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Rheumatology Advance Access originally published online on February 28, 2003
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Rheumatology 2003; 42: 453-463
© 2003 British Society for Rheumatology

Studies of human polyclonal and monoclonal antibodies binding to lupus autoantigens and cross-reactive antigens

A. Sharma, D. Isenberg and B. Diamond1

Centre for Rheumatology, University College London, London W1T 4NJ, UK and
1 Albert Einstein College of Medicine, New York, NY 1461, USA

Background. Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease serologically characterized by production of a variety of autoantibodies. Antibodies to double-stranded (ds) DNA are considered to be a diagnostic marker in SLE and their presence often correlates with active disease. The murine R4A anti-dsDNA antibody was found to cross-react with a peptide, D/EWD/EYS/G (R4A peptide), identified by analysing decapeptides selected from a peptide library. The R4A peptide inhibited binding of antibody to dsDNA and antibody deposition in kidneys in vivo. In other previous work, mice immunized with the peptide in a decapeptide form bound to a polylysine backbone, multiple antigenic peptide, were found to develop both anti-DNA and anticardiolipin antibodies.

Methods. To determine if human anti-DNA antibodies bind R4A peptide, we investigated the binding of monoclonal and polyclonal anti-dsDNA and anticardiolipin antibodies to the R4A peptide from patients with SLE.

Results. DNA binding by four immunoglobulin (Ig) G and two IgM human monoclonal anti-DNA antibodies was inhibited by the R4A peptide. While monomeric peptide was unable to inhibit affinity-purified polyclonal anti-DNA antibodies, serum anti-DNA reactivity was inhibited by an octameric form of the peptide in 10 SLE patients.

Conclusions. Human anti-DNA reactivity includes the same fine specificity as that present in murine anti-DNA reactivity. Peptide binding might be a useful surrogate marker for SLE.

Correspondence to: D. Isenberg, Centre for Rheumatology, University College London, 4th Floor, Arthur Stanley House, 40–50 Tottenham Street, London W1T 4NJ, UK. E-mail: d.isenberg{at}ucl.ac.uk


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