The following is a summary of “Unveiling chronic spontaneous urticaria pathophysiology through systems biology,” published in the APRIL 2023 issue of Allergy & Immunology by Vergés, et al.
For a study, researchers sought to model the pathophysiology of chronic spontaneous urticaria (CSU) and utilize in silico analysis to identify the mechanisms of action of various therapeutic strategies currently used or under development for CSU.
A therapeutic performance mapping system technology, combining systems biology and machine learning, was employed to construct a CSU interactome. The interactome was validated using gene expression data from CSU patients. A CSU model was then created to investigate CSU pathophysiology and evaluate the mechanisms of action of different therapeutic strategies.
The models successfully captured the established role of mast cell activation as a central process in CSU pathophysiology. They also revealed the involvement of various therapeutic strategies in innate and adaptive immune processes. For instance, anti-IgE and Bruton tyrosine kinase inhibitors directly affected mast cell biology by inhibiting FcεRI signaling activity.
On the other hand, anti-interleukins and anti–Siglec-8 were observed to modulate adaptive immunity. The in silico CSU models generated in the study accurately reproduced known features of CSU and the mechanisms of action of different therapeutic strategies. The findings contributed to a deeper understanding of the therapeutic mechanisms involved in CSU and have the potential to advance personalized treatment approaches based on patient profiles.