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FRI0045 Expression of IL-17A, IL-17F and their receptors in inflammatory arthritis: IL-17A expression in synovium and skin is differentially regulated by adalimumab
  1. L.G. van Baarsen1,
  2. M.C. Lebre1,
  3. D. van der Coelen1,
  4. S. Aarrass1,
  5. T.H. Ramwadhdoebe1,
  6. M.B. Teunissen2,
  7. A.W. van Kuijk1,
  8. D.M. Gerlag1,
  9. P.P. Tak1
  1. 1Clinical Immunology & Rheumatology
  2. 2Dermatology, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands

Abstract

Background Accumulating evidence suggests an important role for interleukin (IL)-17 in the pathogenesis of several inflammatory diseases, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis. IL-17A has been well studied in models of arthritis, but little is known about the relative expression and cellular source(s) of IL-17A, IL-17F, and their receptors in human synovial tissue and psoriatic skin.

Objectives To determine the origin and expression of IL-17A, IL-17F and their receptors IL-17RA and IL-17RC in synovium and skin of patients with arthritis and their change upon anti-TNF treatment.

Methods Synovial biopsies were obtained from patients with RA (n=13), PsA (n=15) and inflammatory osteoarthritis (OA, n=14). In addition, paired synovial and skin (paired lesional and non-lesional skin) samples from adalimumab treated PsA patients (n=12) were obtained before and 4 weeks after treatment. For comparison synovium (n=7) and skin (n=14) from non-inflammatory controls were included. Frozen sections were stained for IL-17A, IL-17F, IL-17RA and IL-17RC, and evaluated by digital image analysis. To determine which cells in the synovium produce IL-17A and IL-17F, double staining with CD4, CD8, CD15, CD68, CD163, CD19, CD31, Von Willebrand Factor, PNAd, Lyve-1 and tryptase was performed and evaluated by confocal microscopy.

Results Levels of IL-17A, IL-17F, IL-17RA and IL-17RC were abundantly present in synovial tissues of all patient groups and highly variable between patients. Whereas IL-17RA was mostly present in the synovial sublining, IL-17RC was abundantly expressed in the intimal lining layer. Digital image analysis showed a significant increase of only IL-17A in arthritis patients compared to non-inflamed control tissues. The expression of IL-17A, IL-17F and IL-17RA was similar in the different patient groups, while expression of IL-17RC in the intimal lining layer was significantly increased in PsA compared to OA patients. CD4 and CD8 positive cells co-stained with IL-17A and to a lesser extent with IL-17F. IL-17A and IL-17F were not expressed by CD15 en CD19 positive cells. Mast cells occasionally were positive for IL-17A/IL-17F. Interestingly, IL-17A and IL-17F staining was also observed in some macrophages as well as in endothelial cells and lymphatics. Strikingly, PsA patients treated with anti-TNF showed a significant upregulation of synovial IL-17A. In both lesional and non-lesional psoriatic skin, IL-17A and IL-17RC were abundantly present in the epidermis. Anti-TNF treatment had no effect on IL-17A and IL-17RC expression in psoriatic skin.

Conclusions Increased expression of IL-17A is not restricted to synovial tissues of RA and PsA patients but also observed in inflammatory OA. In inflamed synovium various cell types contribute to the production of IL-17A and IL-17F. Regulation of IL-17A by anti-TNF is dependent on the local tissue environment.

Disclosure of Interest None Declared

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