Dynamically Modeling the Effective Range of IL-2 Dosage in the Treatment of Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by an overactive immune response to self-antigens. 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 and IL-2 to simulate the dynamic processes involved in the treatment of SLE. We found an effective range of IL-2 dosage, termed as the IL-2 dosage therapeutic window (IDTW), such that an IL-2 dose above the upper limit of IDTW overactivates Tcons and leads to treatment failure. Our results showed that high levels of self-antigen results in a narrow IDTW and high post-treatment Tcons. Furthermore, we proposed a classification method based on patients’ pretreatment Tregs to predict the patients most likely to benefit from IL-2 treatment.