Presentations

Mathematical model of dermatomyositis immunopathogenesis

Kireev B.V.¹, Nikitich A.N.³, Sokolov V.V., Peskov K.V.³, Volkova A.A.

G.I. Marchuk Institute of Computational Mathematics of the Russian Academy of Sciences (INM RAS), Moscow

¹Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow

²SimurgFarm LLC, Moscow

³I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow

⁴Sirius University of Science and Technology (Sirius Univeristy), Sochi

Dermatomyositis is a chronic autoimmune disease characterized by distinct cutaneous manifestations and muscular tissue involvement [1]. Among currently approved therapies, there are no targeted drugs available, which significantly reduces the proportion of patients responding to treatment [2]. The aim of this work was to develop a mathematical model of the immune processes in dermatomyositis that would help identify new biological targets in its pathogenesis.

Based on biological data, a system of ordinary differential equations (ODEs) was constructed. To determine the steady‑state concentrations of immune cells and cytokines in the plasma of patients, a systematic literature review and meta‑analysis were performed using the “metafor” package in R (version 4.3.3). A sequential approach was applied for model parameter calibration: 17 parameters were fixed based on literature data, 14 parameters were estimated from in vitro/in vivo experiments, and 10 parameters were derived from the model’s steady‑state conditions.

The developed model describes the key mechanisms of dermatomyositis pathogenesis in a subgroup of patients without interstitial lung disease under steady‑state conditions. The system of 12 ODEs reflects dermatomyositis pathogenesis as well as the pharmacokinetics of rituximab and its effect on B‑cell depletion. Sensitivity analysis revealed a significant influence of IL‑21 and CD40L on creatine kinase levels, suggesting their potential as therapeutic targets. Validation of the model on independent data from a clinical trial (NCT00106184) demonstrated that the model adequately describes B‑cell depletion induced by rituximab and the associated dynamics of muscle enzymes.

This work was supported by the Russian Science Foundation grant 23‑71‑10051.

References:

[1] Krathen M. S., Fiorentino D., Werth V. P. Dermatomyositis. – Current directions in autoimmunity, 2008, vol. 10, pp. 313.

[2] Guo J. et al. Pharmacological Strategies in Dermatomyositis: Current Treatments and Future Directions // Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 2024, vol. 30, pp. e944564‑1.

• abstract in Russian (PDF)