Rheumatology Advance Access originally published online on February 28, 2003
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Rheumatology 2003; 42: 583-590
© 2003 British Society for Rheumatology
Paediatric Rheumatology |
Synovial dendritic cells in juvenile idiopathic arthritis (JIA) express receptor activator of NF-
B (RANK)
Rheumatology Unit, Institute of Child Health, University College London and Great Ormond Street Hospital for Children NHS Trust,
1 Department of Molecular Pathology and Immunology, University College London, London, UK and
2 Department of Immunology, Free University Medical Centre, Amsterdam, The Netherlands
Abstract
Objectives. To analyse the expression of receptor activator of NF-
B (RANK) and RANK ligand (RANKL) in the joints of children with juvenile idiopathic arthritis (JIA), to characterize the phenotype of RANK+ cells and to test the hypothesis that some RANK+ cells are of the dendritic type.
Methods. Paired samples of peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) from children with oligoarticular (n=14) or polyarticular (n=4) JIA and PBMC from 10 control subjects were studied for expression of RANK, RANKL and dendritic cell-specific ICAM (intercellular adhesion molecule)-grabbing non-integrin (DC-SIGN) by the reverse transcriptase–polymerase chain reaction and three-colour flow cytometry. Expression of DC-SIGN and RANK was followed after 1 week of culture with granulocyte–macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4).
Results. mRNA for RANK was detected in both adherent cells and T cells from PBMC and SFMC of patients with JIA and in control PBMC, while mRNA for RANKL was detectable in the T-cell fraction from JIA patients but not in that from controls. By flow cytometry, a large number of RANK+ cells were detected in the joint; these cells had the phenotype HLA-DRhiCD86hi CD11c+ and expressed low levels of DC-SIGN.
Conclusions. There is increased expression of RANKL and RANK in the juvenile arthritic joint. RANK is expressed on a population of cells with features of dendritic cells. RANK/RANKL interactions may contribute to the survival of inflammatory cells within the joint, as well as to erosions and osteoporosis in juvenile arthritis.
Notes
Correspondence to: L. R. Wedderburn, Rheumatology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK. E-mail: l.wedderburn{at}ich.ucl.ac.uk
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