A peptide that shares similarity with bacterial antigens reverses thrombogenic properties of antiphospholipid antibodies in vivo

Silvia S. Pierangeli*, Miri Blank, Xiaowei Liu, Ricardo Espinola, Mati Fridkin, Mariano Vega Ostertag, Karen Roye-Green, E. Nigel Harris, Yehuda Shoenfeld

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: The factors causing production of antiphospholipid (aPL) antibodies remain unidentified. Recently, studies have shown that aPL and anti-β2Glycoprotein I (anti-β2GPI) antibodies with pathogenic properties can be generated with peptides from bacterial and viral origin, that mimic regions of β2GPI. These data suggest a molecular mimicry between bacterial/viral antigens and self-proteins. In this study we examined the ability of a synthetic peptide (named peptide A, NTLKTPRVGGC) that shares similarity with common bacterial antigens, to reverse aPL-mediated thrombosis in mice in vivo. Peptide A is also found in region I/II of β2GPI. A scrambled form of peptide A (named scA, GTKGCPNVRLT) was used as a control. Methods and Results: Sera from 29 patients with APS bound to peptide A but not to peptide scA by ELISA in a dose-dependent fashion. Cardiolipin (CL) liposomes inhibited the binding of IgG-APS by ELISA to peptide A by 35% and to CL by 56%. The inhibition of binding to cardiolipin and to peptide A was enhanced by addition of β2GPI to the liposomes. CL/peptide A liposomes but not peptide A alone inhibited the binding of IgG-APS to peptide A. β2GPI alone did not inhibit binding of IgG-APS to peptide A, to β2GPI or to CL. For the in vivo experiments, CD1 mice in groups of 20 were injected with affinity purified aPL antibodies or with control IgG-NHS twice intraperitoneally. Seventy hours after the first injection, and 30 min before the surgical procedure (induction of experimental thrombus) mice were infused i.v. in each group with either peptide A or with peptide scA. The femoral vein of the anesthetized mice were dissected to examine the dynamics of an induced thrombus in treated and control mice. The mean aCL titer of mice injected with aPL was 60 GPL units. Mice treated with aPL and infused with peptide scA produced significantly larger thrombi when compared to mice treated with IgG-NHS and peptide scA (2466±462 μm2vs 772.5±626.4 μm2). Treatment with peptide A significantly decreased thrombus size in mice injected with aPL antibodies (1063±890 μm2compared to 2466±462 μm2). Conclusion: The data indicates that a synthetic peptide that shares similarity with common bacterial antigens and with regions of β2GPI is capable to inhibit thrombogenic properties of aPL in mice. This may have important implications in designing new modalities of prevention and/or treatment of thrombosis in APS.

Original languageEnglish
Pages (from-to)217-225
Number of pages9
JournalJournal of Autoimmunity
Volume22
Issue number3
DOIs
StatePublished - May 2004

Funding

FundersFunder number
National Institutes of Health4706, S02GM08248
National Center for Research ResourcesG12RR003034
Ministry of Health, State of Israel

    Keywords

    • Anti-beta-2- glycoprotein-I
    • Antiphospholipid antibodies
    • Antiphospholipid syndrome
    • Bacteria
    • Peptides
    • Thrombosis
    • Viruses

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