Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia.

Abstract

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.

• Authors: Wei Zhang, Michael A Nardi, William Borkowsky, Zongdong Li, Simon Karpatkin
• Journal: Blood (Blood) Vol. 113 Issue 17 Pg. 4086-93 (Apr 23 2009) ISSN: 1528-0020 [Electronic] United States
• PMID: 19023115 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• Integrin beta3
• Peptide Library
• Viral Envelope Proteins

Topics

• Animals
• Antibodies, Viral (immunology)
• Blood Platelets (metabolism)
• Cell Count
• Cross Reactions (immunology)
• Female
• Hepacivirus
• Hepatitis C (complications, genetics, immunology, metabolism)
• Integrin beta3 (genetics, metabolism)
• Mice
• Mice, Knockout
• Molecular Mimicry
• Oxidative Stress
• Peptide Library
• Thrombocytopenia (etiology, genetics, immunology, metabolism)
• Viral Envelope Proteins (immunology, metabolism)