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Low CD73 expression on synovial lymphocytes correlates with reduced adenosine generation and higher disease severity in juvenile idiopathic arthritis

Botta Gordon-Smith, SL; Ursu, S; Eaton, S; Moncrieffe, H; (2014) Low CD73 expression on synovial lymphocytes correlates with reduced adenosine generation and higher disease severity in juvenile idiopathic arthritis. Arthritis and Rheumatism , 67 (2) pp. 545-554. 10.1002/art.38959. Green open access

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Abstract

Objective To investigate the expression and the adenosine-generating activity of the ecto-5'-nucleotidase CD73 on synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) from children with arthritis. Methods Given the role of CD73 protein in the production of anti-inflammatory adenosine which intersects with inflammatory biology, its expression on lymphocytes was determined by flow cytometry. The CD73 AMPase activity of PBMC and SFMC was measured by HPLC. The effects of cell activation on CD73 expression were examined by in vitro culture of PBMC. Results CD8+ and CD19+ synovial lymphocytes from patients with juvenile idiopathic arthritis (JIA) expressed decreased levels of CD73 compared to both paired JIA PBMC and those from healthy controls. When comparing percentages of CD73+ synovial fluid lymphocytes in the two clinical forms of oligoarthritis, those with extended oligoarthritis showed lower CD73 expression compared to patients with the milder form of disease. Synovial CD8+ T cells had a lower ability to produce adenosine from Etheno-AMP compared to CD8+ PBMC. T cell activation through the TCR of CD8+CD73+ cells and B cell activation through TLR9 resulted in reduced expression of CD73. This downregulation occurred on dividing cells. Conclusion These data show that low CD73 expression on T and B cells in the inflammatory site is related to cell proliferation and is correlated with the clinical severity of oligoarticular JIA. The decreased CD73 expression on SFMC in turn results in reduced adenosine production, which would lead to decreased potential for anti-inflammatory activity.

Type: Article
Title: Low CD73 expression on synovial lymphocytes correlates with reduced adenosine generation and higher disease severity in juvenile idiopathic arthritis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/art.38959
Publisher version: http://dx.doi.org/10.1002/art.38959
Language: English
Additional information: © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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 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 > Developmental Biology and Cancer Dept
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/1456634
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