人类免疫系统在对化学物质（包括纳米材料）的病理反应中的作用被确定为当前危害评估的一项差距。然而，人类免疫系统的复杂性以及种间变异使得开发预测毒性检测变得具有挑战性。在本研究中，我们分析了不同个体补体系统波动在免疫学检测标准化中的影响程度。我们处理了来自健康男性的商业可获得的混合血清（PS），健康捐献者和患有癌症，免疫缺陷和过敏症的个体血清并利用小分子和脂质体进行了处理。酶联免疫吸附实验测量的iC3b蛋白水平的变化作为补体激活的生物标志。PS中的补体活化水平与个体受试者的反应显著不同（p < 0.01）。健康捐献者中只有7个人对混合血清做出了类似的反应。当调查预先存在病理的捐献者血清中的脂质体对补体激活的影响时，这种变异更为显著。26个过敏捐献者的血清以及16个免疫缺陷者的血清与健康捐献者的PS的反应都不同。与处理脂质体的PS相比，过敏患者的iC3b水平增加了4.16倍。我们的研究表明，使用混合血清可能会导致对于预先存在病理的个体的免疫反应过高或过低的估计。当开发基于纳米材料的医疗产品时，这具有高度的相关性，并要求重新审视当前使用健康捐献者的PS来预测药物在患者中的免疫影响的实践。了解个体对于外来毒物的毒理学反应应该是安全评估的重要组成部分。

The role of the human immune system in pathologic responses to chemicals including nanomaterials was identified as a gap in current hazard assessments. However, the complexity of the human immune system as well as interspecies variations make the development of predictive toxicity tests challenging. In the present study, we have analysed to what extent fluctuations of the complement system of different individuals will have an impact on the standardisation of immunological tests.We treated commercially available pooled sera (PS) from healthy males, individual sera from healthy donors and from patients suffering from cancer, immunodeficiency and allergies with small molecules and liposomes. Changes of iC3b protein levels measured in enzyme-linked immunosorbent assays served as biomarker for complement activation.The level of complement activation in PS differed significantly from responses of individual donors (p < 0.01). Only seven out of 32 investigated sera from healthy donors responded similarly to the pooled serum. This variability was even more remarkable when investigating the effect of liposomes on the complement activation in sera from donors with pre-existing pathologies. Neither the 26 sera of donors with allergies nor sera of 16 donors with immunodeficiency responded similar to the PS of healthy donors. Allergy sufferers showed an increase in iC3b levels of 4.16-fold changes when compared to PS treated with liposomes.Our studies demonstrate that the use of pooled serum can lead to an over- or under-estimation of immunological response in particular for individuals with pre-existing pathologies. This is of high relevance when developing medical products based on nanomaterials and asks for a review of the current practice to use PS from healthy donors for the prediction of immunological effects of drugs in patients. A better understanding of individual toxicological responses to xenobiotics should be an essential part in safety assessments.© 2023 Lipsa et al.