The key unmet clinical needs in Psoriasis (PsO) and Psoriatic Arthritis (PsA) management include (i) prognostic biomarkers of progression from PsO-to-PsA and (ii) improved understanding of pathogenic mechanisms of transition from skin-to-joint disease. Provision of these will lead to earlier diagnosis and treatment – with better prognosis – of PsA, and aid development of novel drug targets which prevent rather than treat PsA. This project aims to uncover heterogeneity of PsO/PsA by establishing its comprehensive functional cellular and molecular atlas of blood, skin and synovium, and to uncover the mechanisms and biomarkers of the evolution from PsO-to-PsA. This aim will be addressed by an international team of clinical and basic science researchers with synergistic patient cohorts, tissue biopsy repository and diverse computational and experimental expertise.
A) To delineate the cellular and molecular atlas of the disease trajectory from PsO-to-PsA using single cell multi-omic profiling.
B) To investigate the role of candidate PsO/PsA shared cell clusters/pathways in initiating joint pathologies by using in vitro synovial organoids or tissue digests with pathway inhibitors.
C) To identify the biomarkers of progression from PsO-to-PsA by integrating the cellular atlas of PsO with longitudinal clinical outcomes (including PsA development or not).
Milestone 1: Providing candidate pathways determining the transition from PsO-to-PsA.
Milestone 2: Identification of the molecular mechanisms of PsO-to-PsA transition.
Milestone 3: Identification of the Biomarkers of PsO-to-PsA transition.
Kurowska-Stolarska, M., Alivernini, S. Synovial tissue macrophages in joint homeostasis, rheumatoid arthritis and disease remission. Nat Rev Rheumatol 18, 384–397 (2022). https://doi.org/10.1038/s41584-022-00790-8
This project will help identify at-risk PsO patients for earlier diagnosis of PsA, and improve treatment options of patients with PsA. If the biomarkers of PsOto-PsA transition identified in this study are confirmed by other Rheumatology centres across the world, this can lead to a change of EULAR treatment recommendation for PsO patients to favour earlier drug intervention.
In addition, this project will provide new knowledge on the mechanisms of PsO-to-PsA transition.