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

Gao, Xiong; He, Jing; Sun, Xiaolin; Li, Fangting

doi:10.1016/j.isci.2022.104911

Cited by 4 publications

(5 citation statements)

References 38 publications

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“…As opposed to a rather qualitative assessment of drug effects in the aforementioned models, another model considered in this section was specifically designed to quantify the treatment effect of exogenous IL-2 therapy in patients with SLE ( 29 ). The model by Gao et al.…”

Section: Resultsmentioning

confidence: 99%

“…, the works of Gao et al. ( 29 ), Nakada and Mager ( 32 ), Rogers et al. ( 39 , 40 ), and Miyano et al.…”

Section: Discussionmentioning

confidence: 99%

“…Among good modeling practices, several key components could be named, e.g., extensive model calibration and evaluation, including identifiability analyses, external validation, sensitivity analyses, and more (124). Several models, e.g., the works of Gao et al (29), Nakada and Mager (32), Rogers et al (39, 40), and Miyano et al (55) feature a broad array of these technical modelbased analyses. Furthermore, these models attempt to incorporate subject inter-individual variability through the means of generating realistic virtual populations; they also consider realistic PK models of the compounds, driving the effects, which greatly expands the applicability of such models to real-world scenarios.…”

Section: Discussionmentioning

confidence: 99%

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Mathematical modeling in autoimmune diseases: from theory to clinical application

Ugolkov,

Nikitich,

Leon

et al. 2024

Front. Immunol.

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The research & development (R&D) of novel therapeutic agents for the treatment of autoimmune diseases is challenged by highly complex pathogenesis and multiple etiologies of these conditions. The number of targeted therapies available on the market is limited, whereas the prevalence of autoimmune conditions in the global population continues to rise. Mathematical modeling of biological systems is an essential tool which may be applied in support of decision-making across R&D drug programs to improve the probability of success in the development of novel medicines. Over the past decades, multiple models of autoimmune diseases have been developed. Models differ in the spectra of quantitative data used in their development and mathematical methods, as well as in the level of “mechanistic granularity” chosen to describe the underlying biology. Yet, all models strive towards the same goal: to quantitatively describe various aspects of the immune response. The aim of this review was to conduct a systematic review and analysis of mathematical models of autoimmune diseases focused on the mechanistic description of the immune system, to consolidate existing quantitative knowledge on autoimmune processes, and to outline potential directions of interest for future model-based analyses. Following a systematic literature review, 38 models describing the onset, progression, and/or the effect of treatment in 13 systemic and organ-specific autoimmune conditions were identified, most models developed for inflammatory bowel disease, multiple sclerosis, and lupus (5 models each). ≥70% of the models were developed as nonlinear systems of ordinary differential equations, others – as partial differential equations, integro-differential equations, Boolean networks, or probabilistic models. Despite covering a relatively wide range of diseases, most models described the same components of the immune system, such as T-cell response, cytokine influence, or the involvement of macrophages in autoimmune processes. All models were thoroughly analyzed with an emphasis on assumptions, limitations, and their potential applications in the development of novel medicines.

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Section: Resultsmentioning

confidence: 99%

“…, the works of Gao et al. ( 29 ), Nakada and Mager ( 32 ), Rogers et al. ( 39 , 40 ), and Miyano et al.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mathematical modeling in autoimmune diseases: from theory to clinical application

Ugolkov,

Nikitich,

Leon

et al. 2024

Front. Immunol.

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“… 2010 ), focus on treatment strategies based on IL-2 for the chronic stage (Gao et al. 2022 ), or model the pathophysiology (kidney injury) in the case of lupus nephritis (Hao et al. 2014 ).…”

Section: Discussionmentioning

confidence: 99%

“… 2010 ; Gao et al. 2022 ), study organ damage in the case of Lupus nephritis (Hao et al. 2014 ), or work with aggregate features of the disease without elucidating the mechanisms behind its pathophysiology (Yazdani et al.…”

Section: Introductionmentioning

confidence: 99%

Modelling the Impact of NETosis During the Initial Stage of Systemic Lupus Erythematosus

Suvandjieva,

Tsacheva,

Santos

et al. 2024

Bull Math Biol

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The development of autoimmune diseases often takes years before clinical symptoms become detectable. We propose a mathematical model for the immune response during the initial stage of Systemic Lupus Erythematosus which models the process of aberrant apoptosis and activation of macrophages and neutrophils. NETosis is a type of cell death characterised by the release of neutrophil extracellular traps, or NETs, containing material from the neutrophil’s nucleus, in response to a pathogenic stimulus. This process is hypothesised to contribute to the development of autoimmunogenicity in SLE. The aim of this work is to study how NETosis contributes to the establishment of persistent autoantigen production by analysing the steady states and the asymptotic dynamics of the model by numerical experiment.

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In vitro modulation of T cells in myasthenia gravis by low‐dose IL‐2

Çebi,

Çakar,

Durmuş

et al. 2024

Eur J Immunol

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Follicular helper (Tfh), peripheral helper (Tph), and regulatory (Treg) T cells are involved in myasthenia gravis (MG) pathogenesis, an autoimmune disorder arising from autoantibodies targeting neuromuscular junction proteins. This study explores the impact of low‐dose IL‐2 on Tfh, Tph, and Treg cells in vitro in MG. Acetylcholine‐receptor antibody‐positive MG (AChR‐MG), muscle‐specific kinase antibody‐positive MG (MuSK‐MG) patients, and healthy controls (HC) were studied. Blood cells were cultured with/without IL‐2 and compared by the ratios of IL‐2 stimulated/unstimulated cultures. In both AChR‐MG and MuSK‐MG patients, CD25+FoxP3+Tregs were lower, while CXCR5+PD‐1+ or ICOS+Tfh and CXCR5−PD‐1+ or ICOS+Tph cells were higher compared with HC. Among the MG group, the FoxP3+ Treg cells in AChR‐MG patients were even lower compared with MuSK‐MG patients. In vitro IL‐2 stimulation increased Tregs in all groups while decreasing PD‐1+/ICOS+Tfh and PD‐1+/ICOS+Tph populations. The fold‐increase ratio of Tregs and the fold‐decrease ratio of PD‐1+ or ICOS+Tfh and ICOS+Tph cells in AChR‐MG and MuSK‐MG patients were greater than in HCs. Low‐dose IL‐2 treatment may balance Tfh, Tph, and Treg cells in MG patients, offering a potential opportunity for disease modulation.

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

Cited by 4 publications

References 38 publications

Mathematical modeling in autoimmune diseases: from theory to clinical application

Mathematical modeling in autoimmune diseases: from theory to clinical application

Modelling the Impact of NETosis During the Initial Stage of Systemic Lupus Erythematosus

In vitro modulation of T cells in myasthenia gravis by low‐dose IL‐2

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