Boo Irene, Fischer Alexandra E, Johnson Doug, Chin Ruth, Giourouki Maxine, Bharadwaj Mandvi, Bowden Scott, Torresi Joseph, Drummer Heidi
Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Prahran, Victoria 3001, Australia.
J Clin Virol. 2007 Aug;39(4):288-94. doi: 10.1016/j.jcv.2007.04.019. Epub 2007 Jun 14.
The role of neutralizing antibody (NAb) in determining response to antiviral therapy has not been established.
In this study we have analysed the kinetic's of the NAb response in patients with chronic hepatitis C who received antiviral therapy.
Seventeen patients infected with genotype 1, 2a/c or 3a hepatitis C virus (HCV) were enrolled, eight with a sustained virological response (SVR), five non-responders and four relapsers.
The mean NAb titre required to neutralize 50% of the E1E2-pp in patients who achieved an SVR (294+/-S.D. 51), in relapsers (246+/-S.D. 61.7) and non-responders (286+/-S.D. 80.95) did not differ significantly between the patient groups and did not alter during the course of treatment (P>0.01). Genetic variation present before antiviral therapy was analysed by single strand conformation polymorphism (SSCP) and failed to demonstrate a significant difference in the mean number of amplified E1E2 DNA fragments from the serum of patients who achieved an SVR (3.15+/-S.D. 1.53), relapsers (2.8+/-S.D. 1.32) or non-responders (3.69+/-S.D. 1.75). The baseline serum HCV viral loads were also not significantly different between patients who achieved an SVR (1.4 x 10(6) copies/ml; +/-S.D. 2.4 x 10(6)), relapsers (1.3 x 10(7) copies/ml; +/-S.D. 2.4 x 10(7)) and non-responders (1.5 x 10(6) copies/ml; +/-S.D. 1.1 x 10(6)).
We have shown that neutralizing anti-HCVpp antibody is not associated with response to antiviral therapy. In addition, there was no correlation between baseline virological load, circulating viral quasi-species, NAb titres and final response to treatment.
中和抗体(NAb)在确定抗病毒治疗反应中的作用尚未明确。
在本研究中,我们分析了接受抗病毒治疗的慢性丙型肝炎患者中NAb反应的动力学。
纳入了17例感染1、2a/c或3a基因型丙型肝炎病毒(HCV)的患者,其中8例获得持续病毒学应答(SVR),5例无应答者,4例复发者。
实现SVR的患者(294±标准差51)、复发者(246±标准差61.7)和无应答者(286±标准差80.95)中中和50%的E1E2-pp所需的平均NAb滴度在各患者组之间无显著差异,且在治疗过程中未发生改变(P>0.01)。通过单链构象多态性(SSCP)分析抗病毒治疗前存在的基因变异,未显示出实现SVR的患者(3.15±标准差1.53)、复发者(2.8±标准差1.32)或无应答者(3.69±标准差1.75)血清中扩增的E1E2 DNA片段平均数量有显著差异。实现SVR的患者(1.4×10⁶拷贝/ml;±标准差2.4×10⁶)、复发者(1.3×10⁷拷贝/ml;±标准差2.4×10⁷)和无应答者(1.5×10⁶拷贝/ml;±标准差1.1×10⁶)的基线血清HCV病毒载量也无显著差异。
我们已表明,中和抗-HCVpp抗体与抗病毒治疗反应无关。此外,基线病毒学载量、循环病毒准种、NAb滴度与最终治疗反应之间无相关性。