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.
Project Lead
M Kurowska-StolarskaA) 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
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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.