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Blood, 15 July 2005, Vol. 106, No. 2, pp. 572-576. Prepublished online as a Blood First Edition Paper on March 17, 2005; DOI 10.1182/blood-2005-01-0243. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-01-0243v1 106/2/572    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Li, Z. Articles by Karpatkin, S. Search for Related Content PubMed PubMed Citation Articles by Li, Z. Articles by Karpatkin, S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Role of molecular mimicry to HIV-1 peptides in HIV-1–related immunologic thrombocytopenia Zongdong Li, Michael A. Nardi, and Simon Karpatkin From the New York University School of Medicine, New York, NY Patients with early HIV-1 infection develop an autoimmune thrombocytopenia in which antibody is directed against an immunodominant epitope of the 3 (glycoprotein IIIa [GPIIIa]) integrin, GPIIIa49-66. This antibody induces thrombocytopenia by a novel complement-independent mechanism in which platelets are fragmented by antibody-induced generation of H2O2 derived from the interaction of platelet nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and 12-lipoxygenase. To examine whether sharing of epitope between host and parasite may be responsible for this immunodominant epitope, we screened for antibody-reactive peptides capable of inhibiting platelet lysis and oxidation in vitro, using a filamentous phage display 7-mer peptide library. Fourteen of these phage-peptide clones were identified. Five shared close sequence similarity with GPIIIa49-66, as expected. Ten were molecular mimics with close sequence similarity to HIV-1 proteins nef, gag, env, and pol. Seven were synthesized as 10-mers from their known HIV-1 sequence and found to inhibit anti–GPIIIa49-66–induced platelet oxidation/fragmentation in vitro. Three rabbit antibodies raised against these peptides induced platelet oxidation/fragmentation in vitro and thrombocytopenia in vivo when passively transferred into mice. One of the peptides shared a known epitope region with HIV-1 protein nef and was derived from a variant region of the protein. These data provide strong support for molecular mimicry in HIV-1-immunologic thrombocytopenia within polymorphic regions of HIV-1 proteins. A known epitope of nef is particularly incriminated. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. Li, M. A. Nardi, J. Wu, R. Pan, W. Zhang, and S. Karpatkin Platelet Fragmentation Requires a Specific Structural Conformation of Human Monoclonal Antibody against {beta}3 Integrin J. Biol. Chem., February 8, 2008; 283(6): 3224 - 3230. [Abstract] [Full Text] [PDF] J. W. Semple, R. Aslam, M. Kim, E. R. Speck, and J. Freedman Platelet-bound lipopolysaccharide enhances Fc receptor mediated phagocytosis of IgG-opsonized platelets Blood, June 1, 2007; 109(11): 4803 - 4805. [Abstract] [Full Text] [PDF] J. C. Marecki, C. D. Cool, J. E. Parr, V. E. Beckey, P. A. Luciw, A. F. Tarantal, A. Carville, R. P. Shannon, A. Cota-Gomez, R. M. Tuder, et al. HIV-1 Nef Is Associated with Complex Pulmonary Vascular Lesions in SHIV-nef-infected Macaques Am. J. Respir. Crit. Care Med., August 15, 2006; 174(4): 437 - 445. [Abstract] [Full Text] [PDF]

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