Individualised computational modelling of immune mediated disease onset, flare and clearance in psoriasis
Authors: Shmarov Fedor , Smith Graham R. , Weatherhead Sophie C. , Reynolds Nick J. , Zuliani Paolo 
Published: September 2021

Despite increased understanding about psoriasis pathophysiology, currently there is a lack of predictive computational models. We developed a personalisable ordinary differential equations model of human epidermis and psoriasis that incorporates immune cells and cytokine stimuli to regulate the transition between two stable steady states of clinically healthy (non-lesional) and disease (lesional psoriasis, plaque) skin. In line with experimental data, an immune stimulus initiated transition from healthy skin to psoriasis and apoptosis of immune and epidermal cells induced by UVB phototherapy returned the epidermis back to the healthy state. Notably, our model was able to distinguish disease flares. The flexibility of our model permitted the development of a patient-specific “UVB sensitivity” parameter that reflected subject-specific sensitivity to apoptosis and enabled simulation of individual patients’ clinical response trajectory. In a prospective clinical study of 94 patients, serial individual UVB doses and clinical response (Psoriasis Area Severity Index) values collected over the first three weeks of UVB therapy informed estimation of the “UVB sensitivity” parameter and the prediction of individual patient outcome at the end of phototherapy. An important advance of our model is its potential for direct clinical application through early assessment of response to UVB therapy, and for individualised optimisation of phototherapy regimes to improve clinical outcome. Additionally by incorporating the complex interaction of immune cells and epidermal keratinocytes, our model provides a basis to study and predict outcomes to biologic therapies in psoriasis.

Author Summary

We present a new computer model for psoriasis, an immune-mediated disabling skin disease which presents with red, raised scaly plaques that can appear over the whole body. Psoriasis affects millions of people in the UK alone and causes significant impairment to quality of life, and currently has no cure. Only a few treatments (including UVB phototherapy) can induce temporary remission. Despite our increased understanding about psoriasis, treatments are still given on a ‘trial and error’ basis and there are no reliable computer models that can a) elucidate the mechanisms behind psoriasis onset or flare and b) predict a patient’s response to a course of treatment (e.g., phototherapy) and the likelihood of inducing a period of remission. Our computer model addresses both these needs. First, it explicitly describes the interaction between the immune system and skin cells. Second, our model captures response to therapy at the individual patient level and enables personalised prediction of clinical outcomes. Notably, our model also supports prediction of amending individual UVB phototherapy regimes based on the patient’s initial response that include for example personalised delivery schedules (i.e., 3x weekly vs. 5x weekly phototherapy). Therefore, our work is a crucial step towards precision medicine for psoriasis treatment.