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Serum YKL-40 and IL-6 levels correlate with ultrasound findings of articular and periarticular involvement in patients with systemic sclerosis

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Abstract

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vascular, immune and fibrotic abnormalities in the skin and in many internal organs. New biomarkers with predictive value associated with target organ involvement are needed. The up-regulation of IL-6 production is associated with the disease activity and in the development of cardiopulmonary manifestations in SSc patients. The protein YKL-40 is a promising and intensively investigated biomarker related to inflammatory and tumor diseases. The objective of the study was to investigate how serum levels of YKL-40 and IL-6 correlate with articular and periarticular involvement in patients with SSc assessed by high-frequency ultrasonography. 59 SSc patients (56 women, 3 men) and 23 age-matched healthy subjects (21 women and 2 men) were investigated for serum YKL-40 and IL-6 (by ELISA). All the patients and healthy controls underwent clinically and high-frequency ultrasound assessment of articular and periarticular structures. Joint involvement was scored according to the new US10SSc score. Clinical data about the SSc patients showed significantly higher mRSS in the dcSSc patients (p = 0.015). Clinical synovitis was diagnosed in 16.9% of all patients: 22.5% of the dcSSc group and 10.7% of the lcSSc group (p = 0.306). On the other hand, US synovitis was detected in a higher percentage: 44% of all SSc patients; 54.8% of the dcSSc group and 32% of the lcSSc patients (p = 0.116). Clinical tenosynovitis was established in 6.7% of all patients: 9.7% of the dcSSc group and 3.5% of the lcSSc group (p = 0.614). US tenosynovitis was detected at a higher rate: 27% of all patients; 32.25% of the dcSSc group and 21.4% of the lcSSc group (p = 0.393). Serum level of YKL-40 was significantly higher in SSc patients (115.62 ng/ml ± 89.51, median 86.76) compared to the healthy controls (46.28 ng/ml ± 18.91, median 44.02), p < 0.001. IL-6 level was also significantly higher in the patient group (27.60 ± 48.80 pg/ml; median 8.32) vs. the healthy controls (5.79 ± 2.46 pg/ml, median 5.52). In the patient subgroups, YKL-40 and IL-6 levels were significantly elevated in dcSSc compared to lcSSc patients: YKL-40 dcSSc (159.52 ng/ml ± 102.81; median 136.20 ng/ml) vs. lcSSc patients (89.31 ng/ml ± 50.36; median 68.03 ng/ml;), p < 0.001; IL-6 dcSSc patients (49.64 pg/ml ± 46.37; median 16.36 pg/ml) vs. lcSSc patients (13.22 pg/ml ± 8.95; median 8.65 pg/ml), p = 0.048. A statistically significant correlation of high magnitude (rs = 0.884, p < 0.001) was observed between YKL-40 and the ultrasound 10 Systemic sclerosis score (US10SSc) and between IL-6 and the US10SSc score (rs = 0.808, p < 0.001). Serum YKL-40 and IL-6 in combination with US may have a potential role in defining disease activity and stratification, predicting organ involvement, and in the prognosis of SSc.

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Acknowledgements

The study is supported by grant from Medical University, Plovdiv (DP06/2018) and the Bulgarian Association of Musculoskeletal Ultrasound (BAMSU).

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Authors and Affiliations

  1. Department of Internal Diseases, Medical University of Plovdiv, Plovdiv, Bulgaria

    Rositsa Karalilova, Tanya Sapundzhieva, Zguro Batalov & Anastas Batalov

  2. Rheumatology Clinic, University Hospital “Kaspela”, Medical University of Plovdiv, 64 Sofia str., 4001, Plovdiv, Bulgaria

    Rositsa Karalilova, Tanya Sapundzhieva, Zguro Batalov & Anastas Batalov

  3. Department of Medical Biology, Faculty of Medicine, Medical University of Plovdiv, Plovdiv, Bulgaria

    Maria Kazakova, Valentin Dichev & Victoria Sarafian

  4. Technological Center for Emergency Medicine, Plovdiv, Bulgaria

    Valentin Dichev & Victoria Sarafian

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  1. Rositsa Karalilova
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Contributions

AB and VS contributed to the concept, design of the study and final approval of the manuscript. RK and MK contributed to manuscript writing and interpretation of the results. ZB and TS contributed to data collection, clinical examination, data analyses and final approval of the manuscript. MK, VD, VS contributed to data collection, immunological analysis, critical revision and final approval of the manuscript. All authors participated in the interpretation of the results, editing, and approved the final version of the manuscript. All co-authors are fully responsible for the integrity of the study and the final manuscript.

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Correspondence to Rositsa Karalilova.

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The study was approved by ethics committee of Medical University of Plovdiv (protocol № 3/31.05.2018). All study procedures were performed according to the ethical principles of the Declaration of Helsinki and Good Clinical Practice.

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Voluntarily signed informed consent was obtained from all participants before entering the study in accordance with the ethical recommendations of the Helsinki Declaration.

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Karalilova, R., Kazakova, M., Sapundzhieva, T. et al. Serum YKL-40 and IL-6 levels correlate with ultrasound findings of articular and periarticular involvement in patients with systemic sclerosis. Rheumatol Int 39, 1841–1848 (2019). https://doi.org/10.1007/s00296-019-04402-9

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