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动态模拟白细胞介素-2剂量在系统性红斑狼疮治疗中的有效范围。

Dynamically modeling the effective range of IL-2 dosage in the treatment of systemic lupus erythematosus.

作者信息

Gao Xin, He Jing, Sun Xiaolin, Li Fangting

机构信息

Center for Quantitative Biology, Peking University, Beijing 100871, China.

School of Physics, Peking University, Beijing 100871, China.

出版信息

iScience. 2022 Aug 11;25(9):104911. doi: 10.1016/j.isci.2022.104911. eCollection 2022 Sep 16.

Abstract

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by an overactive immune response to self-antigen. The overactivation of CD4 Foxp3 conventional T cells (Tcons) and the inactivation of CD4 CD25 Foxp3 regulatory T cells (Tregs) play important roles in the progression of SLE. Clinical trials showed that low-dose interleukin-2 (IL-2) is effective in treating SLE. Here, we developed a mathematical model involving Tcons, Tregs, natural killer (NK) cells, and IL-2 to simulate the dynamic processes involved in the treatment of SLE. We found an effective range of IL-2 dosage defined by the Tcon/Treg ratio in SLE treatment, termed the IL-2 dosage therapeutic window (IDTW). Our results showed that high levels of self-antigen result in a narrow IDTW and high post-treatment Tcon/Treg ratio. Furthermore, we proposed a classification method based on the ratio of pre-treatment Treg to CD4 T cells to predict the treatment outcome of SLE patients.

摘要

系统性红斑狼疮(SLE)是一种复杂的系统性自身免疫性疾病,其特征是对自身抗原的免疫反应过度活跃。CD4 Foxp3常规T细胞(Tcons)的过度激活和CD4 CD25 Foxp3调节性T细胞(Tregs)的失活在SLE的进展中起重要作用。临床试验表明,低剂量白细胞介素-2(IL-2)对治疗SLE有效。在此,我们建立了一个涉及Tcons、Tregs、自然杀伤(NK)细胞和IL-2的数学模型,以模拟SLE治疗中涉及的动态过程。我们发现了SLE治疗中由Tcon/Treg比率定义的IL-2剂量有效范围,称为IL-2剂量治疗窗口(IDTW)。我们的结果表明,高水平的自身抗原会导致较窄的IDTW和较高的治疗后Tcon/Treg比率。此外,我们提出了一种基于治疗前Treg与CD4 T细胞比率的分类方法,以预测SLE患者的治疗结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d97e/9429801/2da592f2a18f/fx1.jpg

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