The considerable variability of responses amongst subjects to disease triggers and immunotherapies is a major obstacle to designing better immune-based therapies. Therefore, development of patient-tailored precision medicine that improves the efficacy of immunomodulatory drugs is necessary. The individualized response to disease triggers and immunomodulatory therapies was studied using the concanavalin A (ConA) immune-mediated hepatitis model and the oral administration of anti CD3 or β-glucosylceramide (GC). Mice were treated with anti-CD3 antibodies or GC followed by an injection of ConA. The effects of these treatments on liver damage and the immune profile were then analyzed. An individualized response to ConA and orally administered immunomodulatory agents was observed in eight consecutive experiments. While alleviation of the immune-mediated liver injury, as measured by serum levels of liver enzymes, was seen, and high intra-group and inter-experimental variabilities were detected. A similar individualized response was observed for the effect on serum levels of IFN-γ, TNF-α, and IL-10 and on CD4+CD25+, CD8+CD25+, and CD3+NK1.1+ lymphocytes. A personalized form of inherent randomness in an isolated system was documented, which may underlie the variability in responses to immune triggers and immunomodulatory therapies. The data support the use of personalized randomness-based platforms for improving the response to chronic therapies.

中文翻译：

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免疫系统的个性化固有随机性表现为对免疫触发和免疫调节疗法的个性化反应：设计个性化免疫疗法的新型平台。

受试者对疾病触发因素和免疫疗法的反应差异很大，这是设计更好的基于免疫疗法的主要障碍。因此，需要开发针对患者的精密药物，以提高免疫调节药物的功效。使用伴刀豆球蛋白A（ConA）免疫介导的肝炎模型和口服抗CD3或β-葡萄糖基神经酰胺（GC），研究了对疾病触发因素和免疫调节疗法的个体反应。用抗CD3抗体或GC治疗小鼠，然后注射ConA。然后分析了这些治疗对肝损伤和免疫特性的影响。在八个连续的实验中观察到对ConA和口服免疫调节剂的个体反应。虽然可以观察到由肝酶的血清水平所测量的免疫介导的肝损伤的减轻，并且检测到高的组内和实验间变异性。对于IFN-γ，TNF-α和IL-10的血清水平以及对CD4 + CD25 +，CD8 + CD25 +和CD3 + NK1.1 +淋巴细胞的影响，观察到类似的个体化反应。已记录了隔离系统中固有随机性的个性化形式，这可能是对免疫触发和免疫调节疗法反应的可变性的基础。数据支持使用基于个性化随机性的平台来改善对慢性疗法的反应。对于IFN-γ，TNF-α和IL-10的血清水平以及对CD4 + CD25 +，CD8 + CD25 +和CD3 + NK1.1 +淋巴细胞的影响，观察到类似的个体化反应。已记录了隔离系统中固有随机性的个性化形式，这可能是对免疫触发和免疫调节疗法反应的可变性的基础。数据支持使用基于个性化随机性的平台来改善对慢性疗法的反应。对于IFN-γ，TNF-α和IL-10的血清水平以及对CD4 + CD25 +，CD8 + CD25 +和CD3 + NK1.1 +淋巴细胞的影响，观察到类似的个体化反应。已记录了隔离系统中固有随机性的个性化形式，这可能是对免疫触发和免疫调节疗法反应的可变性的基础。数据支持使用基于个性化随机性的平台来改善对慢性疗法的反应。