DETECTION AND CHARACTERIZATION OF HCV RNA SEQUENCES IN IMMUNE GLOBULINS

1994年2月，巴克斯特医疗保健公司(BHC)宣布 所有免疫球蛋白静脉注射(IGIV)，Gammagard，Lot 因为有关于丙型肝炎传播的报道。全球范围内，大约 自1993年10月以来，报告了200起疑似传播病例。我们 对42个Gammagard批次进行了丙型肝炎病毒RNA检测，并对结果进行了评估 在起始血浆上进行的抗-HCV筛查的类型和 六六六中心收到的个案报告数目。还检测了丙型肝炎病毒核糖核酸 在疾控中心善意提供的一些美国接受者的血清中 (疾病控制和预防中心)。准备好的Gammagard抽签 在1988年至1993年11月期间，用逆转法测定了丙型肝炎病毒RNA 转录-聚合酶链式反应(RT-PCR)。手术过程是 在两个独立的实验室使用类似的嵌套引物进行检测 来自丙型肝炎病毒基因组的5‘非编码区。在Gammagard地块中 在1992年之前和在1992年由未经筛选的等离子体生产的 抗-丙型肝炎病毒，实验室A(血液科)检测到1例丙型肝炎病毒RNA 13批，而实验室B(输血科 疾病)在检测的9个批次中发现3批阳性。两个实验室都没有 检测5批血浆主要或部分产生的丙型肝炎病毒RNA 经EIA-1筛选(抗C100-3试验)。相比之下，在24件拍品中， 主要来自经EIA-2(多抗原试验)筛选的血浆，并由 两个实验室中，A实验室检测到16例丙型肝炎病毒RNA，14例检测到 化验所B检验的24批样本中，共有20批呈阳性反应。 一个或两个实验室提供的丙型肝炎病毒核糖核酸。这一结果意义重大。 (P&lt；0.0001)与通过生产的测试批次获得的结果相比 从未筛选或EIA-1筛选的血浆(3例中检测到丙型肝炎病毒RNA 由至少一个实验室提供的18个批次)。Gammagard拍卖行发现有 仅通过限制稀释产生最高水平的丙型肝炎病毒核糖核酸 来自EIA-2筛选的血浆，与大多数 变速箱。许多接收者，他们经常接受多个RT-PCR 许多阳性的Gammagard，被发现在他们的血清中有丙型肝炎病毒RNA。 因此，EIA-2对血浆的筛选似乎影响了这种存在 在Gammagard中发现了丙型肝炎病毒RNA。这样的筛选可能已经消除了络合作用 和/或中和抗体，产生不良结果。

In February 1994, Baxter Healthcare Corporation (BHC) announced the withdrawal of all Immune Globulin Intravenous (IGIV), Gammagard, lots because of reports of hepatitis C transmission. Worldwide, approximately 200 suspected transmissions have been reported since October 1993. We tested 42 Gammagard lots for HCV RNA and assessed the results in relation to the type of anti-HCV screening performed on the starting plasma and the number of case reports received by BHC. HCV RNA was also determined in some US recipients' sera which were kindly provided by the CDC (Centers for Disease Control and Prevention). Gammagard lots prepared between 1988 and November 1993 were assayed for HCV RNA by the reverse transcription-polymerase chain reaction (RT-PCR). The procedure was performed in two independent laboratories with similar nested primers from the 5'-noncoding region of the HCV genome. Of the Gammagard lots produced before and in 1992 from plasma that had not been screened for anti-HCV, laboratory A (Division of Hematology) detected HCV RNA in 1 of 13 lots, whereas laboratory B (Division of Transfusion Transmitted Diseases) found 3 lots positive among 9 tested. Neither laboratory detected HCV RNA in 5 lots produced from plasma mostly or partially screened by EIA-1 (anti-c100-3 test). In contrast, of 24 lots derived mostly from plasma screened by EIA-2 (multiantigen test) and tested by both laboratories, HCV RNA was detected in 16 by laboratory A and in 14 by laboratory B. A total of 20 of the 24 lots examined were positive for HCV RNA by one or both laboratories. This result is highly significant (p<0.0001) when compared to the results obtained by testing lots produced from either unscreened or EIA-1 screened plasma (HCV RNA detected in 3 of 18 lots by at least one laboratory). The Gammagard lot found to have the highest level of HCV RNA by limiting dilution was produced solely from EIA-2 screened plasma and was associated with the most transmissions. Many recipients, who often received multiple RT-PCR positive lots of Gammagard, were found to have HCV RNA in their sera. Thus, screening of plasma by EIA-2 appears to have effected the presence of HCV RNA in Gammagard. Such screening may have removed complexing and/or neutralizing antibodies with the resulting adverse outcome.