SFEBES2014 Poster Presentations Steroids (39 abstracts)
High 11β-HSD1 activity is associated with progression to rheumatoid arthritis in patients first presenting with inflammatory arthritis
Dominika Nanus 1, , Andrew D Filer 1, , Lorraine Yeo 1 , Dagmar Scheel-Toellner 1 , Rowan Hardy 2 , Gareth L Lavery 2 , Paul M Stewart 5 , Christopher D Buckley 1, , Mark S Cooper 6 & Karim Raza 1,
1Rheumathology Research Group, University of Birmingham, Birmingham, UK; 2Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK; 3Rheumathology, University Hospital Birmingham NHS Foundation Trust, Birmmingham, UK; 4Rheumathology, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK; 5University of Leeds, Leeds, UK; 6ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Sydney, New South Wales, Australia.
Variation in endogenous glucocorticoid (GC) activity during inflammation has been linked to susceptibility to developing rheumatoid arthritis (RA). It has been shown that in patients with RA inflamed synovial tissue can generate active GCs through the expression of the 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), which converts cortisone to cortisol. We examined whether the total body activity of 11β-HSD1 or its expression within synovium was associated with the risk of developing persistent arthritis in patients first presenting with joint inflammation. Blood, urine, and synovial tissue biopsies were obtained from 76 patients at first presentation with arthritis. Total body 11β-HSD1 activity was determined by urinary gas chromatography/mass spectrometry and calculated as the tetrahydrocortisol+allotetrahydrocortisol/tetrahydrocortisone ((THF+alloTHF)/THE) and the cortols:cortolones ratios. Urinary 11β-HSD2 activity was measured as the UFF:UFE ratio. Synovial tissue expression of 11β-HSD1 and 11β-HSD2 was assessed by qPCR. Arthritis severity was assessed by ESR, CRP, and DAS28. Total body 11β-HSD1 activity was significantly lower in patients with arthritis that subsequently resolved than in patients with arthritis that went on to develop into persistent arthritis (Persistent RA, 1.34 (0.013) and Resolvers, 0.96 (0.07), P=0.012). Similar changes were seen in the cortols:cortolones ratio (P=0.0002). There was no difference in renal 11β-HSD2 activity between patients who resolved and those that developed persistent arthritis. Despite the difference in total body 11β-HSD1 activity there was no significant difference between groups in synovial tissue 11β-HSD1 expression. There was no difference in ESR or DAS28 between patients that resolved or went on to persistence although resolvers had a lower level of CRP. These studies demonstrate that a high total body 11β-HSD1 activity during early arthritis is associated with a reduced probability of resolution. The excess 11β-HSD1 may have an articular and/or extra-articular origin. This work raises the possibility that targeting 11β-HSD1 activity in early arthritis could impact on the development of RA.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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