High YKL-40 serum levels and its expression in the muscle tissues of patients with antisynthetase syndrome

Abstract

Background The protein chitinase-3-like-1 (YKL-40) is rarely analyzed in patients with myositis. Therefore, we aimed to evaluate YKL-40 serum levels; correlate them with laboratory and clinical parameters, disease status, and treatment schemes; and analyze the YKL-40 expression in the muscle tissues of patients with antisynthetase syndrome (ASSD). Methods This cross-sectional single-center study included 64 adult patients with ASSD who were age-, gender-, and ethnicity-matched to 64 healthy control individuals. Their YKL-40 serum levels were analyzed using the Enzyme-Linked Immunosorbent Assay (ELISA) kit method, while YKL-40 expression in muscle tissues was analyzed using an immunohistochemical technique. Disease status was assessed using the International Myositis Assessment and Clinical Studies Group (IMACS) set scores. Results The patients’ mean age was 44.8 ± 11.8 years, and median disease duration was 1.5 (0.0–4.0) years. These patients were predominantly female (82.8%) and Caucasian (73.4%). Most patients had stable disease. The median YKL-40 serum level was significantly higher in patients with ASSD when compared to the healthy individuals: 538.4 (363.4–853.1) pg/mL versus 270.0 (201.8–451.9) pg/mL, respectively; P < 0.001. However, YKL-40 serum levels did not correlate with any clinical, laboratory, disease status, or therapeutic parameters (P > 0.050), except tumor necrosis factor alpha (TNF-α) serum levels (Spearman’s correlation, rho = 0.382; P = 0.007). YKL-40 was highly expressed by inflammatory cells found in muscle biopsy specimens. Conclusions High YKL-40 serum levels were observed in patients with ASSD and correlated positively with TNF-α serum levels. Moreover, YKL-40 was expressed by the inflammatory cells of the muscle tissue.

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

“…Our study reported serum level of YKL-40 was associated with disease activities, including cutaneous disease activity (r = 0.509, p < 0.001), gastrointestinal disease activity (r = 0.381, p = 0.002), cardiovascular disease activity (r = 0.329, p = 0.008), and muscle disease activity (r = 0.425, p < 0.001), and was related to several laboratory indicators, such as CRP (r = 0.303, p = 0.043), CK (r = 0.263, p = 0.037), LDH (r = 0.460, p < 0.001), and HBDH (r = 0.435, p < 0.001), which were consistent with the reports reported by Gao 2019, Jiang 2019, and Hozumi et al that YKL-40 had relationships with MYOACT (r = 0.64, p < 0.01), CRP (r = 0.34, p < 0.01; r = 0.332, p = 0.001), ESR (r = 0.61, p < 0.01; r = 0.251, p = 0.011), KL-6 (r = 0.33, p < 0.01), and ferritin (r = 0.61, p < 0.01; r = 0.46, p < 0.001) [11][12][13]. However, this is not con rmed by the results reported by Carboni 2021 et al [10]. Those uncosistent results might be explained by the fact that study population was small, patients were from different study groups, and patients were with different subgroup diagnosis.…”

“…After excluding irrelevant studies, four studies were included in our systematic review, and by adding our study results, a total of 5 studies reported the clinical value of YKL‐40 in patients with PM/DM (Figure 1 ). 10 , 11 , 12 , 13 No eligible studies were included by manually checking references. The diagnostic criteria for patients was the Bohan and Peter classification criteria in all included studies, except for Carboni 2021 which used the modified ASSD criteria classification.…”

“…A total of 31 studies were found from electronic databases. After excluding irrelevant studies, 4 studies were included in our systematic review [10][11][12][13], and by adding our study results, a total of 5 studies reported the clinical value of YKL-40 in patients with PM/DM (Fig. 1).…”

“…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 in ammation.YKL-40 has also been associated with several diseases such as arthritis, diabetes, and liver brosis [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].…”

“… 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 In order to investigate the clinical usefulness of YKL‐40 in patients with DM, especially for association of serum YKL‐40 level with the severity and disease activity of skin lesions, a cross‐sectional study was performed.…”