Serum soluble interleukin 7 receptor is strongly associated with lupus nephritis in patients with systemic lupus erythematosus
- Valérie Badot1,2,
- Remco K M A C Luijten3,
- Joel A van Roon3,
- Geneviève Depresseux1,
- Selda Aydin4,
- Benoît J Van den Eynde5,
- Frédéric A Houssiau1,
- Bernard R Lauwerys1
- 1Pôle de Recherche en Rhumatologie, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels, Belgium
- 2Department of Rheumatology, Centre Hospitalier Universitaire-Brugmann, Brussels, Belgium
- 3Department of Rheumatology and Clinical Immunology, UMC Utrecht, Utrecht, The Netherlands
- 4Department of Pathology, Université catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels, Belgium
- 5Ludwig Institute for Cancer Research, Brussels Branch & de Duve Institute, Université catholique de Louvain, Brussels, Belgium
- Correspondence to Dr B R Lauwerys, Pôle de Recherche en Rhumatologie, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain and Cliniques Universistaires Saint-Luc, Avenue Hippocrate 10, boîte B2.5390, Brussel 1200, Belgium;
- Received 16 July 2012
- Revised 11 November 2012
- Accepted 2 December 2012
- Published Online First 22 December 2012
Background The soluble form of the interleukin 7 receptor (sIL-7R) is produced by fibroblasts after stimulation with proinflammatory cytokines. Increased sIL-7R serum and synovial fluid levels were recently demonstrated in patients with rheumatoid arthritis.
Objectives To investigate whether sIL-7R production is dysregulated in systemic lupus erythematosus (SLE), and whether this correlates with disease activity.
Methods Serum and urine sIL-7R concentrations were measured by ELISA, and sIL-7R quantitative PCR (qPCR) studies were performed in peripheral blood mononuclear cells (PBMCs). IL-7R, tumour necrosis factor α (TNFα), IL-1β and IL-17 immunostainings were performed on kidney sections.
Results sIL-7R concentrations were significantly higher in SLE sera than in controls, and correlated with SLE Disease Activity Index (SLEDAI) scores. Accordingly, serum sIL-7R levels were strongly raised in patients with nephritis. Moreover in patients with lupus nephritis, serum sIL-7R decreased upon treatment. sIL-7R gene expression in PBMCs was similar in patients with lupus nephritis and controls. By contrast, abundant perivascular IL-7R expression was seen in SLE kidney biopsy specimens, which was associated with expression of TNFα in the surrounding tissue.
Conclusions Our data indicate that sIL-7R is a marker of SLE disease activity, especially nephritis. In contrast to conventional disease activity markers, sIL-7R is not produced by immune cells, but might instead reflect activation of tissue cells in the target organ.
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