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Chitinase-like protein YKL-40 correlates with inflammatory phenotypes, anti-asthma responsiveness and future exacerbations.

ABSTRACT: BACKGROUND:Asthma is a heterogeneous chronic airway disease, which may be classified into different phenotypes. YKL-40 is a chitin-binding glycoprotein with unclear functions, but its expression is associated with inflammation and tissue remodeling. However, few studies have explored whether YKL-40 is associated with inflammatory phenotypes of asthma. METHODS:The study had two parts. Study I (n?=?115) was a one-year prospective cohort designed to explore the relationship of serum YKL-40 levels with inflammatory phenotypes of asthma at baseline, and during exacerbations. Study II (n?=?62) was a four-week prospective cohort designed to define whether serum YKL-40 levels could predict responses to a fixed anti-asthma regimen. YKL-40, IL-6 and CCL22 levels were detected using ELISA, and a sputum inflammatory panel (including IL-1?, IL-5, IL-8 and TNF-?) was assessed using Luminex-based MILLIPLEX assay. RESULTS:Study I: Serum YKL-40 levels in non-eosinophilic asthma (NEA) i.e. neutrophilic (47.77 [29.59, 74.97] ng/mL, n?=?40) and paucigranulocytic (47.36 [28.81, 61.68] ng/mL, n?=?31) were significantly elevated compared with eosinophilic asthma (31.05 [22.41, 51.10] ng/mL, n?=?44) (P?=?0.015). Serum YKL-40levels positively correlated with blood neutrophils, sputum IL-1? and plasma IL-6 but negatively correlated with serum IgE and blood eosinophils (all P???0.05). Baseline YKL-40 levels predicted moderate to severe exacerbations within a one-year period (aOR?=?4.13, 95% CI?=?[1.08, 15.83]). Study II: Serum YKL-40 was an independent biomarker of negative responses to anti-asthma regimens (adjusted Odds Ratio [aOR]?=?0.82, 95% CI?=?[0.71, 0.96]. CONCLUSIONS:These studies show that YKL-40 is a non-type 2 inflammatory signature for NEA, which could predict responsiveness or insensitivity to anti-asthma medications and more exacerbations. Further studies are needed to assess whether monitoring YKL-40 levels could provide potential implications for clinical relevance.

SUBMITTER: Liu L

PROVIDER: S-EPMC6530174 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Chitinase-like protein YKL-40 correlates with inflammatory phenotypes, anti-asthma responsiveness and future exacerbations.

Liu Lei L Zhang Xin X Liu Ying Y Zhang Li L Zheng Jing J Wang Ji J Hansbro Philip M PM Wang Lei L Wang Gang G Hsu Alan Chen-Yu AC

Respiratory research 20190522 1

<h4>Background</h4>Asthma is a heterogeneous chronic airway disease, which may be classified into different phenotypes. YKL-40 is a chitin-binding glycoprotein with unclear functions, but its expression is associated with inflammation and tissue remodeling. However, few studies have explored whether YKL-40 is associated with inflammatory phenotypes of asthma.<h4>Methods</h4>The study had two parts. Study I (n = 115) was a one-year prospective cohort designed to explore the relationship of serum ...[more]

PMID: 31113430

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Project description:Alzheimer's disease (AD) pathology appears several years before clinical symptoms, so identifying ways to detect individuals in the preclinical stage is imperative. The cerebrospinal fluid (CSF) Tau/A?42 ratio is currently the best known predictor of AD status and cognitive decline, and the ratio of CSF levels of chitinase-3-like 1 protein (CHI3L1, YKL-40) and amyloid beta (A?42) were reported as predictive, but individual variability and group overlap inhibits their utility for individual diagnosis making it necessary to find ways to improve sensitivity of these biomarkers.We used linear regression to identify genetic loci associated with CSF YKL-40 levels in 379 individuals (80 cognitively impaired and 299 cognitively normal) from the Charles F and Joanne Knight Alzheimer's Disease Research Center. We tested correlations between YKL-40 and CSF Tau/A?42 ratio, A?42, tau, and phosphorylated tau (ptau181). We used studentized residuals from a linear regression model of the log-transformed, standardized protein levels and the additive reference allele counts from the most significant locus to adjust YKL-40 values and tested the differences in correlations with CSF Tau/A?42 ratio, A?42, tau, and ptau181.We found that genetic variants on the CH13L1 locus were significantly associated with CSF YKL-40 levels, but not AD risk, age at onset, or disease progression. The most significant variant is a reported expression quantitative trait locus for CHI3L1, the gene which encodes YKL-40, and explained 12.74 % of the variance in CSF YKL-40 in our study. YKL-40 was positively correlated with ptau181 (r?=?0.521) and the strength of the correlation significantly increased with the addition of genetic information (r?=?0.573, p?=?0.006).CSF YKL-40 levels are likely a biomarker for AD, but we found no evidence that they are an AD endophenotype. YKL-40 levels are highly regulated by genetic variation, and by including genetic information the strength of the correlation between YKL-40 and ptau181 levels is significantly improved. Our results suggest that studies of potential biomarkers may benefit from including genetic information.

Dataset Information

Chitinase-like protein YKL-40 correlates with inflammatory phenotypes, anti-asthma responsiveness and future exacerbations.

Publications

Chitinase-like protein YKL-40 correlates with inflammatory phenotypes, anti-asthma responsiveness and future exacerbations.

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