YKL-40 as a new biomarker of disease activity in Takayasu arteritis
Introduction
The YKL-40 protein, also called CHI3L1, is a mammalian member of the family of 18-glycosyl hydrolases [1,2]. YKL-40 is a heparin- and chitin-binding lectin that does not exhibit chitinase activity. YKL-40 is usually secreted from activated neutrophils and macrophages in different tissues in response to inflammation [1,3]. Recent research has demonstrated that YKL-40 is also secreted by vascular smooth muscle cells, cancer cells, as well as cancer-associated fibroblasts [2,[4], [5], [6]]. The precise biological function of YKL-40 is not clear; however, there is some indication that it is involved in the inflammation and remodelling of the extracellular matrix after tissue injury [1,2]. Recently, YKL-40 has received attention as a potential biomarker in some pathological conditions characterized by tissue injury and inflammation, such as rheumatoid arthritis and liver fibrosis [7,8]. Furthermore, elevated serum levels of YKL-40 have been positively associated with disease activity and disease severity in patients with giant cell arteritis, atherosclerosis, coronary heart disease as well as Behcet disease [[9], [10], [11], [12]]. Based on these findings, YKL-40 might be a valuable target of investigation in the context of cardiovascular disease.
Takayasu arteritis (TA) is a rare systemic vasculitis that causes stenosis, occlusion, and dilatation of large vessels such as the aorta and its major branches [13]. TA is typically characterized by a prolonged, indolent course with nonspecific manifestations such as fever, malaise, weight loss and headache/dizziness [14]. Further, important organs may gradually become dysfunctional due to stenosis or occlusion of a culprit vessel. TA tends to progress despite treatment with glucocorticoid and/or immunosuppressive agents [15,16]. Therefore, it is crucial to identify more biomarkers to monitor disease activity and possibly predict exacerbations, in order to aid early treatment.
The causes of TA are still unknown, but its prominent pathological feature is an inflammatory infiltrate composed of T lymphocytes, macrophages, as well as fibroblasts, and vascular remodelling and fibrosis in response to early vascular inflammation [17,18]. Several inflammatory cytokines including interleukin (IL)-6, IL-17 and interferon (IFN)-γ have been reported to play an important role in TA [19,20]. Our previous study confirmed the crucial role of IL-6 in the vascular fibrosis of TA, and its relationship with disease activity [19,21]. The expression of YKL-40 has been reported to be regulated by inflammatory cytokines, including IL-6 and IL-17 [1,3]. Based on these findings, it would be interesting to evaluate the serum YKL-40 level in TA and determine its association with the levels of associated cytokines such as IL-6 and IL-17. That is, the serum levels of YKL-40 may have potential as a biomarker for the assessment of disease activity in TA.
The present study evaluates the potential of YKL-40 for monitoring disease activity in TA and analyses its association with previously reported inflammatory cytokines associated with TA [[22], [23], [24]], including IL-6, IL-8, IL-17, sCD163, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, MMP-9, osteopontin (OPN), pentraxin (PTX)-3 and IFN-γ.
Section snippets
Patients
A total of 40 patients, who first visited our department between January 2017 and January 2018, were enrolled in this study. The inclusion criteria were (i) classified as TA according to the 1990 ACR classification criteria [25]; (ii) absence of other concomitant autoimmune diseases, malignancy, or infection; and (iii) 6-month follow-up. Age and sex matched healthy controls (n = 40) were also enrolled.
The study was approved by the Institutional Review Board of Zhongshan Hospital, Fudan
Patient characteristics
The study population comprised 40 patients (mean age, 31 ± 4 years; female:male ratio, 9:1; mean duration of disease, 23 ± 17 months). The active group comprised 28 patients, whereas the inactive group comprised 12 patients. The detailed demographic and clinical characteristics of the patients are summarized in Supplementary Table.
In the active group, prednisone treatment at a dosage of 0.8–1.0 mg·kg−1·day−1 (p.o.) was started. After 4 weeks, the prednisone dose was tapered gradually to a
Discussion
To our knowledge, this is the first study to demonstrate the value of YKL-40 as a new biomarker of disease activity in patients with TA.
In a study on giant cell arteritis, the serum levels of YKL-40 were found to be positively correlated to disease activity and treatment response [9]. In our investigation, the YKL-40 level was not only increased in active disease, but also related to the level of disease activity. Moreover, the serum levels of YKL-40 were still higher than the cut-off value
Funding
This work was supported by the Natural Science Foundation of China (No. 81601398; No. 81771730).
Acknowledgements
None.
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