BarrieR Integrity loss in Gut as driver of Host tissue Tropism and outcome in PsA: the BRIGHT concept
Concept
Psoriatic arthritis (PsA) is clinically heterogeneous, showing inflammation of the peripheral joints, spine, entheses, fingers and toes, skin or nails. Whilst there is substantial overlap in the underlying immunobiology driving inflammation in any of these sites, there are also marked differences. However, the reasons for these differences are unclear. The BRIGHT consortium hypothesizes that intestinal microbiota shape immune responses in the early stages of PsA thereby driving clinical heterogeneity. To address this, the group will investigate (i) how gut barrier integrity, intestinal dysbiosis, disease subtype and severity relate in patients; (ii) whether there are differences in the cellular sources that produce or respond to IL-23 and IL-17 production, using deep phenotyping of blood, gut, joint and skin; and (iii) whether PsA intestinal microbiota shape IL-23 and/or IL-17-dependent responses and treatment, using animal models of axial and peripheral forms of PsA.
Facts and Figures
E Lubberts
Erasmus MC, University Medical Center Rotterdam
E.Lubberts@erasmusmc.nl
Meet the Team
King’s College London
VIB Center for Inflammation Research & Ghent University
Objectives
- Obj.1: How do gut barrier integrity, intestinal dysbiosis, disease subtype and severity in PsA relate?
- Obj.2: Do similar cellular sources produce or respond to IL-23 and IL-17 in different tissues (blood, skin, gut, joint) in PsA?
- Obj.3: Do intestinal microbiota shape IL-23/IL-17 dependent responses in axial and peripheral forms of PsA?
Goals/Milestones
Objective 1
- M1, months 01 – 12: Serum analysis of GIANT cohort
- M2, months 06 – 18: PsA gut histopathology
- M3, months 12 – 24: Link to microbiota and PsA phenotype
Objective 2
- M4, months 01 – 24: Patient recruitment and sample collection
- M5, months 04 – 30: Deep phenotyping by scRNAseq and flow cytometry
Objective 3
- M6, months 01 – 36: Experimental animal studies in germ-free, gnotobiotic and knockout models
- M7, months 27 – 36: Manuscript submission
- M8, months 30 – 36: Symposium
Patient Voice
Several million adults in Europe live with PsA, which significantly affects their quality of life. The group hopes that their findings will start to reveal the gut as a potential critical determinant of peripheral versus spinal disease subtype in patients with PsA. This would generate a shift in the way we think about the diagnosis, disease outcome and response to treatment in PsA.