AB0098
A UNIQUE SUBSET OF RHEUMATOID ARTHRITIS DEFINED BY A DISTINCT SERUM CYTOKINE PROFILE
M. H. Al-Mossawi 1,*M. Roy 1L. Clarke 1S. Webber 2S. Zakout 1R. H. Straub 3M. Perry 4M. Lee 4J. R. Kirwan 1R. Winfield 4
1Academic Rheumatology Department, University Hospitals of Bristol, Bristol, 2Rheumatology Department, Weston General Hospital, Weston, United Kingdom, 3Dept. of Internal Medicine, Lab of Exp. Rheumatology & Neuroendocrine Immunology, Regensburg, Germany, 4Rheumatology Department, Plymouth Hospitals NHS Trust, Plymouth, United Kingdom
Background: Research into the pathogenesis of rheumatoid arthritis (RA) has been focusing on identifying disease biomarkers that can predict response to therapy. Early work identified differing levels of pro-inflammatory cytokines within a cohort of RA patients [1]. A recent study looking at the role of a modified release glucocorticoid preparation in the management of RA may have identified a distinct subgroup of patients who are resistant to therapy [2] with raised circulating levels of the cytokines TNF-α, IL-4, IL-1 receptor antagonist (IL-1ra) and IL-1β compared to treatment responders. The concept of glucocorticoid resistance in RA has been observed in other studies and across the spectrum of inflammatory disorders [3,4].
Objectives: This study explores the the possibility of identifying a treatment resistant phenotype subset of patients with RA through peripheral serum cytokine measurements.
Methods: 41 patients with RA were recruited from general rheumatology clinics in the South-West of the United Kingdom (Bristol and Plymouth). Additional exclusion criteria included active malignancy, active infection and co-existing auto-immune disease. Patient blood samples were taken in the morning to minimise diurnal cytokine variations and cytokine assays were performed using a MILLIPLEX® MAP multiplex assay kit at a commercial laboratory in Germany.
Results: Results were analysed according to the number of patients who had raised serum TNF-α, IL-4, IL-1ra and IL-1β above the cohort median for each cytokine. The frequencies of the number of patients who had 0,1,2,3 or all 4 cytokines raised were recorded.This revealed a biphasic distribution of patients with 16/41 patients having 3 or 4 raised cytokines versus 22/41 patients having only 1 or 0 cytokines raised. Only 3 patients had 2 raised cytokines. This is a much smaller figure than predicted, as we would expect the population to be normally distributed. The P value for the Chi squared test comparing the observed population versus the expected normal distribution was <0.0001.
Conclusions: These results confirm previous observations that a distinct subset of patients with rheumatoid arthritis patients can be identified through the serum cytokine signature. Previous studies seem to imply that these patients may exhibit a glucocorticoid resistant phenotype. Further work is planned to explore the association of these two subsets of rheumatoid arthritis with various clinical characteristics.
References: [1]Ulfgren AK, et al. Interindividual and intra-articular variation of proinflammatory cytokines in patients with rheumatoid arthritis: potential implications for treatment. Ann Rheum Dis 2000;59(6):439-47. [2]Clarke LL et al. Alleviation of morning joint stiffness by low-dose prednisone in rheumatoid arthritis is associated with circadian changes in IL-6 and cortisol. International Journal of Clinical Rheumatology 2011; 6(3):273-279 doi 10.2217/ijr.11.12 [3]Sliwinska-Stanczyk P et al. The effect of methylprednisolone on the proliferation of PBMCs obtained from steroid-sensitive and steroid-resistant rheumatoid arthritis patients. Scandinavian Journal of Rheumatology. 2007;36:167-71. [4]Barnes, P.J. & Adcock, I.M. Glucocorticoid resistance in inflammatory diseases. The Lancet 2009; 373:1905–1917
Disclosure of Interest: None Declared