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Biologic Predictors of Extension of Oligoarticular Juvenile Idiopathic Arthritis as Determined From Synovial Fluid Cellular Composition and Gene Expression

Hunter, PJ; Nistala, K; Jina, N; Eddaoudi, A; Thomson, W; Hubank, M; Wedderburn, LR; (2010) Biologic Predictors of Extension of Oligoarticular Juvenile Idiopathic Arthritis as Determined From Synovial Fluid Cellular Composition and Gene Expression. Arthritis and Rheumatism , 62 (3) pp. 896-907. 10.1002/art.27284. Green open access

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Abstract

Objective: To identify biomarkers in the first synovial fluid (SF) aspirate obtained from children with oligoarticular juvenile idiopathic arthritis (JIA), which could be used to identify children whose disease is likely to extend to a more severe phenotype. Methods: Patients with recent‐onset oligoarticular JIA were identified and grouped according to those whose mild disease persisted (persistent disease) or those whose disease would extend from a mild to more severe phenotype (extended‐to‐be disease) at 1 year after diagnosis. Flow cytometry was used to delineate differences in the mononuclear cell populations between the first blood sample and first SF aspirate from the same patient and between outcome (persistent versus extended‐to‐be) groups. Proportions of lymphocytes in the joint were modeled on chemotaxis of lymphocytes to CCL5, using Transwell migration assays. Levels of CCL5 in the SF were quantified by enzyme‐linked immunosorbent assay. RNA profiles of SF mononuclear cells were compared between groups using the Affymetrix GeneChip hybridization protocol and hierarchical clustering analyses. Results: Compared with peripheral blood mononuclear cells, SF mononuclear cells displayed an expansion of CD8+ T cells, reduced proportion of B cells, and expansion of CD16− natural killer cells. The lower CD4:CD8 ratio in the SF was recapitulated in vitro by the observed migration of blood T cells in response to CCL5. Synovial CCL5 levels were higher in children whose disease extended to a more severe phenotype. The CD4:CD8 ratio in the SF was significantly lower in patients with extended‐to‐be oligoarticular JIA (0.57 compared with 0.90 in the persistent disease group, difference 0.33, 95% confidence interval 0.04–0.62; P = 0.009). Gene expression profiling revealed that 344 genes were >1.5‐fold differentially expressed between outcome groups (P < 0.05), and these included genes associated with inflammation and macrophage differentiation, which showed increased levels in patients with extended disease at 1 year, and genes associated with immune regulation, which showed increased levels in patients with persistent disease at 1 year. Conclusion: Analyses of the proportions of synovial lymphocytes, levels of CCL5, and differential gene expression yielded potential biomarkers with which to predict the likelihood of extension of oligoarticular JIA to a more severe disease phenotype.

Type: Article
Title: Biologic Predictors of Extension of Oligoarticular Juvenile Idiopathic Arthritis as Determined From Synovial Fluid Cellular Composition and Gene Expression
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/art.27284
Publisher version: https://doi.org/10.1002/art.27284
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10111448
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