Glycoprotein YKL-40 Levels in Plasma Are Associated with Fibrotic Changes on HRCT in Asbestos-Exposed Subjects

Abstract

YKL-40 is a chitinase-like glycoprotein produced by alternatively activated macrophages that are associated with wound healing and fibrosis. Asbestosis is a chronic asbestos-induced lung disease, in which injury of epithelial cells and activation of alveolar macrophages lead to enhanced collagen production and fibrosis. We studied if YKL-40 is related to inflammation, fibrosis, and/or lung function in subjects exposed to asbestosis. Venous blood samples were collected from 85 men with moderate or heavy occupational asbestos exposure and from 28 healthy, age-matched controls. Levels of plasma YKL-40, CRP, IL-6, adipsin, and MMP-9 were measured with enzyme-linked immunosorbent assay (ELISA). Plasma YKL-40 levels were significantly higher in subjects with asbestosis (n = 19) than in those with no fibrotic findings in HRCT following asbestos exposure (n = 66) or in unexposed healthy controls. In asbestos-exposed subjects, plasma YKL-40 correlated negatively with lung function capacity parameters FVC (Pearson's r −0.259, p = 0.018) and FEV1 (Pearson's r −0.240, p = 0.028) and positively with CRP (Spearman's rho 0.371, p < 0.001), IL-6 (Spearman's rho 0.314, p = 0.003), adipsin (Spearman's rho 0.459, p < 0.001), and MMP-9 (Spearman's rho 0.243, p = 0.025). The present finding suggests YKL-40 as a biomarker associated with fibrosis and inflammation in asbestos-exposed subjects.

Glycoprotein YKL-40 Is Elevated and Predicts Disease Severity in Puumala Hantavirus Infection

“…This is in accordance with the perception of YKL-40 as an early inflammatory marker. This finding is also in concordance with previous studies, reporting a positive correlation of YKL-40 with IL-6 or CRP in some other inflammatory or infectious conditions [31,32,36,39,46]. In PUUV infection, on the other hand, IL-6 has predicted the outcome, but the predictive value of CRP is less clear [21].…”

“…The present study shows that plasma YKL-40 levels are elevated during acute hantavirus infection caused by PUUV. The concentrations measured during the acute illness were markedly higher than the values measured after hospitalization, which, in turn, corresponded to the YKL-40 levels of local healthy subjects in our previous studies [36,37]. To our knowledge, no previous studies have been published on YKL-40 in a hantavirus infection.…”

“…However, the complete biological function and specific receptor(s) of YKL-40 still remain unknown [31]. We have previously found YKL-40 as a contributing factor and biomarker in asthma, osteoarthritis, rheumatoid arthritis, and asbestosis, as well as a predictive factor in renal cell cancer [36,38,39,40,41].…”

Chitinase-3 like-protein-1 function and its role in diseases

“… 31 , 97 Serum CHI3L1 levels are also increased in patients with cystic fibrosis 164 as well as asbestosis. 165 …”

Chitinase-like proteins as regulators of innate immunity and tissue repair: helpful lessons for asthma?

“…Such responses likely relate to the combined effects of YKL-40 binding to and stimulating collagen fibril formation [41], in addition inhibiting collagen degradation [40]. In fact enhanced expression of YKL-40 correlates with fibrotic disorders of the lung [30,49,81] and liver [31,82]. Interestingly, YKL-40 also regulates the epithelial-mesenchymal transition (EMT) [83], a process which involves a phenotypic shift of epithelial cells towards a mesenchymal fibroblast-like cell that is highly migratory and secretes enhanced amounts of ECM proteins like collagen.…”