Dynamically modeling the effective range of IL-2 dosage in the treatment of systemic lupus erythematosus.
Dynamically modeling the effective range of IL-2 dosage in the treatment of systemic lupus erythematosus.
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DOI：
10.1016/j.isci.2022.104911
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发表时间：
2022-09-16
期刊：
影响因子：
5.8
通讯作者：
Li, Fangting
中科院分区：
文献类型：
--
作者：
Gao, Xin;He, Jing;Sun, Xiaolin;Li, Fangting
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过度免疫反应。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，低剂量白介素-2 （IL-2）治疗SLE有效。在这里，我们建立了一个涉及Tcons、Tregs、自然杀伤（NK）细胞和IL-2的数学模型来模拟SLE治疗的动态过程。我们发现了由Tcon/Treg比值定义的SLE治疗中IL-2剂量的有效范围，称为IL-2剂量治疗窗口（IDTW）。我们的研究结果表明，高水平的自身抗原导致较窄的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细胞比例的分类方法来预测SLE患者的治疗结果。Tcon/Treg比值可作为定义SLE治疗中IL-2剂量治疗窗口的指标。自体抗原水平高的SLE患者IL-2治疗窗口预计较窄。高剂量的IL-2会过度激活Tcon，增加SLE患者的Tcon/Treg比值。生物信息学;数学生物科学
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. Tcon/Treg ratio can be an indicator to define the IL-2 dosage therapeutic window in SLE treatment SLE patients with high levels of self-antigen are predicted to have a narrow IL-2 therapeutic window High-dose IL-2 should overactivate Tcons and increase the Tcon/Treg ratio in SLE patients SLE patients with lower pre-treatment Treg are more likely to benefit from IL-2 administration Immunology; Bioinformatics; Mathematical biosciences
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