Background: Rheumatoid arthritis (RA) causes chronic inflammation and alteration of articular tissue and joints. The pathogenesis of the disease remains unclear although it is known that proinflammatory cytokines play a major role in its induction.
YKL-40 is a chitinase-like glycoprotein produced by activated macrophages, neutrophils, arthritic chondrocytes and cancer cells. It has been shown that YKL-40 is implicated in tissue remodeling, angiogenesis and inflammation.
Aim: to investigate serum and synovial YKL-40 levels in relation to IL-1β, TNF-α, and IL-6 in RA patients.
Materials and methods: Serum and synovial concentrations of YKL-40, TNF-α, IL- 6, and IL-1β were determined by ELISA in 39 patients (mean age 53.18 ± 16.54 yrs) with active RA.
Results: Serum YKL-40 levels were increased in all patients. The highest levels were found in synovial fluid (P<0.01). Our study showed a strong association between serum and synovial levels of YKL-40 and serum TNF-α and IL-1 β (P<0.05).
Conclusion: This is the first study finding a significant correlation between serum TNF-α and IL-1β and YKL-40 in active RA. We suggest that these molecules together might play a dominant role in the pathogenesis and disease activity and could possibly serve as a new diagnostic constellation in rheumatoid arthritis.
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1. Kvien T. Epidemiology and burden of illness of rheumatoid arthritis. Pharmacoeconomics 2004;22:1-12.
2. Dolhain RJ, van der Heiden AN, ter Haar NT, et al. Shift toward T lymphocytes with a T helper 1 cytokine-secretion profi le in the joints of patients with rheumatoid arthritis. Arthritis Rheum 1996;39:1961-9.
3. Bläss S, Haferkamp C, Specker C, et al. Rheumatoid arthritis: autoreactive T cells recognising a novel 68k autoantigen. Ann Rheum Dis 1997;56:317-22.
4. Johansen JS, Williamson MK, Rice JS, et al. Identifi cation of proteins secreted by human osteoblastic cells in culture. J Bone Miner Res 1992;7:501-12.
5. Hakala BE, White C, Recklies AD. Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J Biol Chem 1993;268(34):25803-10.
6. Zivanović S, Rackov L, Vojvodić D, et al. Human cartilage glycoprotein 39--biomarker of joint damage in knee osteoarthritis. Int Orthop 2009;33:1165-70.
7. Connor J, Dodds R, Emery J, et al. Human cartilage glycoprotein 39 (HC gp-39) mRNA expression in adult and fetal chondrocytes, osteoblasts and osteocytes by in-situ hybridization. Osteoarthritis Cartilage 2000;8:87-95.
8. Johansen JS. Studies on serum YKL-40 as a biomarker in diseases with infl ammation, tissue remodelling, fi broses and cancer. Dan Med Bull 2006;53:172-209.
9. Kim S, Das K, Noreen S, et al. Prognostic implications of immunohistochemically detected YKL-40 expression in breast cancer. World J Surg Oncol 2007;5:17.
10. Takahashi M, Naito K, Abe M, et al. Relationship between radiographic grading of osteoarthritis and the biochemical markers for arthritis in knee osteoarthritis. Arthritis Res Ther 2004;6:208-12.
11. Kazakova M, Batalov A, Deneva T, et al. Relationship between sonographic parameters and YKL-40 levels in rheumatoid arthritis. Rheumatol Int 2013;33:341-6.
12. Astry B, Harberts E, Moudgil K. A cytokinecentric view of the patho`genesis and treatment of autoimmune arthritis. J Interferon Cytokine Res 2011;31:927-40.
13. Clavel G, Thiolat A, Boissier M. Interleukin newcomers creating new numbers in rheumatology: IL-34 to IL-38. Jt Bone Spine 2013;80:449-53.
14. Leng R, Pan H, Tao J, et al. IL-19, IL-20 and IL-24: potential therapeutic targets for autoimmune diseases. Expert Opin Ther Targets 2011;15:119-26.
15. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classifi cation of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.
16. Goranov S, Goranova-Marinova V. Serum levels of IL-6 OPG and rankl in patients newly diagnosed for bone impairment, kidney failure and multiple myeloma. Suvremenna Medicina 2009;60:16-22. [Bulgarian]
17. Schultz N, Johansen JS. YKL-40 - a protein in the fi eld of translational medicine: a role as a biomarker in cancer patients? Cancers (Basel) 2010;1453-91.
18. Nishikawa KC, Millis AJ. gp38k (CHI3L1) is a novel adhesion and migration factor for vascular cells. Exp Cell Res 2003;287:79-87.
19. Van der Heijde DMFM, van ‘t Hof MA, van Riel PL, et al. Judging disease activity in clinical practice in rheumatoid arthritis: fi rst step in the development of a disease activity score. Ann Rheum Dis 1990;49:916-20.
20. de Rooy DP, van der Linden MP, Knevel R, et al. Predicting arthritis outcomes - what can be learned from the Leiden Early Arthritis Clinic? Rheumatology 2011;50:93-100.
21. Hambardzumyan K, Bolce R, Saevarsdottir S, et al. Pretreatment multi-biomarker disease activity score and radiographic progression in early RA: results from the SWEFOT trial. Ann Rheum Dis 2015;74(6):1102-9.
22. Arleevskaya M, Gabdoulkhakova A, Filina J, et al. Mononuclear phagocytes in rheumatoid arthritis patients and their relatives - family similarity. Open Rheumatol J 2011;5:36-44.
23. Shivaprasad H, Venkatesha, Dudics S, et al. Cytokinemodulating strategies and newer cytokine targets for arthritis therapy. Int J Mol Sci 2015;16:887-906.
24. Shu Z, Shi X, Nie D, et al. Low-Molecular-weight fucoidan inhibits the viability and invasiveness and triggers apoptosis in IL-1β-treated human rheumatoid arthritis fi broblast synoviocytes. Infl ammation 2015;38(5):1777-86.
25. Mohammadi E, Vatanpour H, Shirazi F. Immunomodulatory effects of bee venom in human synovial fi broblast cell line. IJPR 2015;14:313-20.
26. Scheller J, Chalaris A, Schmidt-Arras D, et al. The pro- and anti-infl ammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 2011;1813:878-88.
27. Lorenz H, Richter W. Osteoarthritis: cellular and molecular changes in degenerating cartilage. Prog Histochem Cyto 2006;40:135-63.