Clinical value of YKL‐40 in patients with polymyositis/dermatomyositis: A cross‐sectional study and a systematic review

Abstract Introduction We performed a cross‐sectional study to investigate the clinical usefulness of YKL‐40 in patients with dermatomyositis (DM) and conducted a systematic review to summarize the clinical value of YKL‐40 in patients with polymyositis (PM)/DM. Materials and methods A cross‐sectional study and a systematic review were performed to study the clinical value of YKL‐40 in patients with PM/DM. Serum YKL‐40 level was detected using enzyme‐linked immunosorbent assay, and its association with clinical and laboratory parameters was analyzed. In the systematic review, electronic databases of OVID Embase, OVID Medline, and web of science were searched to collect studies that reported clinical use of YKL‐40 in patients with PM/DM. Results In the cross‐sectional study, serum YKL‐40 level was higher in patients with DM than in healthy controls (median [interquartile range]: 84.09 [52.72–176.4] ng/ml versus 27.37 [12.30–53.58] ng/ml, p < 0.0001). Serum levels of YKL‐40 were associated with the course of DM (r = −0.469, p < 0.001), CRP (r = 0.303, p = 0.043), CK (r = 0.263, p = 0.037), and global disease activity (r = 0.628, p < 0.001). The area under the ROC curve was 0.835 (95% confidence interval 0.751–0.920). In the systematic review, a total of four studies were included with moderate to high quality. Serum level of YKL‐40 has the possibility for diagnosing PM/DM, identifying PM/DM patients with interstitial lung disease (ILD) or rapid progress ILD, and predicting death. Conclusion Serum YKL‐40 level is a possible useful biomarker for PM/DM diagnosis and may be used to predict prognosis.


| INTRODUC TI ON
Polymyositis (PM) and dermatomyositis (DM) belong to the idiopathic inflammatory myopathy group of disorders. The hallmark of PM is the presence of weakness in the proximal muscles; for DM, the clinical characteristics are rashes, such as heliotrope rash and Gottron rash, as well as muscle weakness. 1 PM/DM are associated with malignant tumors, pulmonary fibrosis, and cardiac abnormalities, which are risk factors for poor prognosis, as low as 62%. 2 Thus, early diagnosis and optimal treatment are critical to improving prognosis. The serum levels of myositis-specific antibodies play a critical role in establishing the diagnosis, predicting the prognosis, and guiding the management. [3][4][5] However, the prevalence of currently available traditional or myositisspecific autoantibodies is low, as it ranges from rare prevalence to about 50% in patients; [6][7][8] furthermore, the currently available diseasespecific autoantibodies only cover 70% of patients. 7 Therefore, novel serum biomarkers are still needed in clinical practice.
YKL-40, also named chitinase-3-like-1 protein, has a wide range of physiological functions, including participation in the regulation of cell growth and proliferation, promoting cell survival, driving the activation and differentiation of immune cells, promoting angiogenesis in cancer, and regulating inflammation.YKL-40 has also been associated with several diseases such as arthritis, diabetes, and liver fibrosis. 9 Several studies have investigated the clinical use of YKL-40 in patients with PM/DM. [10][11][12][13] Nevertheless, skin lesions are the hallmark feature of DM, and microvasculopathy plays a critical role in immune pathogenesis, which is different from the pathogenesis of PM. 14  This study had two study aims. One was to conduct a crosssectional study to assess the serum level and diagnostic value of YKL-40 in patients with DM. The other was to systematically review the clinical value of YKL-40 in patients with PM/DM. The systematic review was registered in PROSPERO (CRD42021270316) and performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. 15  Eon140423C. The quality control measurements were applied during running of all routine laboratory tests. The intra-assay % coefficient of variation (CV%) and inter-assay CV% were less than 10% and less than 12%, respectively. The results of ELISA were calculated on ELISACalc software.

| MATERIAL S AND ME
We collected blood samples from each participant at enrollment for routine laboratory tests, including serum Krebs von den Lungen activity, lung function, and laboratory tests; (5) study design was a cross-sectional study or diagnostic accuracy study. A study was excluded if it was a duplicate, a commentary, a conference abstract, or without related outcomes.
Studies selection and data extraction were performed independently by two reviews. Any disagreement on data extraction was resolved via discussion or adjudication by a third reviewer if necessary. The agency for healthcare research and quality (ARHQ) assessment tool was used to assess the methodological quality of included studies. 17

| Baseline characteristics
The characteristics of the enrolled participants are listed in Table 1 (Table 3).
Nevertheless, serum levels of YKL-40 were not associated with the pulmonary function (Table S3).

| Baseline characteristics
A total of 31 studies were found from electronic databases. After excluding irrelevant studies, four studies were included in our sys- to 62 and 53, respectively (Table 2). Overall, the quality of included studies was moderate to high (Table S1).

| Serum level of YKL-40
The systematic review reported that the detection method of serum level of YKL-40 was ELISA in all studies. The median serum level of YKL-40 in patients with PM/DM ranged from 0.54 to 84 ng/ml, which was higher than that in the controls, which varied from 0.27 to 27.8 ng/ml (Table 2).  Table 2).

| Main findings
Our study reports that the serum level of YKL-40 is significantly

| Limitations
This study has several limitations. First, serum YKL-40 was found to be an acute-phase inflammation associated biomarker, which nega-   the study, extracted the information. HYP, ZYY, TYR assessed the study quality. All authors drifted and revised the manuscript.

CO N FLI C T O F I NTE R E S T
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

DATA AVA I L A B I L I T Y S TAT E M E N T
All data are presented in tables or can be found in Appendix S1.

E TH I C A L A PPROVA L
The cross-sectional study was conducted in compliance with the Declaration of Helsinki and is approved by the ethics committee of West China Hospital (NO. 246 in 2019). Written informed consent was obtained from all participants.

S TU DY R EG I S TR ATI O N
The systematic review was registered in PROSPERO (CRD42021270316).