Comparative significance of YKL-40 in different types of arthritis
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1
Medical University - Plovdiv, Medical Biology, Bulgaria
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2
Medical University - Plovdiv, Department of Rheumatology, Bulgaria
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3
Medical University - Plovdiv, Department of Medical Informatics, Biostatistics and e-learning, Bulgaria
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4
Medical University - Sofia, Clinic of Rheumatology, Bulgaria
BACKGROUND: The YKL-40 glycoprotein is considered as а novel biomarker of disease activity and poor prognosis in patients with disorders characterized by inflammation and tissue remodeling (1). The complete biological function of the YKL-40 protein is still unknown. Serum YKL-40 as a potential biomarker for the risk of progression of joint damage in patients with rheumatoid arthritis is discussed. Some authors regard it as a serious parameter in disease diagnosis and monitoring (2,3), others disregard its importance in disease activity (4). Few information has been obtained about serum and synovial YKL-40 levels in rheumatoid, psoriatic and gout arthritis.
The aim of the study is to evaluate serum and synovial YKL-40 levels in these diseases and its association with proinflammatory cytokines such as TNF-α and IL-6.
MATERIAL AND METHODS: The investigation involved 101 patients with active inflammatory arthropathy – 39 with rheumatoid arthritis (aged 53.18 ± 2.29), 14 – with psoriatic arthritis (aged 49.36 ± 4.67), 8 patients with gout arthritis (aged 54.50 ± 5.32). The patients with rheumatoid and psoriatic arthritis were treated with slow-acting antirheumatic (DMARDS) and nonsteroidal anti-inflammatory (NSAIDS) drugs. Gout arthritis patients were treated with NSAIDS only. The control group consisted of 40 age-matched healthy individuals.
The serum and synovial concentrations of YKL-40, TNF-α and IL-6 were determined by ELISA method, using commercial kits (Quidel, San Diego, CA; Biolegend, Genaxxon) according to the manufacturers’ instructions. All samples were analyzed in duplicates. Statistical analysis was carried out with the SPSS v 17.0 statistical software. All P-values were two-tailed.
RESULTS AND DISCUSSION: In all patients with arthritis, the concentration of serum YKL-40 was remarkably elevated compared to the serum level in the control group. The synovial level of the protein was significantly higher in comparison with the serum value (P ≤ 0.01). The synovial fluid levels of proinflammatory cytokines in patients with arthritis were higher compared to the serum level. In our study, a strong association between serum and synovial levels of YKL-40 and serum TNF-α in patients with rheumatoid arthritis (P ≤ 0.01) was detected and absence of relationship with serum IL-6. The circulating monocytes are the main source of serum TNF-α and this cytokine is involved in the pathogenesis of rheumatoid arthritis and serves as a target for the therapeutic treatment (5). It is shown that TNF-α could induce secretion of YKL-40 by chondrocytes (1). We hypothesized that YKL-40 could provide specific view of the local inflammation process. Several studies reveal that this glycoprotein participates in cell differentiation, tissue remodeling, angiogenesis and inflammation (8). In patients with psoriatic and gout arthritis, no evidence of correlation between levels of YKL-40 and proinflammatory cytokines was observed. The pathogenesis of psoriatic and gout arthritis is still incompletely revealed. The pathophysiological role of synovium and the regulation of cytokine biosynthesis are just beginning to be elucidated (6). The extremely high serum and synovial levels of YKL-40 in gout patients might be due to the acute inflammation induced by monosodium urate crystals (7). Our previous investigations demonstrate that increased YKL-40 levels are associated with inflammation in rheumatoid arthritis. A strong correlation between serum YKL-40 concentration and conventional markers of biochemical assessment of disease activity such as ESR (r = 0.446, P = 0.003) and CRP (r = 0.582, P = 0.004) is determined (9). Our data suggest potential involvement of YKL-40 in inflammation and disease activity in rheumatoid arthritis.
CONCLUSION: In conclusion, the significant correlation between serum TNF-α and YKL-40 in rheumatoid arthritis suggests that these markers might play a dominant role in the pathogenesis and disease activity. The different concentration of YKL-40 in the three types of arthritis studied might reflect different pathogenetic routes in these inflammatory joint diseases.
Acknowledgements
The study is supported by grant ДП – 08/2012 from Medical University– Plovdiv and partially by grant DUNK-01-2/2009 from the Ministry of Education and Science.
References
1. Dan Med Bull 2006; 53:172-209; 2. Int Orthop 2009; 33:1165–1170; 3. Arthritis Res Ther 2004; 6:208-212; 4. Ann Rheum Dis 2009; 69:345-351 doi:10.1136/ard.2009.113092; 5. The Open Rheumatology Journal 2011; 5:36-44; 6. Autoimmunity Reviews 2012; dx.doi.org/10.1016/j.autrev.2012.10.002; 7. Gout Lancet 2010; 375:318-328; 8. Cell. Signal. 2013, dx.doi.org/10.1016/j.cellsig.2013.03.016; 9. Rheumatol Int. 2012, DOI: 10.1007/s00296-012-2387-3.
Keywords:
YKL-40,
Arthritis,
biomarker,
Cytokines,
Inflammation
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Kazakova
M,
Batalov
A,
Mateva
N,
Kolarov
Z and
Sarafian
V
(2013). Comparative significance of YKL-40 in different types of arthritis.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00744
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Received:
13 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Prof. Victoria Sarafian, Medical University - Plovdiv, Medical Biology, Plovdiv, Bulgaria, sarafian@abv.bg