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 corresponding whole serum. This was shown to be due to the presence in serum of histone-binding components that inhibited IgG binding to histones. Both normal human and SLE patients' sera had these histone-binding components, 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 normal serum IgG fraction with all five histones was of low avidity, whereas interaction of IgG from AHA-positive SLE sera with both H1 and H2B had high avidity. Low-affinity antibodies to every histone fraction, but also high-affinity anti-H1 antibodies, were preferentially inhibited. Our data indicate that several serum protein components are inhibiting histone/anti-histone interaction and may play a protective role against both high-affinity anti-H1 antibodies present in SLE patients, and natural, low-affinity, anti-histone antibodies. As some acute phase proteins, notably C-reactive protein, bind to histones, it is conceivable that they play such a role. High-affinity anti-H2B antibodies, present in some SLE patients, and not inhibited by these serum components, may, on the other hand, participate in the pathogenesis of the disease.
Bustos
A
A
Department of Immunology, Hospital Universitario San Carlos, Madrid, Spain.
Boimorto
R
R
Subiza
J L
JL
Pereira
L F
LF
Marco
M
M
Figueredo
M A
MA
de la Concha
E G
EG
D000915:Antibody Affinity; D001323:Autoantibodies / Q000097:blood*; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000097:blood*; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000302:isolation & purification; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*
D001323:Autoantibodies; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D007074:Immunoglobulin G