Autoimmunity to the p53 protein is a feature of systemic lupus erythematosus (SLE) related to anti-DNA antibodies

Johannes Herkel, Avishai Mimran, Neta Erez, Naaman Kam, Ansgar W. Lohse, Elisabeth Märker-Hermann, Varda Rotter, Irun R. Cohen

Research output: Contribution to journalArticlepeer-review

Abstract

The induction of anti-DNA autoantibodies in systemic lupus erythematosus (SLE) patients is problematic because mammalian DNA is poorly immunogenic at best. Here we demonstrate a chain of connected antibodies in SLE patient sera that could account for the induction of anti-DNA antibody, and possibly for some of the pathogenic features of SLE. We now report that SLE patients, in addition to anti-DNA, produce antibodies to the carboxy-terminal domain of the tumour suppressor molecule p53; this p53 domain recognizes damaged DNA. Hence, these anti-p53 antibodies could mimic damaged DNA immunologically. Indeed, SLE sera do contain anti-idiotypic antibodies to a prototypic anti-p53 antibody. Moreover, SLE anti-DNA antibodies also recognize this type of anti-p53 antibody. Indeed, binding of affinity-purified anti-DNA both to DNA and to the anti-p53 antibody could be blocked by a p53 peptide derived from the DNA-binding domain. This mimicry of the p53 DNA-binding domain by the SLE anti-DNA antibodies is functional: activation of the p53 molecule could be inhibited by such anti-DNA antibodies. Thus, anti-DNA antibodies may arise in SLE patients by a chain of idiotypic autoimmunity centered around p53 autoimmunity. The SLE anti-DNA and anti-p53 antibodies can functionally block p53 activation, and so could affect apoptosis.

Original languageEnglish
Pages (from-to)63-69
Number of pages7
JournalJournal of Autoimmunity
Volume17
Issue number1
DOIs
StatePublished - 1 Aug 2001
Externally publishedYes

Keywords

  • Anti-DNA
  • Apoptosis
  • Molecular mimicry
  • Systemic lupus erythematosus
  • p53

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