SAT0354 TYPE 3 INNATE LYMPHOID CELLS ARE KEY DRIVERS OF PSORIATIC ARTHRITIS
Authors: M. G. Raimondo, S. Rauber, M. Luber, A. Rius Rigau, S. Weber, C. G. Anchang, R. Agarwal, A. Soare, M. Sticherling, J. Rech, A. Kleyer, J. Distler, G. Schett, A. Ramming
Journal: Annals of the Rheumatic Diseases (2020)

Background: Psoriasis (PsO) and psoriatic arthritis (PsA) are two types of chronic inflammatory diseases that share a similar cytokines profile. About 30% of PsO patients also develop a joint involvement, but the underlying mechanism is still unclear. Innate lymphoid cells (ILC) and specifically the type 3 ILCs (ILC3s) have raised increasing interest as possible player in the pathogenesis of both diseases, as they produce the pathological key cytokine IL-17A. Objectives: We addressed the contribution of ILC3s to the pathogenesis of PsO and PsA in patients as well as murine in vivo models. Methods: 130 patients satisfying the Classification Criteria for Psoriatic Arthritis (CASPAR), 40 patients with PsO and 35 healthy volunteers were enrolled in the study. Information regarding clinical features, laboratory parameters were collected and psoriasis area severity index (PASI), disease activity score 28 (DAS28), disease activity in psoriatic arthritis (DAPSA), minimal disease activity score (MDA) were calculated. Magnetic resonance imaging (MRI) and high-resolution peripheral CT (HR-pQCT) were taken and PsA MRI score (PsAMRIS) was assessed. Flow cytometric analysis was performed and IFNγ-producing ILC1s, IL-4/IL-5-producing ILC2s and IL-17/IL-22-producing ILC3s were identified among ILCs. Multivariate linear regression and Receiver-Operating Characteristic (ROC) Curve analysis was performed using the IBM SPSS Statistics software. Different in vivo models were used to assess functional implications of ILCs at different time points of the disease. Joint inflammation was assessed through MRI and H&amp;E staining of ankle areas. Peripheral blood was obtained from mice of each group and flow cytometry analysis was performed. High dimensional analyses including RNA-seq was performed to identify phenotypic characteristics of ILCs implemented into the pathogenesis of the disease. Results: Total number of circulating ILCs were increased in PsA patients compared to PsO and healthy controls (p&lt;0,001). Linear regression analyses of the relationship between disease activity and circulating ILCs counts showed strongest correlation between ILC3s counts and DAPSA score. ILC3s counts also correlated with imaging signs of inflammation such as enthesitis, synovitis, erosions and/or ostoeproliferation as assessed by MRI and HR-pQCT. Musculoskeletal inflammation in mice was predominantly associated with p19 expression and IL-23R-signaling as assessed by RNA-seq. These effects were also accompanied by a strong upregulation of IL-17-producing lymphocytes within the inflamed joint niche with a dominant presence of ILC3s. Multi-channel immunofluorescence and confocal laser scanning microscopy revealed not only upregulation of ILC3 induced IL-17 production within the synovial membrane but also in peri-articular areas of the inflamed joints. Conclusion: ILC3s not only correlate with various facets of PsA manifestations but also functionally contribute to synovitis and enthesitis suggesting them as interesting target for upcoming treatment strategies in the near future. Disclosure of Interests: Maria Gabriella Raimondo Grant/research support from: Celgene, Partner Fellowship, Simon Rauber: None declared, Markus Luber: None declared, Aleix Rius Rigau: None declared, Stefanie Weber: None declared, Charles Gwellem Anchang: None declared, Rahul Agarwal: None declared, Alina Soare: None declared, Michael Sticherling Grant/research support from: Novartis, Consultant of: Advisory boards Abbvie, Celgene, Janssen Cilag, Lilly, Pfizer, MSD, Novartis, Amgen, Leo, Sanofi, UCB, Speakers bureau: Abbvie, Celgene, Janssen Cilag, Leo, MSD, Novartis, Pfizer, Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Jörg Distler Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Andreas Ramming Grant/research support from: Pfizer, Novartis, Consultant of: Boehringer Ingelheim, Novartis, Gilead, Pfizer, Speakers bureau: Boehringer Ingelheim, Roche, Janssen