Yajima Misako, Shiraki Atsuko, Daikoku Tohru, Oyama Yukari, Yoshida Yoshihiro, Shiraki Kimiyasu
Department of Virology, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Department of Virology, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
J Infect Chemother. 2015 Jun;21(6):427-33. doi: 10.1016/j.jiac.2015.01.012. Epub 2015 Feb 19.
Intravenous immunoglobulin (IVIG) is used to treat severe viral infection, especially varicella-zoster virus (VZV) and cytomegalovirus (CMV) infections. The neutralization antibody titers of eleven IVIG preparations from four companies were examined using VZV and CMV with and without complement. The neutralizing antibody titers of intact IgG preparations were three to six times higher after addition of complement. The effectiveness of the sulfonated IgG preparation was not enhanced by complement, but desulfonated IgG regained enhanced neutralization activity with complement. Antibody-dependent cellular cytotoxicity (ADCC) toward VZV-infected cells was observed with both intact and sulfonated IVIG and guinea pig splenocytes, but ADCC toward CMV-infected cells was not, although NK cell activity toward cells infected with VZV or CMV was detected by splenocytes. Sulfonated IVIG had no complement-activated neutralization of VZV and CMV but retained ADCC toward VZV with less activity after dilution than with intact IVIG. Because sulfonated IVIG is converted to the intact form after intravenous administration, it would show complement-enhanced neutralization and ADCC activity similar to that of intact IVIG in vivo. In this study we showed the effects of intact and sulfonated IgG on the functional activity of IgG against VZV and CMV.
静脉注射免疫球蛋白(IVIG)用于治疗严重的病毒感染,尤其是水痘带状疱疹病毒(VZV)和巨细胞病毒(CMV)感染。使用VZV和CMV在有补体和无补体的情况下检测了来自四家公司的11种IVIG制剂的中和抗体滴度。完整IgG制剂在添加补体后的中和抗体滴度高出三到六倍。磺化IgG制剂的有效性不会因补体而增强,但脱磺化IgG在补体存在下恢复了增强的中和活性。完整和磺化的IVIG以及豚鼠脾细胞均观察到对VZV感染细胞的抗体依赖性细胞毒性(ADCC),但对CMV感染细胞则未观察到ADCC,尽管脾细胞检测到对VZV或CMV感染细胞的NK细胞活性。磺化IVIG对VZV和CMV没有补体激活的中和作用,但保留了对VZV的ADCC,稀释后的活性低于完整IVIG。由于磺化IVIG在静脉给药后会转化为完整形式,因此它在体内会表现出与完整IVIG相似的补体增强中和作用和ADCC活性。在本研究中,我们展示了完整和磺化IgG对IgG针对VZV和CMV的功能活性的影响。