Specific cross-reaction of anti-dsDNA antibody with platelet integrin GPIIIa49-66

Wei Zhang, Suying Dang, Jianhui Wang, Michael A. Nardi, Hong Zan, Paolo Casali, Zongdong Li

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Anti-platelet autoantibodies are frequently found in systemic lupus erythematosus (SLE) patients and contribute to the development of SLE-associated immunologic thrombocytopenia (SLE-ITP). Although the correlation of anti-dsDNA autoantibody with platelet-associated antibody has been reported, the potential mechanism underlying such a correlation is incompletely understood. We have reported that anti-platelet integrin GPIIIa49-66 (CAPESIEFPVSEARVLED) autoantibodies play a major role in the development of HIV-1-related thrombocytopenia (HIV-1-ITP). The strong negative charge of GPIIIa49-66 prompts us to investigate whether GPIIIa49-66 can be an epitope mimicking dsDNA. We report here that anti-GPIIIa49-66 antibodies are found in three out of nine SLE-ITP patients. Double-stranded (ds) DNA competitively inhibited the binding of purified patient anti-dsDNA antibodies to GPIIIa49-66 peptide. Both polyclonal and monoclonal anti-GPIIIa49-66 antibodies are able to cross-react with dsDNA. Consistent with previous reports, the DNA binding activities of anti-GPIIIa49-66 antibodies are mainly dependent on the positively charged amino acid in the heavy-chain complementarity-determining region 3 (HCDR3). The HCDR3 of human SLE anti-dsDNA monoclonal antibody (mAb) 412.67 demonstrates a similar positively charged amino acid chain orientation compared with that of anti-GPIIIa49-66 mAb A11, and it cross-reacts with GPIIIa49-66 peptide. Purified anti-GPIIIa49-66 antibodies from SLE-ITP patients are able to induce platelet fragmentation in vitro and to induce thrombocytopenia in vivo. Thus, our data suggest that specific epitope cross-reaction between GPIIIa49-66 and dsDNA could be a mechanism involved in the development of SLE-associated thrombocytopenia.

Original languageEnglish (US)
Pages (from-to)682-689
Number of pages8
JournalAutoimmunity
Volume43
Issue number8
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

Keywords

  • Autoantibody
  • anti-dsDNA autoantibody
  • platelet-associated antibody (PAIgG)
  • systemic lupus erythematosus (SLE)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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