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Blood, 23 April 2009, Vol. 113, No. 17, pp. 4086-4093.
Prepublished online as a Blood First Edition Paper on November 20, 2008; DOI 10.1182/blood-2008-09-181073.


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Submitted September 25, 2008
Accepted November 12, 2008

Role of molecular mimickry of hepatitis C-virus (HCV) protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia

Wei Zhang, Michael A Nardi, Zongdong Li, William Borkowsky, and Simon Karpatkin*

Department of Medicine, New York University School of Medicine, New York, NY, United States
Department of Pediatrics, New York University School of Medicine, New York, NY, United States

* Corresponding author; email: simon.karpatkin{at}med.nyu.edu.

HIV-1-ITP patients have a unique Ab against platelet GPIIIa49-66 capable of inducing oxidative platelet fragmentation in the absence of complement. HIV-1-seropositive drug abusers are more prone to develop immune thrombocytopenia (HIV-1-ITP) than non-drug abusers and have a higher coinfection with Hepatitis C virus than non-drug abusers (90% vs 30%). Molecular mimickry with a Hepatitis C protein was sought by screening a phage peptide library with anti-GPIIIa49-66 antibody as bait for peptides sharing homology sequences with HCV protein. Several phage peptide clones had 70% homology with HCV protein. Sera from dually infected thrombocytopenic patients with HCV and HIV-ITP reacted strongly with 4 non-conserved peptides from HCV core-envelope 1. Reactivity correlated inversely with platelet count, r2=0.7, p<0.01. Ab raised against peptide PHC09 in GPIIIa-/- mice induced severe thrombocytopenia in wild-type mice. Affinity-purified IgG against PHC09 induced oxidative platelet fragmentation in vitro. Drug abusers dually infected with HCV and HIV-1 had a greater incidence and severity of thrombocytopenia as well as greater incidence and titer of anti-GPIIIa49-66/PHC09 Ab. NZB/W F1 mice injected with recombinant core envelope 1 developed Ab vs PHC09 and significantly decreased their platelet count, p<0.001. Thus, HCV core envelope 1 can induce thrombocytopenia by molecular mimicry with GPIIIa49-66.


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