Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia
Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia
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DOI：
10.1182/blood-2008-09-181073
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发表时间：
2009-04-23
期刊：
影响因子：
20.3
通讯作者：
Karpatkin, Simon
中科院分区：
文献类型：
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作者：
Zhang, Wei;Nardi, Michael A.;Karpatkin, Simon
HIV-1免疫相关性血小板减少症（HIV-1- itp）患者具有一种独特的抗血小板抗体GPIIIa49-66，能够在补体缺失的情况下诱导血小板氧化分裂。HIV-1血清阳性药物滥用者比非药物滥用者更容易发生免疫性血小板减少症，同时感染丙型肝炎病毒（HCV）的比例高于非药物滥用者（90% vs 30%）。通过筛选以抗gpiia49 -66抗体为诱饵的噬菌体肽文库，寻找与HCV具有同源序列的肽。多个噬菌体肽克隆与HCV蛋白同源性达70%。HCV和HIV-ITP双重感染的血小板减少患者的血清与来自HCV核心包膜的4种非保守肽发生强烈反应。反应性与血小板计数呈负相关（r(2) = 0.7, P < 0.01）。在GPIIIa（-/-）小鼠中表达抗肽PHC09抗体，诱导野生型小鼠血小板减少。亲和纯化IgG抗PHC09诱导的体外氧化血小板破碎。双重感染HCV和HIV-1的药物滥用者血小板减少的发生率和严重程度更高，抗gpiiia49 -66/PHC09抗体滴度也更高。注射重组核包膜1的NZB/W F1小鼠产生抗PHC09抗体，血小板计数显著降低（P < 0.001）。因此，HCV核心包膜1可以通过GPIIIa49-66分子模拟诱导血小板减少。（血液杂志，2009;113:4086-4093）
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. (Blood. 2009; 113: 4086-4093)