Article Text

PDF
SAT0003 The IL-20 Receptor Axis in Early Rheumatoid Arthritis: Novel Inflammation-Independent Links Between Rheumatoid Arthritis-Associated Autoantibodies and Radiographic Progression
  1. T.W. Kragstrup1,2,3,
  2. S.R. Greisen2,
  3. M.A. Nielsen2,
  4. C. Rhodes3,
  5. K. Stengaard-Pedersen1,
  6. M.L. Hetland4,5,
  7. K. Hørslev-Petersen6,
  8. P. Junker6,
  9. M. Østergaard4,
  10. M. Hvid2,
  11. T. Vorup-Jensen2,
  12. W. Robinson3,
  13. J. Sokolove3,
  14. B. Deleuran1,2
  1. 1Department of Rheumatology, Aarhus University Hospital
  2. 2Department of Biomedicine, Aarhus University, Aarhus, Denmark
  3. 3Stanford University, Stanford, United States
  4. 4Glostrup Hospital
  5. 5Rigshospitalet, Copenhagen
  6. 6University of Southern Denmark, Odense, Denmark

Abstract

Background Rheumatoid arthritis (RA) is characterized by high occurrence of rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and bone erosions. Successful treatment with biologic drugs such as anti-tumor necrosis factor alpha compromises the normal immune response increasing the risk of infections. The interleukin 20 receptor (IL-20R) axis comprising IL-19, IL-20, and IL-24 (“the IL-20R cytokines”) and their shared receptors IL-20R2/IL-20R1 and IL-20R2/IL-22R activates tissue homeostasis processes but not the immune system (Figure 1).

Objectives The objective of this study was to determine the role of the IL-20R axis in early RA (eRA) with focus on associations of the three cytokines with clinical disease activity and prognosis.

Methods The IL-20R cytokines were measured in plasma samples from treatment naïve early RA patients during 24 months of treatment with methotrexate, adalimumab/placebo and intra-articular glucocorticoid injections (the OPERA trial) (n=152)1. The IL-20R1 and IL-22R expression was studied in paired peripheral blood and synovial fluid cells from a different cohort of RA patients (n=15) with at least one swollen joint (for obtaining synovial fluid) by flow cytometry and confocal microscopy. Heat aggregated human gamma globulins (HAGGs) and immune complexes containing citrullinated fibrinogen (cFb-ICs) were used to stimulate myeloid cells. Osteoclasts (OCs) derived from synovial fluid cells were used to assess the effect of the IL-20R cytokines.

Results The plasma concentrations of IL-20 and IL-24 (but not IL-19) were increased in eRA patients compared with HCs (both P<0.002) and decreased after 6 months of treatment (both P<0.0001). The expression of IL-22R (but not IL-20R1) was increased on monocytes from RA synovial fluid compared with RA and HC peripheral blood. The plasma concentrations of IL-20 and IL-24 were increased in RF and ACPA positive compared with negative eRA patients (all P<0.0001). HAGGs and cFb-ICs stimulated the production of the IL-20R cytokines by myeloid cells. Increased baseline plasma concentrations of IL-20 and IL-24 associated with radiographic progression (evaluated by the total Sharp-van der Heijde score) after 12 months (Spearman's rho=0.27 and 0.23, both P<0.005) and 24 months (Spearman's rho=0.19 and 0.26, both P<0.05) in the eRA patients. No associations were observed between concentrations of the IL-20R cytokines and disease activity. The IL-22R was expressed by RANK+ OC precursors and in multinucleated TRAP+ OCs and these cells were activated by IL-20 and IL-24.

Conclusions Inflammation-independent associations of the IL-20R axis with RA-associated autoantibodies and radiographic progression in eRA were detected. Our data support that dual inhibition of IL-20 and IL-24 or attenuation of the shared IL-22R subunit could attenuate radiographic progression without compromising the normal immune response especially in seropositive RA.

References

  1. Hørslev-Petersen et al. Ann Rheum Dis. 2013.

Disclosure of Interest None declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.