Molecular Biology Reports

, Volume 23, Issue 3–4, pp 159–166 | Cite as

Autoantibody to the nucleosome subunit (H2A-H2B)-DNA is an early and ubiquitous feature of lupus-like conditions

  • Rufus W. Burlingame
  • Robert L. Rubin
Autoantibodies as Clinical Markers

Abstract

Chromatin, a huge polymer of nucleosomes, has been implicated as an important target of autoantibodies in idiopathic and drug-induced lupus for decades, but the antigenicity of chromatin has only recently been dissected. IgG reactivity with the (H2A-H2B)-DNA complex, a subunit of the nucleosome, is present in the majority of patients with systemic lupus erythematosus, in >90% of patients with lupus induced by procainamide and in individual patients with lupus induced by a variety of other drugs, but is not seen in people taking these medications who are clinically asymptomatic. Anti-[(H2A-H2B)-DNA] accounted for the bulk of the anti-chromatin activity in drug-induced lupus. The earliest detectable autoantibody in lupus-prone mice recognized similar epitopes in the (H2A-H2B)-DNA subnucleosome complex; as the immune response progressed, native DNA and other constituents of chromatin became antigenic. The importance of chromatin-reactive T cells in the anti-[(H2A-H2B)-DNA] response is suggested by the presence of somatic mutations in antibody VH and VL regions, their perdominant IgG isotype and the similarity in kinetics of their production to that of conventional T cell dependent antigens. Together with the serologic data from human lupus-like disease, these results are consistent with chromatin being a common stimulant for both B and T cells. While chromatin-reactive antibodies are closely associated with systemic disease and have recently been implicated in glomerulonephritis in SLE, the absence of renal disease in drug-induced lupus indicates that additional abnormalities are required to manifest the serious pathogenic potential of anti-[(H2A-H2B)-DNA] antibodies.

Key words

anti-chromatin (nucleosome) antibodies drug-induced lupus systemic lupus erythematosus 

Abbreviations

APC

antigen present cells

DIL

drug-induced lupus

ELISA

enzyme-linked immunosorbent assay

GBM

glomerular basement membrane

[(H2A-H2B)-DNA]

an intermolecular complex consisting of DNA and a dimer of histones H2A and H2B

nDNA

native (double-stranded) DNA

SLE

systemic lupus erythematosus

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Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Rufus W. Burlingame
    • 1
  • Robert L. Rubin
    • 2
  1. 1.Scripps Reference LaboratorySan DiegoUSA
  2. 2.W.M. Keck Autoimmune Disease Center, Department of Molecular and Experimental MedicineThe Scripps Research InstituteLa JollaUSA

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