1. Specific cross-reaction of anti-dsDNA antibody with platelet integrin GPIIIa49-66
- Author
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Jianhui Wang, Suying Dang, Michael A. Nardi, Paolo Casali, Zongdong Li, Wei Zhang, and Hong Zan
- Subjects
Blood Platelets ,Models, Molecular ,Immunology ,Integrin ,Immunoblotting ,Molecular Sequence Data ,Enzyme-Linked Immunosorbent Assay ,Platelet Glycoprotein GPIIb-IIIa Complex ,Cross Reactions ,Epitope ,Article ,Epitopes ,Mice ,Random Allocation ,immune system diseases ,hemic and lymphatic diseases ,Immunology and Allergy ,Animals ,Humans ,Lupus Erythematosus, Systemic ,Amino Acid Sequence ,skin and connective tissue diseases ,Mice, Inbred BALB C ,Purpura, Thrombocytopenic, Idiopathic ,biology ,Platelet Count ,Anti-dsDNA antibodies ,Autoantibody ,DNA ,Molecular biology ,Complementarity Determining Regions ,Peptide Fragments ,Antibodies, Anti-Idiotypic ,Polyclonal antibodies ,Monoclonal ,biology.protein ,Female ,Antibody - 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.
- Published
- 2010