The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus - PubMed (original) (raw)

The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus

R W Burlingame et al. J Clin Invest. 1994 Jul.

Abstract

To gain insight into the mechanisms of autoantibody induction, sera from 40 patients with systemic lupus erythematosus (SLE) were tested by ELISAs for antibody binding to denatured individual histones, native histone-histone complexes, histone-DNA subnucleosome complexes, three forms of chromatin, and DNA. Whole chromatin was the most reactive substrate, with 88% of the patients positive. By chi-square analysis, only the presence of anti-(H2A-H2B), anti-[(H2A-H2B)-DNA], and antichromatin were correlated with kidney disease measured by proteinuria > 0.5 g/d. SLE patients could be divided into two groups based on their antibody-binding pattern to the above substrates. Antibodies from about half of the patients reacted with chromatin and the (H2A-H2B)-DNA subnucleosome complex but displayed very low or no reactivity with native DNA or the (H3-H4)2-DNA subnucleosome complex. An additional third of the patients had antibody reactivity to chromatin, as well as to both subnucleosome structures and DNA. Strikingly, all sera that bound to any of the components of chromatin also bound to whole chromatin, and adsorption with chromatin removed 85-100% of reactivity to (H2A-H2B)-DNA, (H3-H4)2-DNA, and native DNA. Individual sera often bound to several different epitopes on chromatin, with some epitopes requiring quaternary protein-DNA interactions. These results are consistent with chromatin being a potent immunogenic stimulus in SLE. Taken together with previous studies, we suggest that antibody activity to the (H2A-H2B)-DNA component signals the initial breakdown of immune tolerance whereas responses to (H3-H4)2-DNA and native DNA reflect subsequent global loss of tolerance to chromatin.

PubMed Disclaimer

Similar articles

Cited by

References

    1. J Exp Med. 1989 Jun 1;169(6):1879-94 - PubMed
    1. Biochemistry. 1982 Aug 31;21(18):4362-70 - PubMed
    1. N Engl J Med. 1988 Jun 2;318(22):1431-6 - PubMed
    1. FEBS Lett. 1971 May 20;14(5):333-337 - PubMed
    1. J Immunol. 1990 Oct 1;145(7):2322-32 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources