The complement system is a part of innate immunity that rapidly removes invading pathogens and impaired host-cells. Activation of the complement system is balanced under homeostasis by regulators that protect healthy host-cells. Impairment of complement regulators tilts the balance, favoring activation and propagation that leads to inflammatory and autoimmune diseases. To understand the dynamics of activation and regulation, we developed a comprehensive model of complement pathways, consisting of 290 ordinary differential equations (ODEs) and 142 kinetic parameters, that describes the states of the system under homeostasis, disease, and therapy using known drugs, compstatin and eculizumab. We will present the evaluation of the states of the system using concentration-time profiles for biomarkers influenced by complement dysregulation. We will present disease-specific ODE models and the efficacies of single drugs or combinations of drugs in restoring homeostasis. These results highlight the need for personalized therapies, depending on the disease and the manifestations of a patient’s genetic profile in regulatory function.

Prof. Dimitrios Morikis