DETECTION AND CHARACTERIZATION OF HCV RNA SEQUENCES IN IMMUNE GLOBULINS

1994年2月，巴克斯特医疗保健公司撤回了所有 含Gammaguard的静脉注射免疫球蛋白（人）（IGIV）批次 （由商业血浆（源血浆和回收血浆）生产） 血浆）和Polygam（从美国红十字会回收的血浆），因为 有关可能传播丙型肝炎病毒的报告。 以来 然后，我们一直在与巴克斯特的IGIV和血清进行密集的工作， 一些收件人，并试图了解这种爆发的原因。 之前，我们在3个批次的Gammaguard中均未检出HCV RNA 和1988-89年生产的2批Polygam。 到目前为止，我们已经分析了 PCR法检测共40批Gammaguard。 31份复溶样品 还将批次提供给肝炎实验室（HL）进行PCR和 通过RIBA-2测定抗HCV反应性。 生产的Gammaguard批次 自1992年以来，发现抗-HCV阴性。 对于生产批次， 1993年，26批样品中15批检出HCVRNA，其中21批为阳性， 两个实验室检测，我们检测到12个阳性，而HL检测到13个 阳性（14个批次的PCR结果在2个实验室之间一致）。 为 在1988-1992年的14批中，仅在1批中检出HCVRNA; 两个实验室检测了10个批次，我们发现1个阳性，而HL发现相同 批和另外2批阳性。 我们所有的15个阳性批次和12个 HL的13个阳性批次中，有10个是自1993年4月以来生产的， 与巴克斯特生产100%衍生IGIV批次的时间一致 来自多抗原抗HCV筛选血浆。 同时检测到HCV RNA 18例受者血清中有16例有阳性反应。 因此，我们强烈怀疑， HCV的保护性抗体可能已经从IGIV中去除， 血浆多抗原筛查。 我们在4个gammaguard批次中找到1个 从回收的血浆制备的HCV RNA阳性，而HL发现 3批阳性。 然而，通过有限稀释，我们鉴定了8个批次 从具有更高水平HCV RNA的源血浆制备。我们在 表征2个相关批次中存在的HCV RNA的过程 我们确定那里的HCV RNA水平最高。

In February 1994, Baxter Healthcare Corporation, withdrew all of their Immune Globulin Intravenous (Human) (IGIV) lots which include Gammaguard (manufactured from commercial plasma, both Source Plasma and recovered plasma) and Polygam (recovered plasma from American Red cross) because of the reports of possible hepatitis C virus (HCV) transmission. Since then, we have been working intensively with Baxter's IGIV and sera from some recipients, and tried to understand the rationale for such outbreak. Previously we did not detect HCV RNA in any of the 3 lots of Gammaguard and 2 lots of Polygam made during 1988-89. Thus far, we have assayed a total of 40 lots of Gammaguard by PCR. Reconstituted samples from 31 lots were also given to Hepatitis Laboratory (HL) for PCR and for assaying anti-HCV reactivity by RIBA-2. Gammaguard lots manufactured since 1992 were found to be anti-HCV negative. For lots manufactured in 1993, we detected HCV RNA in 15 of 26 lots; among them, 21 lots were assayed by both labs, and we detected 12 positive while HL detected 13 positive (PCR results from 14 lots were agreeable between 2 labs). For lots made during 1988-1992, we found HCV RNA only in 1 of 14 lots; among 10 lots assayed by both labs, we found 1 positive while HL found the same lot and additonal 2 lots positive. All of our 15 positive lots and 12 of HL's 13 positive lots were manufactured since April 1993, which coincides with the time when Baxter manufactured IGIV lots 100% derived from multiantigen anti-HCV screened plasma. HCV RNA was also detected in 16 of 18 recipients'sera. Therefore, we strongly suspect that protective antibodies for HCV might have been removed from IGIV because of multiantigen screening of plasma. We found 1 of 4 gammaguard lots prepared from recovered plasma was positive for HCV RNA while HL found 3 lots positive. However, by limiting dilution we identified 8 lots prepared from Source Plasma having higher levels of HCV RNA. We are in the process of characterizing the HCV RNA present in 2 implicated lots which we determined to have the highest levels of HCV RNA among all.