SAT0496 INTERROGATING THE CIRCULATORY IMMUNE ARCHITECTURE OF ENTHESITIS-RELATED ARTHRITIS

• Published in: Annals of the rheumatic diseases Vol. 79; no. Suppl 1; p. 1204
• Main Authors: Tay, S. H., Leong, J. Y., Wasser, M., Lim, A. J. M., Chen, P., Yeo, J. G., Arkachaisri, T., Albani, S.
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2020
• Subjects: Arthritis; CD4 antigen; Cytometry; Disease; Gating; Leukocytes (mononuclear); Lymphocytes T; Microenvironments; Pathogenesis; Patients; Pediatrics; Peripheral blood mononuclear cells; Rheumatology; Sacroiliitis
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2020-eular.5125

Background: Enthesitis-related arthritis (ERA) is one of the most common subtype of juvenile idiopathic arthritis (JIA) in Asia 1 . It carries a poor prognosis, but limited knowledge of its pathogenesis hampers clinical diagnosis and treatment. Objectives: We hypothesise multiple aberrations from the healthy immunome culminating in an imbalance between the immune effector and regulatory cell subsets as key for driving ERA pathogenesis. Thus, we employed a comprehensive high-dimensional interrogative strategy using mass cytometry to assess the ERA immune architecture 2 . Methods: We examined peripheral blood mononuclear cells from 30 ERA patients (15 with active sacroilitis, 15 without active sacroilitis) within the first two years of disease and 30 healthy paediatric controls with mass cytometry, using two extensive antibody panels encompassing key lineage and functional markers. Dimensional reduction and unsupervised clustering were performed to identify immune cell subsets differentially present in ERA patients. Manual gating was performed to further describe observed differences in subset frequencies. These subsets were statistically evaluated with reference to the healthy cohort and their association with disease activity determined. Results: We identified broad differences in the ERA circulatory immune architecture that involved both innate and adaptive immune cell populations, notably with the enrichment of naive CD4+ T cells as well as depletion of cytolytic NK cells (CD56 dim CD16+). The chemotactic profiles of their subsets also differed in ERA patients, which underscores their migratory capacity and hence potential effector role in the ERA arthritic microenvironment. In addition, there were some dissimilarities in the circulatory immunome of ERA patients with active sacroiliitis as compared to those without, which alludes to a possible mechanistic basis behind the disease complication. Conclusion: This is the first study, via deep parameterisation afforded by mass cytometry, to demonstrate a concomitant dysregulation of both innate and adaptive immune cell subsets in ERA patients. Further mechanistic studies of these immune cell subsets and their functional networks will inform the development of diagnostic and prognostic markers that can reliably predict clinical fate in ERA, thereby complementing clinical assessment in the care of ERA patients. References: [1]Arkachaisri et al. Paediatric rheumatology clinic in Southeast Asia: are we different? Rheumatology (Oxford ). 2017. [2]Tay et al. Immunomics in pediatric rheumatic diseases. Front Med (Lausanne ). 2019. Disclosure of Interests: None declared