Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
IL-17A Expression Is Upregulated in the Hypoxic Joint and Correlates with IL-6 Production, Inflammatory Cell Infiltrate and Oxidative Damage
Moran1, Ellen Margaret, Ng1, Chin Teck, McCormick1, Jennifer, Heydrich2, Rene, Appel2, Heiner, Fearon1, Ursula, Veale1, Douglas
IL-17A is overexpressed in the human RA joint and has been implicated in the pathogenesis of RA. The aim of this study was to examine localised expression of IL-17A in the joint and to examine its relationship to inflammatory markers and synovial tissue oxygen tension.
19 patients with inflammatory arthritis underwent needle arthroscopy. Paired serum/synovial fluid and synovial tissue were obtained. Oxygen levels in synovial tissue (tpO2) were assessed in vivo using a combined oxygen/temperature LICOX probe at the baseline prior to biologic therapy. IL-17A, CD3, CD68 and HNE (lipid peroxidation) expression was assessed by immunohistochemistry in synovial tissue sections. Dual immunofluorescence staining was carried out to co-localise IL-17A to mast cells using mast cell tryptase. IL-17A and IL-6 levels were measured by ELISA/MSD assay in the paired serum/synovial fluids (SF).Dual immunofluorescence staining was carried out to co-localise IL-17A to mast cells using mast cell tryptase.
Dual immunoflourescent staining demonstrated co-localisation of IL-17A expression to mononuclear cells and mast cells in the sublining. The number of IL-17A producing mononuclear cells correlated with IL-17 serum levels (r2=.545, p<0.05). The number of IL-17-secreting mast cells was found to correlate with sublining CD68 expression (r2=.618) and expression of lipid peroxidation (HNE) staining (r2=.570) (p<0.05). IL-17A SF levels correlated with serum and SF IL-6 expression (p<0.05). SF levels also correlated with CD3 expression in the sublining (r2=.430, p<0.05) and lining layer (r2=.545, p<0.05) of synovial tissue. The median tpO2 level in the synovial tissue was profoundly hypoxic 3.2% (range 0.457.7%) and inversely correlated with synovial tissue expression of CD68 and CD3 (r2=-.615, p<0.001 and r2-.611, p<0.01 respectively). When patents were categorized into tp02 <>20mmHg there was no significant difference in tissue or SF levels of IL-17A, however serum levels of both IL-17A and IL-6 were significantly higher in patients with a tp02 <20mmHg (p<0.05) suggesting a systemic effect on these cytokines by hypoxia.
In this study we demonstrate localisation of IL-17A expression to mononuclear cells and mast cells, levels of which correlated with markers of tissue inflammation and damage in the joint. We demonstrated low tpO2 levels in the joint are inversely related to tissue inflammatory markers. Serum IL-17A levels were inversely related to tpO2 levels, however had no association with tissue and SF IL-17A levels, suggesting a divergence in mechanisms regulating IL-17A systemically and locally in the joint.
To cite this abstract, please use the following information:
Moran, Ellen Margaret, Ng, Chin Teck, McCormick, Jennifer, Heydrich, Rene, Appel, Heiner, Fearon, Ursula, et al; IL-17A Expression Is Upregulated in the Hypoxic Joint and Correlates with IL-6 Production, Inflammatory Cell Infiltrate and Oxidative Damage [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1343