Session Information
Title: Rheumatoid Arthritis - Clinical Aspects: Novel Biomarkers and Other Measurements of Disease Activity
Session Type: Abstract Submissions (ACR)
Background/Purpose
Inadequate endogenous glucocorticoid (GC) synthesis during inflammation has been proposed as an aetiological factor in the development of rheumatoid arthritis (RA). It has been shown that inflamed synovial tissue from patients with RA 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 was associated with the risk of developing persistent arthritis in patients first presenting with joint inflammation.
Methods
Blood and urine, were obtained from 76 patients with early arthritis (symptoms ≤ 12 weeks duration). The final diagnostic outcome was determined after 18 months clinical follow up when patients were assigned to one of the following three outcome groups. (1) Persistent inflammatory arthritis that did not fulfil 1987 ACR classification criteria for RA, n=13. (2) Persistent RA, according to 1987 ACR classification criteria, n=18. (3) Resolving inflammatory arthritis, n=24. Patients were classified as having a resolving inflammatory arthritis if they had no clinically apparent joint swelling at final follow-up, were not receiving disease modifying drugs or steroids and had not received such drugs in the previous 3 months. In addition, patients who fulfilled 1987 ACR classification criteria for RA and had a symptom duration of more than 12 weeks at initial assessment were recruited as patients with ‘established RA’, n=20. 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. Arthritis severity was assessed by ESR, CRP and DAS28.
Results
Systemic measures of 11β-HSD1 activity were significantly higher in patients with early arthritis whose disease went on to persist, and also in the subgroup of patients with persistent disease who developed RA, when compared with patients whose synovitis resolved over time (persistent RA, 1.34 (0.013) and resolving inflammatory arthritis, 0.96 (0.07), P=0.012), mean (SEM). Levels of ESR at baseline were not significantly different between the different outcome groups. However the levels of CRP in patients with early synovitis that persisted were higher than that in patients whose synovitis resolved. We observed a significant positive correlation between systemic 11β-HSD1 activity and both ESR and CRP in patients with established RA but not in any of the early arthritis patients group.
Conclusion
The present study demonstrates that patients with a new onset of synovitis whose disease subsequently resolved had significantly lower levels of systemic 11β-HSD1 activity when compared with patients whose synovitis developed into RA or other form of persistent arthritis. This observation is contrary to that predicted on the basis of previous work and raises the possibility that a high total body 11β-HSD1 activity during early arthritis may reduce the probability of disease resolution.
Disclosure:
D. Nanus,
None;
A. Filer,
None;
L. Yeo,
None;
D. Scheel-Toellner,
None;
R. Hardy,
None;
G. Lavery,
None;
P. Stewart,
None;
C. Buckley,
None;
M. Cooper,
None;
K. Raza,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/high-11b-hsd1-activity-is-associated-with-progression-to-rheumatoid-arthritis-in-patients-with-a-new-onset-of-inflammatory-arthritis/