Longitudinal and Comparative Measures of Serum Chitotriosidase and YKL-40 in Patients With Idiopathic Pulmonary Fibrosis

Abstract

BackgroundAlthough chitin is absent in humans, chitinases are present in healthy subjects and show dysregulated expression in a variety of diseases resulting from abnormal tissue injury and repair responses. It was shown that chitotriosidase (chitinase 1/CHIT1) and structurally-related chitinase 3-like 1 protein (CHI3L1/YKL-40) play important roles in the pathobiology of idiopathic pulmonary fibrosis (IPF), however little is known about their longitudinal serum levels and relationship to clinical measures in IPF.MethodsThe present study is the first to evaluate serial measurements of serum CHIT1 activity and YKL-40 concentrations in patients with IPF starting antifibrotic treatment and followed up for 24 months. In addition, baseline serum CHIT1 and YKL-40 were compared between patients with IPF and control subjects, and possible CHIT1 and YKL-40 relationships to longitudinal clinical assessments in IPF were explored.ResultsBaseline serum CHIT1 activity and YKL-40 concentrations were significantly elevated in patients with IPF compared to control subjects and showed similar discriminatory ability in distinguishing IPF from controls. No significant differences between the median serum CHIT1 activity and YKL-40 concentration measured over a study follow-up were noted. We found significantly elevated baseline serum CHIT1 activity in the progressors compared with the stables in the first year, while significantly increased baseline serum CHIT1 activity was noted in the stables compared to the progressors in the second year. Additionally, we observed a significant negative correlation between a change in serum YKL-40 concentration and a change in forced vital capacity (FVC) % predicted (% pred.) in the stables subgroup, whereas, a change in serum CHIT1 activity correlated negatively with a change in FVC% pred. in the progressors subgroup.ConclusionsThis explorative study findings add further evidence that CHIT1 and YKL-40 are upregulated in patients with IPF, and suggest that longitudinally stable serum CHIT1 activity and YKL-40 concentration levels may potentially be associated with the antifibrotic treatment response. In addition, our findings are supporting the possible role of CHIT1 and YKL-40 as candidate diagnostic and prognostic biomarkers in IPF. Further research is needed to validate present study findings.

Molecular Pathogenesis of Fibrosis, Thrombosis and Surfactant Dysfunction in the Lungs of Severe COVID-19 Patients

“…A systematic review conducted by Tong et al showed that YKL-40 serum levels were higher in patients with interstitial lung disease (ILD), which includes PF, than in the control group [ 125 ]. Similar results were also obtained by Majewski et al in which the YKL-40 serum concentration was statistically significantly higher in patients with idiopathic pulmonary fibrosis than in healthy people [ 126 ]. Early positive results of YKL-40 protein research, obtained in various lung diseases, have become the basis for the analysis of this parameter in patients with COVID-19.…”

YKL-40 as a novel diagnostic biomarker in Toxoplasmosis

“…This assumption is based on the previously observed data about parasite development and pathogenicity, which revealed that the parasite induces acute inflammatory responses in the infected tissues and encysts in the muscular and neural tissues. On the other hand, previous studies have documented the major role of YKL-40 in the inflammatory reactions, tissue injuries, remodeling, and repair, 43,51,52 and polarization of Th2, 40,53,54 which are all from the induced changes and mechanisms during the infection and the conflict against the parasite invasion. In addition, as variety of cells, including macrophages, neutrophils, SMC and FLC, are known to secrete the YKL-40 40,41,55,56 and essentially engaged in fighting the parasite and inducing an immune response, 57,58 it has been expected that excessive secretion of…”

“…The YKL-40 has important functions in many biological processes. It plays a major role in the inflammatory reactions, tissue injury, remodeling, and repair, 43 and has a strong correlation with many diseases. 44 However, it is still unknown whether YKL-40 is markedly secreted in Toxoplasmosis or not and whether its level is different in the acute or chronic stage of the infection.…”

Evaluation of Circulating Chitotriosidase Activity in Children with Obesity

“…Syndromic obesity was defined as the presence of dysmorphic features, organ malformations, hyperphagia, or cognitive delay in obese children with or without detected mutations or chromosomal abnormalities where, in most cases, an appropriate assent was not possible [36]. Previous studies had indicated changes in the CHIT1 activity in the presence of acute infections [37][38][39][40] and chronic inflammatory diseases [41][42][43][44][45]. Children homozygotes for dup24 who presented no CHIT1 activity [27,30] were also excluded.…”