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Background: Juvenile idiopathic arthritis (JIA) is an umbrella term used to describe a group of chronic arthritides of unknown cause in children and adolescents. It is the most common rheumatic disease in children and young people under the age of 16, and if left untreated can cause significant morbidity. Oligoarthritis is the most common of the seven different JIA subtypes and is characterized by autoantibody production and the differentiation of autoreactive T cells. B lymphocytes are known to contribute to the pathophysiology of oligoarthritis by producing autoantibodies, but recent developments suggest that they may further contribute to disease by presenting auto-antigens to (autoreactive) T cells, or secreting by cytokines that influence the function of other inflammatory cell types. Objectives: To carry out in-depth immunophenotyping of B cells in the peripheral blood (PB) and synovial fluid (SF) of patients with oligoarthritis. Greater understanding into the phenotype and function of B lymphocytes in oligoarthritis may help clinicians identify novel treatment targets for patients that fail first-line methotrexate therapy. Methods: Patients with oligoarthritis (n=28, age 0-15), adult healthy controls (n=4, age>21) and child healthy controls (n=3, age 7-15) were included in this study. All patients and controls were recruited in the United Kingdom with fully informed and age-appropriate consent as approved by the London-Bloomsbury Research Ethics Committee (ref: 95RU04) in accordance with the Declaration of Helsinki. PB and SF mononuclear cells were prepared by density centrifugation and immunophenotyped by flow cytometry. Results: CD19+CD24loCD38lo (atypical) and CD19+CD2hiCD38lo (memory) B cells were enriched in synovial fluid compared to peripheral blood, whereas CD19+CD24hiCD38hi (immature) and CD19+CD24intCD38int (mature) B cells were depleted. The B cell activation markers CD27 and CD86 were also found to be upregulated on SF B cells compared to PB B cells. Further analysis using extracellular markers identified by single cell sequencing analysis revealed that SF B cells also express higher levels of complement receptor 4 (CD11c/CD18) and the oxysterol receptor GPR183 than PB B cells. Conclusion: Flow cytometry analysis demonstrated that B cells in the synovial fluid have a distinct phenotype compared to B cells in the peripheral blood. Future work will investigate the functional implications of these results. Acknowledgement: This research was funded by Versus Arthritis, Great Ormond Street Children’s Charity, UCL Partners, the National Institute for Health Research (NIHR) UCL Hospitals Biomedical Research Centre, and NIHR- Great Ormond Street Biomedical Research Centre. Disclosure of Interests: None declared |
