Frleta, M., King, V., Reilly, J.H., Gilchrist, D.S., Tornehave, D., Lundsgaard, D., Miller, A.M. and McInnes, I.B. (2012) Expression of IL-21 receptor in synovial tissue and blood of patients with rheumatoid arthritis. Annals of the Rheumatic Diseases, 71(Sup. 1), A83. (doi: 10.1136/annrheumdis-2011-201238.25)
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Abstract
Background and objectives: Cytokines regulate a broad range of inflammatory pathways in the pathogenesis of Rheumatoid Arthritis (RA), and cytokine blockade against tumour necrosis factor α and IL-6 has offered substantial advances in the treatment of articular inflammation. However, a large proportion of patients will not respond or exhibit only a partial response to treatment and new therapies are thus required. IL-21 is a member of the four-α-helix bundle family of cytokines that mediates pleiotropic effects through the IL-21 receptor (IL-21R). Since potency of IL-21 is mainly dependent on presence and abundance of its receptor on different cells types, the objective of this study was to characterise expression of IL-21R in the synovium and blood of patients with RA. <p/>Materials and methods: Immunohistochemistry for IL-21R was carried out on synovial tissue samples derived by arthroplasty from patients with RA (n=5) obtained from the Institute of Infection, Immunity and Inflammation Research Tissue Bank. Mononuclear cells were separated out from peripheral blood (PBMC) of 10 RA patients or 3 healthy controls on a density gradient using Histopaque (Sigma) and analysed by flow cytometry for IL-21R expression on T cells (CD3/CD4/CD8), B cells (CD19/CD27) and NK cells (CD16/CD56). <p/>Results: Expression of IL-21R was detected in 5/5 synovial RA tissues. The IL-21R+ cells were located in the synovial intimal and sublining layers and in lymphoid aggregates. Flow cytometric analysis on blood PBMC revealed that IL-21R is highly expressed on both CD4+ (73.04%, 12.58 MFI) and CD8+ (50.88%, 13.69 MFI) T cells, as well as on a proportion of NK cells (73.83%, 19.15 MFI) in RA patients. On B cells, IL-21R expression was higher on the CD27- fraction of naïve B cells (95.19%, 37.02 MFI), with lower expression on the CD27+ memory B cells (15.2%, 32.22 MFI). <p/>Conclusions: Our results show increased expression of IL-21R in established RA synovial tissue and peripheral blood, and indicate that targeting of the IL-21/IL-21R pathway may be a valid therapeutic strategy for the treatment of RA.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | McInnes, Professor Iain and Reilly, Mr James and Gilchrist, Dr Derek and Miller, Dr Ashley and King, Dr Vicky and Frleta-Gilchrist, Dr Marina |
Authors: | Frleta, M., King, V., Reilly, J.H., Gilchrist, D.S., Tornehave, D., Lundsgaard, D., Miller, A.M., and McInnes, I.B. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Annals of the Rheumatic Diseases |
Publisher: | B M J Group |
ISSN: | 0003-4967 |
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