Serum YKL-40 Research Articles

Serum Biomarkers of Inflammation and Turnover of Joint Cartilage Can Help Differentiate Psoriatic Arthritis (PsA) Patients from Osteoarthritis (OA) Patients.

The aim of this study was to find characteristic biomarkers in the serum of patients with osteoarthritis (OA) and psoriatic arthritis (PsA) responsible for inflammation and destruction of joint cartilage, which could differentiate these two diseases. The study included 67 people: 22 patients with knee OA, 22 patients with PsA, and 23 individuals who were the control group of healthy individuals (HC). The concentration of IL-18, IL-20, IL-6, MMP-1, MMP-3, COMP, PG-AG, and YKL-40 in serum were determined. Among the OA and PsA patients group, the radiological assessment and clinical assessment were also performed. The concentration of 7 out of 8 of examined biomarkers (except MMP-1) was statistically significantly higher in the serum of patients with OA and PsA than in the control group. Compering OA and PsA groups only, the serum PG-AG level in OA patients was statistically significantly higher than in PsA patients (p < 0.001). The results of univariate and multivariate logistic regression analysis comparing OA and PsA biomarker serum levels identified PG-AG and COMP as markers that are significantly different between patients with OA and PsA (odds ratio 0.995 and 1.003, respectively). The ROC curve constructed using the model with age showed PG-AG and COMP had an AUC of 0.907. The results of this study show that COMP and PG-AG may be sensitive markers differentiating patients with osteoarthiritis from psoriatic arthritis.

Serum YKL-40 and IL 17 in Psoriasis: Reliability as prognostic markers for disease severity and responsiveness to treatment.

YKL-40, a mammalian chitinase 3- like protein that was associated with multiple inflammatory and immune diseases. Previous studies have suggested a role for YKL-40 in psoriasis based on its significantly higher levels in the serum of psoriatic patient compared with healthy controls. The aim of this study was to determine the correlation between serum YKL-40, psoriasis severity using PASI score and serum levels of IL-17 before and after narrow-band UVB therapy. 28 patients with moderate to severe plaque psoriasis, as defined by PASI scores, were enrolled in this prospective cohort study. All cases received NB-UVB phototherapy twice weekly for 3 months. Serum YKL-40 and IL-17 levels were evaluated before and after 3 months of treatment. Clinical photographs were taken both at baseline and after 3 months. There was a statistical positive correlation between serum levels of YKL-40 and serum IL-17 levels as well as PASI score in patients with moderate to severe psoriasis before and after treatment. YKL-40 represents a reliable marker for psoriasis severity estimated by PASI and positively correlated with IL 17 as an inflammatory marker in psoriasis.

YKL-40 as a clinical biomarker in adult patients with CF: Implications of a CHI3L1 single nucleotide polymorphism in disease severity

BackgroundYKL-40 (chitinase 3-like 1 gene; CHI3L1) is an inflammatory marker that is increased in the blood of patients with inflammatory diseases, including cystic fibrosis (CF). The objective of our study was to explore the relationship between circulating levels of YKL-40, selected CHI3L1 single nucleotide polymorphisms (SNPs) and the severity of CF disease. MethodsA prospective cohort of 188 adult patients with CF was established in 2015. Blood samples and clinical data were collected over 2 years to analyze the circulating levels of YKL-40 and to genotype selected CHI3L1 SNPs. We also looked for an association between these factors and clinical parameters. ResultsWe found that according to the serum YKL-40 concentration, the patients could be categorized into two distinct groups: low and high YKL-40. Compared to the patients in the low YKL-40 group, the patients in the high YKL-40 group had lower lung function (P < 0.001), a higher proportion of delF508 homozygote mutations (P= 0.027) and dysglycemia (P= 0.015). They were also more colonized with Pseudomonas aeruginosa (P= 0.003) and required more frequent antibiotic intravenous courses (P < 0.001). We also observed that patients expressing the C/C-rs4950928 genotype had higher levels of YKL-40 in their blood and were more frequently dysglycemic. ConclusionOur study suggests that YKL-40 could be a potential biomarker of CF disease severity. Furthermore, the CHI3L1 rs4950928 SNP could be a susceptible gene that could be used by CF health professionals to identify patients who are the most at risk of having a severe clinical profile.

Prognostic utility of serum YKL-40 in patients with cervical cancer

Inflammation is one of the hallmarks of cancer and plays a crucial role in the development and progression. The objective of the present study was to investigate if high serum YKL-40 is related to poor prognosis in cervical cancer (CC) patients. A prospective biomarker study of 116 patients with CC (FIGO stage Ia: n = 4; Ib: n = 55; II: n = 26; III: n = 26; IV: n = 5) and 152 patients with cervical intraepithelial neoplasia (CIN). The patients received primary surgery, radiotherapy and chemotherapy according to standard guidelines during the period 2001–2004. Seventy patients died during the follow-up period (median 117 months, range 104–131). Serum concentrations of YKL-40 were measured by ELISA. Serum concentrations of YKL-40 were increased (p < .001) in CC patients (median 76 µg/L, IQR 45–148) compared to CIN patients (44 µg/L, IQR 30–61) and healthy women (41 µg/L, IQR 29–58). YKL-40 was elevated (>age-corrected 95th percentile of YKL-40 in healthy women) in 30 (26%) of the CC patients. Univariate Cox analysis demonstrated that YKL-40 (included as a log-transformed continuous variable (base 2)) was associated with recurrence-free survival (RFS) (HR = 1.48, 95% CI: 1.11–1.98, p = .008) and overall survival (OS) (HR = 1.74, 1.44–2.10, p < .0001). Multivariate Cox analysis showed that stage (II + III vs. I: HR = 2.92, 1.37–6.20, p = .005), YKL-40 (HR = 1.35, 1.06–1.73, p = .018) and age (HR = 1.56, 1.21–1.99, p = .0005) were independent prognostic variables of OS. During treatment, a 2-fold increase in YKL-40 compared to baseline level was associated with short RFS (HR = 1.87, 1.27–2.77, p = .0016) and OS (HR = 1.78, 1.26–2.50, p = .0010). Serum YKL-40 is an independent biomarker of OS in patients with cervical cancer.

The inflammatory biomarker YKL-40 is elevated in the serum, but not the sputum, of E-cigarette users

Rationale: E-cigarettes are popular among youth and young adults and have been shown to be associated with pulmonary conditions such as asthma and COPD. YKL-40 may serve as a biomarker of pulmonary diseases and may predict the loss of pulmonary function among smokers. We hypothesized that similar to cigarette smokers, e-cigarette users will have higher levels of YKL-40 compared to non-tobacco users. Methods We conducted a cross-sectional study of adults between 18 and 55 years old. Inclusion criteria were: exclusive e-cigarette use or cigarette smoking for ≥ 1 year or no history of tobacco use. Participants with a history of pulmonary illness, atopy, medications (except birth control pills), marijuana, and illegal substance use were excluded. Custom Multiplex ELISA was used to measure YKL-40 and other biomarker levels in the serum and induced sputum of the participants. Multivariable linear regression was used to compare the levels of YLK-40 in healthy participants, e-cigarette, and cigarette users after adjusting for age, sex, and BMI. Results We recruited 20 healthy controls, 23 cigarette smokers, and 22 exclusive e-cigarette users. Serum YKL-40 (ng/ml) was significantly higher in e-cigarette users (Median 21.2 [IQR 12.1-24.0] ng/ml) when compared to controls (12.2 [IQR 8.7-18.1] ng/ml, p = 0.016) but comparable to cigarette smokers (21.6 [IQR 11.62-51.7] ng/ml, p = 0.31). No significant differences were found in the serum or sputum of the other biomarkers tested. Conclusion The inflammatory biomarker, YKL-40 is elevated in the serum but not the sputum of e-cigarette users with no reported pulmonary disease. Further research is necessary to characterize this association.

Serum IL6 as a Prognostic Biomarker and IL6R as a Therapeutic Target in Biliary Tract Cancers.

Biliary tract cancer (BTC) is a heterogeneous group of rare gastrointestinal malignancies with dismal prognosis often associated with inflammation. We assessed the prognostic value of IL6 and YKL-40 compared with CA19-9 before and during palliative chemotherapy. We also investigated in mice whether IL6R inhibition in combination with gemcitabine could prolong chemosensitivity. A total of 452 Danish participants with advanced (locally advanced and metastatic) BTC were included from six clinical trials (February 2004 to March 2017). Serum CA19-9, IL6, and YKL-40 were measured before and during palliative treatment. Associations between candidate biomarkers and progression-free survival (PFS) and overall survival (OS) were analyzed by univariate and multivariate Cox regression. Effects of inhibiting IL6R and YKL-40 were assessed in vitro, and of IL6R inhibition in vivo. High pretreatment levels of CA19-9, IL6, and YKL-40, and increasing levels during treatment, were associated with short PFS and OS in patients with advanced BTC. IL6 provided independent prognostic information, independent of tumor location and in patients with normal serum CA19-9. ROC analyses showed that IL6 and YKL-40 were predictive of very short OS (OS < 6 months), whereas CA19-9 was best to predict OS > 1.5 years. Treatment with anti-IL6R and gemcitabine significantly diminished tumor growth when compared with gemcitabine monotherapy in an in vivo transplant model of BTC. Serum IL6 and YKL-40 are potential new prognostic biomarkers in BTC. IL6 provides independent prognostic information and may be superior to CA19-9 in certain contexts. Moreover, anti-IL6R should be considered as a new treatment option to sustain gemcitabine response in patients with BTC.

Non-invasive diagnosis of endometriosis and moderate-severe endometriosis with serum CA125, endocan, YKL-40, and copeptin quadruple panel

Considering the complex pathogenesis of endometriosis, which is associated with many cellular or molecular processes, such as proliferation, angiogenesis, inflammation, we evaluated the diagnostic value of a quadruple panel of serum markers CA125, endocan, YKL-40 and copeptin, for the prediction of endometriosis and moderate – severe endometriosis. Seventy women with endometriosis and 70 women without endometriosis were evaluated. Serum CA125, endocan, copeptin and YKL-40 levels were significantly increased in women with endometriosis compared to the women without endometriosis and in the minimal – mild endometriosis group compared to the no-endometriosis group. YKL-40, endocan and copeptin levels were significantly increased in the moderate – severe endometriosis group compared to the mild –moderate endometriosis group but the difference in CA125 levels remained non-significant. The quadruple panel score had an AUC of 0.954, a sensitivity of 96.5% and specificity of 84.6% for prediction of moderate – severe endometriosis. Zero or one positive marker had a sensitivity of 91.4% and specificity of 88.57% to rule out endometriosis. In conclusion, a quadruple panel of serum markers-CA125, endocan, YKL-40, and copeptin may be beneficial for the diagnosis of endometriosis and especially moderate – severe endometriosis. Further studies are needed to prove the efficacy of this panel. Impact statement What is already known on this subject? Many serum markers including CA125 have been investigated so far and suggested to be associated with endometriosis. However, none of these markers is sensitive and specific enough to diagnose endometriosis. What do the results of this study add? A quadruple panel score (CA125, endocan, YKL-4 and copeptin) had an AUC of 0.954, a sensitivity of 96.5% and specificity of 84.6% for prediction of moderate – severe endometriosis. What are the implications of these findings for clinical practice and/or further research? A high score may be beneficial to warn the surgeon about the risk of moderate to severe endometriosis if the patient will be operated anyway. A negative test of the quadruple panel may show high odds that there is no endometriosis which may prevent unnecessary surgery.

Adenovirus vector-mediated YKL-40 shRNA attenuates eosinophil airway inflammation in a murine asthmatic model.

Recent studies have revealed that YKL-40 is involved in the pathogenesis of asthma. However, its specific mechanism remains unclear. The present study aims to investigate the effect of adenovirus vector-mediated YKL-40 short hairpin RNA (shRNA) on regulation of airway inflammation in a murine asthmatic model. Mice were assessed for airway hyperresponsiveness (AHR), total leukocytes and the percentage of eosinophil cells in bronchoalveolar lavage fluid (BALF). YKL-40 mRNA and protein expression levels were detected using quantitative real-time PCR and western blot assays. Enzyme-linked immunosorbent assay (ELISA) was used to detect YKL-40 and eosinophil-related chemokine expression levels in BALF and serum. Lung histology analyses were performed to evaluate the degree of inflammatory cell infiltration around the airway and airway mucus secretion.YKL-40 shRNA significantly inhibited the YKL-40 gene expression in asthmatic mice. In addition, YKL-40 shRNA alleviated eosinophilic airway inflammation, AHR, airway mucus secretion and decreased the levels of YKL-40 in BALF and serum in a murine asthmatic model. The levels and mRNA expression of IL-5, IL-13 in asthmatic mice lung tissues, eotaxin, and GM-CSF in BALF and serum significantly decreased. Bone marrow signaling molecules including IL-5, eotaxin, and GM-CSF were correlated with decreased levels of YKL-40. The study reveals that YKL-40 could be involved in asthma inflammation by altering bone marrow signaling molecules. YKL-40 gene RNA interference could provide new therapeutic strategies for asthma.

Assessment of Serum (YKL-40) As an Early Diagnostic Marker of Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus

Background: YKL-40 is an inflammatory marker, a positive association between elevated circulating YKL-40 levels and increasing levels of albuminuria, which have been described in patients with type 1 and type 2 diabetes indicating a role of YKL-40 in the progressing vascular damage resulting in microvascular disease. Objectives: To assess serum YKL-40 as an early diagnostic marker of diabetic nephropathy in type 2 diabetes mellitus. Patients and Methods: 70 patients with type 2 diabetes mellitus (46 males and 24 females) were included in this study, another 19 healthy volunteers (12 males and 7 females) were chosen as a control group (group I). Patients were further classified according to their Albumin/creatinine ratio into three groups: group II; Diabetic normoalbuminuric, group III; Diabetic microalbuminuric and group IV; Diabetic macroalbuminuric. All subjects (patients and controls) participating in the study were subjected to full history and clinical examination and routine laboratory investigations and also specific laboratory investigations include glycated hemoglobin (HbA1c), urine creatinine, microalbumin, albumin creatinine ratio, and serum YKL 40. Results: The present study showed that serum YKL-40 significantly increased in diabetic patients than in the control group. In addition, there was a significant increase of YKL-40 in the macroalbuminuric group compared to the normoalbuminuric group and microalbuminuric group and a significant increase of YKL-40 in a microalbuminuric group compared to the normoalbuminuric group. Conclusion: The serum levels of YKL-40 in type 2 DM were significantly higher than in normal patients, and its level increased with increasing urinary albumin excretion rate.

Early identification of carotid vulnerable plaque in asymptomatic patients

BackgroundThis study was to explore the influencing factors of atherosclerotic plaque formation and stability in patients with asymptomatic carotid atherosclerotic plaques, so as to identify the vulnerable plaques at early stage, and then find high-risk group of cardio-cerebrovascular events for early clinical intervention to reduce related mortality and disability.MethodsA total of 302 enrolled patients with asymptomatic carotid atherosclerotic plaques were divided into 3 groups based on the results of carotid artery color Doppler ultrasound: atherosclerotic unstable plaque (UP) group, atherosclerotic stable plaque (SP) group, and control group without plaques. Serum markers were measured by ELISA. χ2 test, t test, Pearson correlation analysis, and Logistic multivariate regression analysis were used in the analysis, and P < 0.05 was considered statistically significant.ResultsIt revealed that high MMP-9, LOX-1and YKL-40 were independent risk factors for unstable plaque formation. The area under the curve (AUC) of serum markers combined with MMP-9, LOX-1 and YKL-40 was 0.850, with sensitivity 87.67%, specificity 81.13%, and diagnostic accuracy 84.92%, which was significantly better than the individual diagnostic efficacy of other three factors. The accuracy rate of Crouse Plaque Score (CPS) in the diagnosis of vulnerable plaques was 61.90%, the 10-year ICVD diagnosis accuracy rate was 56.75%, and the diagnostic accuracy of serum markers was significantly better than CPS and 10-year ICVD.ConclusionNoninvasive cervical color Doppler ultrasound combined with serum markers MMP-9, LOX-1 and YKL-40 have significant early recognition effect on asymptomatic carotid vulnerable plaque patients.

Serum YKL-40 Levels Are Associated with the Atherogenic Index of Plasma in Children.

YKL-40, also known as chitinase-3-like protein 1, is an inflammatory glycoprotein that is secreted by various cell types under acute, chronic, and subclinical inflammation conditions. Elevated serum YKL-40 levels are reportedly independently related to diabetes mellitus, coronary artery disease, acute myocardial infarction, and cardiovascular mortality in adults. Therefore, we aimed to investigate the relationship between serum YKL-40 levels, lipid abnormalities, and the atherogenic index of plasma (AIP) in children. We enrolled 479 children aged 10–12 years (mean age: 11.52) in this general population-based, cross-sectional study. All subjects completed questionnaires and were subjected to multifrequency bioelectrical impedance analysis (BIA) to measure their height, weight, and body mass index (BMI). We collected serum samples from all participants to measure YKL-40, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels. Mean serum YKL-40 levels were significantly higher in the low-HDL-C (p = 0.017) and high-TG (p = 0.010) groups but were not related to TC and LDL-C levels. YKL-40 levels were also higher in the high AIP group (p = 0.007). After adjusting for age, gender, and BMI z-score, the associations between serum YKL-40 levels and TG levels (p = 0.003), the TG-to-HDL-C ratio (p = 0.019), and the AIP value (p = 0.012) remained significant. Based on these findings, we suggest that serum YKL-40 may be a useful initial screening tool or follow-up risk indicator for lipid abnormalities, atherosclerosis, and cardiovascular disease in children and adolescents with risk factors, regardless of obesity.

Levels of YKL-40 in pleural effusion and blood from patients with pleuritis.

In recent years, there have been a significant increase in the tests and biomarkers available for pleural fluid analysis. YKL-40 is one of the inflammatory biomarkers that is used for this purpose. The aim of our study is to assess the levels and diagnostic values of YKL-40 in patients with different types of pleural effusions (PE). This was a prospective, observational and crosssectional study. Pleural and serum YKL-40 levels were measured using enzyme-linked immunosorbent assay in 119 patients with PEs, including 23 transudates PE, 47 malignant PE, 26 parapneumonic PE (PPPE), 17 paramalignant PE (PME) and 6 tuberculous PE (TBPE). Median pleural YKL-40 level was higher in exudates (390.3 ng/mL) than in transudates (369.5 ng/mL) (p<0.02). For a cut-off level of 378 ng/mL, it was found to predict exudates with 70% sensitivity and 64% specificity. [area under the curve (AUC)= 0.660, p= 0.01]. Median pleural YKL-40 level was highest in PMEs (407.1 ng/mL) and the lowest in transudates (369.5 ng/ mL) and high levels, with a cut-off value of 396 ng/mL, differentiated PMEs from other subgroups with 65% sensitivity and 68% specificity. (AUC= 0.680, p= 0.02). Median serum YKL-40 level was the highest in PPPEs (351.4 ng/mL) and the lowest in TBPEs (114.2 ng/mL) (p= 0.01). For a cut-off level of 284 ng/mL, it differentiated PPPEs from TBPEs with 61% sensitivity and 100% specificity (AUC= 0.830, p= 0.01). In TBPEs, pleural/serum YKL-40 ratio was strongly related with pleural ADA (r= 1, p= 0.04). Pleural YKL-40 may be useful for differentiating exudates and detecting PMEs. Serum YKL-40 may be good diagnostic biomarker for differentiating PPPEs and TBPEs. Additionally, measuring serum and pleural YKL-40 and pleural ADA may be reliable way to diagnose TBPEs.

Can serum periostin, YKL-40, and osteopontin levels in pre-school children with recurrent wheezing predict later development of asthma?

Currently, there are no reliable clinical tools available for predicting asthma in pre-school-aged children with recurrent wheezing. The aim of this study was to evaluate the usefulness of serum periostin, YKL-40, and osteopontin biomarkers in wheezy pre-school-aged children for predicting the development of asthma in school ages. The study was prospectively conducted between 2011 and 2017. The clinical features of the pre-school-aged children with recurrent wheezing and the levels of serum periostin, YKL-40, and osteopontin were measured. The same participants were reevaluated in school-age period, and participants with asthma were identified. Relative risk (RR) for the development of asthma was analyzed. Of the 197 pre-school-aged children with recurrent wheezing who were reevaluated in school-age years, 32% of them had asthma. Serum periostin, YKL-40, and osteopontin levels at admission could not predict participants who would have asthma symptoms in school-age years. The RR for continuing of asthma symptoms was higher in participants who had their first wheezing episode before 1 year of age, preterm birth, cesarean section delivery, prenatal smoking exposure, multi-trigger wheezing, parental asthma, modified asthma predictive index positivity, prophylactic vitamin D intake ≤ 12 months, breastfeeding time ≤ 12 month, and aeroallergen sensitivity [RR (95% CI) and P value: 2.813 (1.299-6.091), 0.002; 1.972 (1.274-3.052), 0.009; 1.929 (1.195-3.114), 0.004; 2.232 (1.463-3.406), <0.001; 3.152 (1.949-5.097), <0.001; 1.730 (1.144-2.615), 0.016; 2.427 (1.559-3.777), <0.001; 2.955 (1.558-5.604), <0.001; 1.767 (1.084-2.881), 0.016; 0.765 (0.556-1.053), 0.016; respectively]. Results have shown that clinical features were more valuable than biomarkers in predicting having asthma in school-age years in participants who had recurrent wheezing in pre-school-age period.

Assessment of YKL-40, lipid profile, antioxidant status, and some trace elements in benign and malignant breast proliferation.

Breast cancer is mainly the common form of cancer in women and is a leading cause of death worldwide associated with cancer. The objective of this study was to assess the possible association of lipid profiles (total cholesterol TC, low-density lipoprotein LDL, very-low-density lipoprotein VLDL, high-density lipoprotein HDL, non-HDL and triglyceride TG), Chitinase-3-Like Protein1 (YKL-40) and changes in the levels of certain trace elements (Cu, Mg, Fe, and Zn), antioxidant status (TAC) and nitric oxide (NO) in benign and breast cancer in Egyptian females population. For 56 females with a benign breast tumor, 58 females with breast cancer, besides 52 healthy controls, Serum lipid profile, YKL-40, TAC, NO, Cu, Fe, Zn, and Mg have been determined. Our results showed a significant difference in lipid profile and a significant increase in, YKL-40, NO, and iron in breast benign tumor and cancer patients compared to control one. Besides, there is a significant reduction in serum magnesium and TAC levels in the patients' group compared to the healthy group. There is also a significant correlation between serum YKL-40 level and TC, LDL-C, VLDL-C, non-HDL-C, and TG in the breast cancer group; although only YKL-40 and VLDL-C showed a significant positive correlation in benign tumor patients. It is recommended that non-HDL-cholesterol, TAC, and Mg be used as biomarkers for breast cancer and its progression.

Postoperative serum CA19-9, YKL-40, CRP and IL-6 in combination with CEA as prognostic markers for recurrence and survival in colorectal cancer

Background In colorectal cancer (CRC) patients, guidelines only recommend measurement of preoperative carcinoembryonic antigen (CEA), although postoperative CEA may be more informative. However, the sensitivity of both preoperative and postoperative CEA in identifying relapse is limited. We studied whether CA19-9, YKL-40, C-reactive protein (CRP) and interleukin (IL)-6 add prognostic information combined with postoperative CEA. Material and methods This post-hoc analysis included 147 radically resected stage II (n = 38), III (n = 91) and IV (n = 18) CRC patients treated with adjuvant 5-fluorouracil (5-FU)-based therapy in the phase III LIPSYT study (ISRCTN98405441). We collected postoperative blood samples a median of 48 days after surgery. We analysed relapses, sensitivity, positive predictive value (PPV) and disease-free (DFS) and overall survival (OS) by bootstrap, Kaplan–Meier and adjusted Cox-models in the elevated vs. normal biomarker groups. Results Elevated postoperative CEA associated with impaired DFS (HR 7.23; CI95% 3.85–13.58), impaired OS (HR 7.16; CI95% 3.76–13.63), and more relapses (HR 7.9; CI95% 3.4–18.2); but sensitivity for CEA in finding relapses was only 31% (CI95% 21–48%). Normal CEA combined with an elevated YKL-40 or elevated CRP showed more relapses (HR for YKL-40 2.13 [CI95% 1.10–4.13], HR for CRP 3.14 [CI95% 1.21–8.16]), impaired DFS (HR 2.18 [CI95% 1.12–4.24] or 3.23 [CI95% 1.34–7.82]), and impaired OS (2.33 [CI95%1.24–4.40] or 2.68 [CI95%1.12–6.44]). Elevated CEA combined with a concomitantly elevated CA19-9, YKL-40, CRP or IL-6 showed a respective PPV of 100, 90, 100, and 100%. Conclusion In radically operated stage II to IV CRC patients who received adjuvant 5-FU-based chemotherapy, a postoperatively elevated CEA alone or in combination with CA19-9, YKL-40, CRP, or IL-6, or a normal CEA combined with an elevated YKL-40 or with an elevated CRP, may indicate patients at high risk of relapse.

Relationships between increased circulating YKL-40, IL-6 and TNF-α levels and phenotypes and disease activity of primary Sjögren's syndrome

BackgroundThere is now no single score or marker useful for evaluating disease activity of primary Sjögren's syndrome (pSS). This study was designed to explore the associations of circulating YKL-40, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) with systemic activity and phenotypes of pSS. MethodsThis study included 58 pSS patients and 30 healthy controls (HC). The sera were measured by multiplex immunoassay for YKL-40, IL-6 and TNF-α concentrations. The disease activity of pSS patients was evaluated by European league against rheumatism (EULAR) SS disease activity index (ESSDAI). Local severity was assessed in accordance with the Tarpley score. ResultsSerum YKL-40, IL-6 and TNF-α levels significantly elevated in pSS patients compared with those in HC (all P < 0.001). These cytokines correlated with ESSDAI, ESR, CRP, and IgG (all P < 0.05). Serum YKL-40 level correlated markedly with age (r = 0.405, P = 0.002), neutrophil count (r = 0.399, P = 0.002) and neutrophil-to-lymphocyte ratio (NLR) (r = 0.401, P = 0.002), while IL-6 did weakly with NLR (r = 0.296, P = 0.024) and C3 (r = 0.288, 0.036). Serum levels of all three cytokines were substantially lower in patients with eye/mouth dryness vs. those without (all P < 0.05). Additionally, patients with pulmonary, renal involvement or anemia had remarkably higher concentrations of YKL-40 (all P < 0.05), while those with leukocytopenia had lower levels (P = 0.01). Fever or anemia patients showed higher serum concentrations of IL-6 (both P < 0.05), while serum levels of TNF-α were much higher in patients with presence of ANA, anti-SSA or anti-SSB antibodies (All P < 0.05). Serum IL-6 level correlated strongly with YKL-40 (r = 0.452, P < 0.001) and TNF-α (r = 0.743, P < 0.001) in pSS patients. A significant correlation was also found between YKL-40 and TNF-α (r = 0.308, P = 0.022) . ConclusionThe circulating YKL-40, IL-6 and TNF-α levels increase in pSS, and all of them are significantly correlated with indicators (ESSDAI, ESR, CRP, and IgG) for systemic inflammation of pSS. Each cytokine is separately associated with specific pSS phenotype.

Elevated serum YKL-40, IL-6, CRP, CEA, and CA19-9 combined as a prognostic biomarker panel after resection of colorectal liver metastases.

The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with colorectal liver metastases. Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis. Patients with 2-5 elevated biomarkers were at an increased risk of relapse compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1-1.72) or postoperatively (HR 1.54, 95% CI 1.23-1.92). Patients with 2-5 elevated biomarkers were also at an increased risk of death compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39-2.24) or postoperatively (HR 1.83, 95% CI 1.44-2.33). The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.

Increased cerebrospinal fluid YKL-40 levels are associated with disease severity of neuromyelitis optica spectrum disorders

BackgroundNeuromyelitis optica spectrum disorders (NMOSD) is a severe immune-mediated inflammatory central nervous system (CNS) syndrome. YKL-40, as a new inflammatory marker, has been studied in many autoimmunity and CNS diseases. Our aim of this study was to investigate cerebrospinal fluid (CSF) and serum YKL-40 levels in patients with NMOSD and their association with disease severity. MethodsWe measured CSF and serum YKL-40 levels in 29 patients with NMOSD and 21 age- and sex-matched controls. We analyzed the associations between CSF YKL-40 levels and the clinical variables of NMOSD. ResultsCompared to controls, patients with NMOSD had significantly higher CSF YKL-40 levels. Moreover, CSF YKL-40 levels were positively correlated with the Expanded Disability Status Scale scores. ConclusionsYKL-40 could be a NMOSD severity biomarker and a potential target for NMOSD treatment.

Serum and synovial fluid concentrations of interleukin-18 and interleukin-20 in patients with osteoarthritis of the knee and their correlation with other markers of inflammation and turnover of joint cartilage.

IntroductionOsteoarthritis (OA) is the most common degenerative joint disease, and its aetiology is not entirely known. The aim of the study was to evaluate the involvement of interleukin-18 (IL-18) and interleukin-20 (IL-20) in the pathogenesis of knee OA and their correlations with other markers of inflammation and destruction of joint cartilage, as well as clinical and radiological changes.Material and methodsThe study included 25 patients with knee OA and a control group. The concentration of IL-18, IL-20, IL-6, MMP-1, MMP-3, COMP, PG-AG, and YKL-40 in serum and synovial fluid (SF) were determined. We also evaluated radiological lesions of the knee joint according to the Kellgren-Lawrence (K-L) scale, and clinical severity of the disease according to Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne Index.ResultsThe concentrations of IL-18 and IL-20 were statistically significantly higher in serum of patients with OA than in the control group (106.00 ±189.76 pg/ml vs. 16.73 ±16.99 pg/ml, p < 0.001, 17.69 ±13.45 pg/ml vs. 9.76 ±9.00 pg/ml, p < 0.014). Serum concentration of IL-18 positively correlated with MMP-3 (R = 0.58; p = 0.006) and YKL-40 (R = 0.48; p = 0.002). The degree of radiological advancement of OA (K-L scale) correlated positively with clinical evaluation (WOMAC, R = 0.74, p ≤ 0.001; Lequesne Index, R = 0.57, p = 0.003).ConclusionsThe analysis of ROC curves showed that IL-20 as well as COMP, MMP-3, and YKL-40 may be diagnostic markers of knee OA. The observations indicate that IL-18 potentially mediates mainly in intra-articular processes and IL-20 could be primarily responsible for the systemic inflammatory reaction.

Comparative effects of oral hypoglycemic drugs on serum YKL-40 level in type 2 diabetic patients.

Background:The prevalence of Type 2 diabetes mellitus and its associated micro and macro-vascular complications are globally rapidly increasing. Studies show that most diabetic complications are associated with an inflammatory response. YKL- 40, a novel biomarker for acute and chronic inflammation, has been proved to have a role in these complications. Many classes of antidiabetic drugs may have modulatory effects on inflammation beyond their glucose‐lowering activity. So, inThis study we evaluate comparative effects of metformin and glimepiride on ykl-40 serum level in type2 diabetic patients. Patients and method(s):In a parallel-group, randomized trial setting, 46 newly diagnosed, medication-naive type 2 diabetes patients were assigned to metformin (in divided doses, 500 -850 mg tablets three times daily) (n = 23) or glimepiride (1-4 mg once daily) (n = 23). Serum concentrations of YKL-40, along with HbA1c were measured at baseline visit and after 4 months. Result(s): Both drugs were equally effective to achieve glycemic control. However, metformin caused more significant reduction in YKL-40 concentrations after 4 months when compared to glimepiride (P < 0.05). Conclusion: /From the present study it is hypothesized that metformin is more effective than glimepiride in reduction of YKL-40 level (inflammatory diabetic complications).