Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia.
Patients with HIV-1 immune-related thrombocytopenia (HIV-1-ITP) 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 than non-drug abusers and have a higher coinfection with hepatitis C virus (HCV) than non-drug abusers (90% vs 30%). Molecular mimicry was sought by screening a phage peptide library with anti-GPIIIa49-66 antibody as bait for peptides sharing homology sequences with HCV. 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 nonconserved peptides from HCV core envelope 1. Reactivity correlated inversely with platelet count (r(2) = 0.7, P < .01). Ab raised against peptide PHC09 in GPIIIa(-/-) mice induced 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 titer of anti-GPIIIa49-66/PHC09 Ab. NZB/W F1 mice injected with recombinant core envelope 1 developed Ab versus PHC09 and significantly decreased their platelet count (P < .001). Thus, HCV core envelope 1 can induce thrombocytopenia by molecular mimicry with GPIIIa49-66.
Zhang
Wei
W
Department of Medicine, New York University School of Medicine, NY 10016, USA.
Nardi
Michael A
MA
Borkowsky
William
W
Li
Zongdong
Z
Karpatkin
Simon
S
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001792:Blood Platelets / Q000378:metabolism; D002452:Cell Count; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018716:Molecular Mimicry; D018384:Oxidative Stress; D019151:Peptide Library; D013921:Thrombocytopenia / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism*
D000914:Antibodies, Viral; D039661:Integrin beta3; D019151:Peptide Library; D014759:Viral Envelope Proteins