Schiff R I
Vox Sang. 1985;49 Suppl 1:15-24. doi: 10.1111/j.1423-0410.1985.tb01139.x.
The availability of safe and effective IgG preparations for replacement therapy for patients with primary disorders of humoral immunity allows almost unlimited doses of IgG to be used. Thus, knowledge of the optimal dose and serum concentration of IgG to be achieved is of practical importance. In a multicenter study of a reduced and alkylated IgG preparation (MISG), it was shown that the MISG was well tolerated and as effective as the intramuscular immune serum globulin (ISG) used for more than 30 years. During the course of this study, we observed that the standard dose of 100 mg/kg/month resulted in a wide range of IgG levels. We began a study using another intravenous IgG preparation to determine whether the variable IgG levels were due to variability in the half-life of IgG in these patients and whether an individualized dose of IgG could be calculated based on the half-life for each patient. The half-life was greatly prolonged, ranging from 26 to 86 days compared with 21 days in normal individuals. However, there was no correlation between the half-life and the serum IgG concentration over the range of concentrations measured. When patients were treated with higher doses of IgG, based on the amount calculated to raise the serum IgG concentration to 200 mg/dl, only 1 patient actually achieved that level and only 3 had a significant increase in the serum concentration despite the higher dose. Failure to achieve the predicted levels could not be explained by a shortened half-life and seemed to be related to increased losses in the early, redistribution, phase. The half-life was not reduced in patients who did achieve higher serum IgG concentrations, suggesting that the half-life is characteristic for each patient and not directly dependent on the serum IgG concentration. However, only modest increases were observed and additional studies using much higher doses of IgG will be necessary before this issue can be settled. Similarly, we did not see an additional benefit in those patients receiving higher doses of IgG, and further studies will be necessary before it can be determined whether higher levels of IgG can reduce the incidence of chronic infections and justify the increased time and expense. The results of the completed study have been published elsewhere [7].
对于体液免疫原发性疾病患者而言，安全有效的IgG制剂可用于替代疗法，这使得几乎可以使用无限剂量的IgG。因此，了解要达到的IgG最佳剂量和血清浓度具有实际重要性。在一项关于一种经还原和烷基化处理的IgG制剂（MISG）的多中心研究中，结果表明MISG耐受性良好，且与已使用30多年的肌肉注射免疫血清球蛋白（ISG）效果相当。在这项研究过程中，我们观察到100mg/kg/月的标准剂量会导致IgG水平差异很大。我们开始使用另一种静脉注射IgG制剂进行研究，以确定IgG水平的变化是否是由于这些患者中IgG半衰期的变异性，以及是否可以根据每位患者的半衰期计算个体化的IgG剂量。半衰期大大延长，范围从26天到86天，而正常个体为21天。然而，在所测浓度范围内，半衰期与血清IgG浓度之间没有相关性。当根据计算将血清IgG浓度提高到200mg/dl的量给予患者更高剂量的IgG时，只有1例患者实际达到了该水平，尽管剂量更高，但只有3例患者血清浓度有显著升高。未能达到预测水平无法用半衰期缩短来解释，似乎与早期再分布阶段损失增加有关。达到较高血清IgG浓度的患者半衰期并未缩短，这表明半衰期是每位患者的特征，并不直接依赖于血清IgG浓度。然而，仅观察到适度增加，在这个问题得到解决之前，需要使用更高剂量的IgG进行更多研究。同样，我们在接受更高剂量IgG的患者中未看到额外益处，在确定更高水平的IgG是否可以降低慢性感染发生率并证明增加的时间和费用合理之前，还需要进一步研究。完整研究的结果已在其他地方发表[7]。
