Expression of IL-21 receptor in synovial tissue and blood of patients with rheumatoid arthritis

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.

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).

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).

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
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, 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 > Institute of Infection Immunity and Inflammation
Journal Name:Annals of the Rheumatic Diseases
Publisher:B M J Group
ISSN:0003-4967

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