. As some acute phase proteins, notably C-reactive protein, bind to histones, it is conceiva ble that they play such a role. High-affinity anti-H2B antibodies, pre sent in some SLE patients, and not inhibited by these serum components , may, on the other hand, participate in the pathogenesis of the disea se.