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个体化固有免疫反应的时变特征:生物学第五维度的探索

Personalized-Inherent Variability in a Time-Dependent Immune Response: A Look into the Fifth Dimension in Biology.

机构信息

Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

出版信息

Pharmacology. 2022;107(7-8):417-422. doi: 10.1159/000524747. Epub 2022 May 10.

Abstract

INTRODUCTION

Individualized response to the immune triggers influences the course of immune-mediated diseases and the response to immunotherapies. Both inter- and intra-subject variations occur in time-dependent dynamics of biological systems. The present study aimed to establish a model for inherent personalized-time-dependent variability in response to immune triggers.

METHODS

Male C57BL/6 mice were administered concanavalin A (ConA) and followed every 2 h for 10 h and at 24 h for serum alanine aminotransferase (ALT) levels.

RESULTS

A marked intragroup variability was noted for both the timing of the effect of ConA, the magnitude of the increase in ALT levels, and the time to peak. While in some mice, a peak level was achieved, whereas a continuous increase in liver damage was noted in others. Four mice died at different time points during the study irrespective of their liver damage, further supporting the individualized-based response to the trigger.

CONCLUSIONS

This feasibility study established a model for determining the personalized-inherent variability in a time-dependent response to the immune triggers. These results highlight the importance of considering both the time and the wide range of individualized variability in immune responses while designing personalized-based immunotherapies.

摘要

简介

对免疫触发因素的个体化反应影响免疫介导性疾病的进程和免疫疗法的反应。生物系统的时间依赖性动力学中存在着个体内和个体间的变化。本研究旨在建立一种针对免疫触发因素反应固有个体化时间依赖性变异性的模型。

方法

雄性 C57BL/6 小鼠给予刀豆蛋白 A(ConA),并在 10 小时内每 2 小时进行一次检测,在 24 小时时检测血清丙氨酸氨基转移酶(ALT)水平。

结果

ConA 作用的时间、ALT 水平升高的幅度以及达到峰值的时间,均存在明显的组内变异性。在一些小鼠中,达到了峰值水平,而在另一些小鼠中则观察到肝损伤持续增加。在研究过程中,有 4 只小鼠在不同时间点死亡,而与肝损伤无关,这进一步支持了对触发因素的个体化反应。

结论

这项可行性研究建立了一种针对免疫触发因素的时间依赖性反应中个体化固有变异性的模型。这些结果强调了在设计基于个体化的免疫疗法时,既要考虑时间因素,也要考虑免疫反应的个体化广泛变异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2799/9254286/7abef9d76556/pha-0107-0417-g01.jpg

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