Serum Concentrations Of YKL-40 Research Articles

Establishment of using serum YKL-40 and SCCA in combination for the diagnosis of patients with esophageal squamous cell carcinoma.

BackgroundElevated serum YKL-40 levels have been observed in various cancers. We evaluated the diagnostic performance of serum YKL-40 alone or in combination with the CEA, CYFRA21-1 and SCCA tumor markers for patients with esophageal squamous cell carcinoma (ESCC).MethodsYKL-40 was detected in ESCC cell lines and tissues by real-time RT-PCR, Western blotting and ELISA. YKL-40 protein expression was determined in 20 ESCC tumor tissues using immunohistochemistry. Serum YKL-40 was measured by ELISA in 126 healthy donors, 59 patients with benign esophageal diseases and 150 patients with ESCC. Serum CEA, CYFRA21-1 and SCCA were determined by electrochemiluminescence.ResultsYKL-40 mRNA and protein were observed in ESCC cancer cell lines, tissues and cell culture media, respectively. YKL-40 expression was observed in 17 of 20 ESCC samples (85%). Serum YKL-40 concentration was significantly elevated in patients with ESCC (Range: 6.95-502.10 ng/ml) compared with patients with benign diseases (Range: 1.21-429.30 ng/ml; P = 0.038) and healthy controls (Range: 2.56-132.26 ng/ml; P < 0.001). ROC curves demonstrated that serum YKL-40 has a sensitivity of 72.70%, a specificity of 84.13% and an AUC of 0.874 for the diagnosis of ESCC, which was superior to CEA (Sen: 8.00%; Spe: 96.80%, AUC = 0.652), CYFRA21-1 (Sen: 40.00%; Spe: 92.06%, AUC = 0.746) and SCCA (Sen: 32.67%; Spe: 94.44%, AUC = 0.789). The YKL-40 and SCCA combination was better for diagnosing ESCC (Sen: 82.00%, Spe: 79.37%, PPV: 82.55 and NPV: 78.74; AUC = 0.917) than the YKL-40 and CEA combination (Sen: 74.00%, Spe: 83.20%, PPV: 84.09 and NPV: 72.73; AUC = 0.877), the YKL-40 and CYFRA21-1 combination (Sen: 82.00%, Spe: 77.78%, PPV: 81.46% and NPV: 78.40%; AUC = 0.897) or the CEA, CYFRA21-1 and SCCA combination (Sen: 56.67%, Spe: 84.80%, PPV: 81.73 and NPV: 61.99; AUC = 0.831). Associations between serum YKL-40 levels and the clinic characteristics of ESCC were not significant, with the exception of age (p = 0.001).ConclusionsESCC tumor cells and tissues express YKL-40. Serum YKL-40 may be a potential biomarker for ESCC. Serum YKL-40 in combination with SCCA significantly increases the sensitivity of detecting ESCC.

Elevated pretreatment serum concentration of YKL-40: an independent prognostic biomarker for poor survival in patients with colorectal cancer.

Serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role of YKL-40 and its relationship with colorectal cancer are poorly understood. Pretreatment serum levels of YKL-40 were determined in 86 patients with colorectal cancer and from 20 healthy controls. The serum YKL-40 levels in colorectal cancer patients were compared with those in healthy controls, and we retrospectively assessed the association between serum YKL-40 levels and clinicopathological findings and progression-free survival. Colorectal patients had a median serum YKL-40 level of 216 ng/mL (range 22.3-1, 253.2 ng/mL). Expression of serum YKL-40 levels was significantly higher in colorectal cancer patients compared with healthy controls, and the median serum values were 216 and 62.5 ng/mL, respectively (p < 0.01). No correlation was observed between progression-free survival and the type of chemotherapy regimen used tumor stage, sex, or histologic types. Patients with high serum YKL-40 levels [greater than the median level for all patients (216 ng/mL)] had a significantly shorter survival than patients with serum YKL-40 levels below the median (median progression-free survival, 36 vs. 50 months; p = 0.003). In multivariate analysis, the serum YKL-40 level, and the presence of distant metastasis were independent, statistically significant prognostic factors. The pretreatment serum YKL-40 level was identified as a new, independent prognostic biomarker in patients with colorectal cancer and may help to determine the individual prognosis of these patients.

Prognostic effect of serum and tissue YKL-40 levels in bladder cancer

ObjectivesYKL-40 is a novel inflammatory serum protein shown to be associated with the presence and prognosis of several malignancies. However, its prognostic relevance has not yet been analyzed in bladder cancer (BC). Therefore, the aim of this study was to assess the tissue, serum, and urinary levels of YKL-40 and their prognostic value in BC. Methods and materialsYKL-40 gene expression levels were analyzed in frozen tissue samples of 91 patients with BC; YKL-40 concentrations were measured in 120 serum (101 patients with BC and 19 controls) and 154 urine samples (125 patients with BC and 29 controls). In 16 cases, corresponding serum samples collected before and after radical cystectomy were analyzed for YKL-40. Results were correlated with clinicopathological parameters and follow-up data. ResultsYKL-40 gene expressions and serum concentrations were higher in patients with BC compared with controls; however, urinary YKL-40 levels remained under the detection limit in both patients and controls. Higher tissue gene expressions and serum concentrations were associated with poor patients’ survival in the univariable analysis (P = 0.037 and 0.022, respectively), but only high YKL-40 serum levels proved to be independent prognostic factors in BC (hazard ratio = 1.755, 95% CI: 1.014–3.039, P = 0.045). We found no significant difference between preoperative and postoperative serum concentrations of YKL-40. ConclusionsYKL-40 serum levels are associated with the presence of BC and poor patients’ survival. The independent prognostic relevance of YKL-40 is of particular interest in patients with muscle-invasive BC treated with radical surgery. Our data suggest that BC tissue is not the main source of serum YKL-40 levels.

Pretransplant serum human chitinase-like glycoprotein YKL-40 concentrations independently predict bronchiolitis obliterans development in lung transplant recipients

Bronchiolitis obliterans syndrome (BOS) is the main long-term complication limiting survival after lung transplantation. There exists no cure for BOS and its mechanisms are not well understood. Early identification of BOS could therefore contribute to improvement of therapeutic and preventive measures. The human chitinase-like glycoprotein YKL-40 is involved in regulation of inflammatory tissue response and remodeling and is associated with pulmonary fibrosis. However, its role in BOS is unknown. A total of 57 recipients with irreversible fibrotic BOS and matched 85 recipients without BOS were retrospectively analyzed. Pretransplant serum samples were available at the time of the study. Serum and bronchoalveolar lavage samples were obtained at BOS diagnosis or at a comparable time point in patients without BOS. Additionally, serum samples were obtained 3 months later after BOS diagnosis or after the first sample in patients without BOS. YKL-40 concentrations were analyzed by enzyme-linked immunosorbent assay. Pretransplant serum YKL-40 concentrations were higher in recipients who developed BOS and were useful in identifying patients at high risk for BOS development (odds ratio, 1.3; 95% confidence interval, 1.01-1.9; P=.02). At BOS diagnosis, posttransplant YKL-40 concentrations were significantly elevated in the serum and bronchoalveolar lavage of patients with BOS compared with those without BOS at a comparable posttransplant time point. Of note, there was no significant association between serum YKL-40 concentrations and the frequency of acute rejection episodes. Elevated pretransplant serum YKL-40 concentration is associated with BOS development and could be an independent biomarker in early prediction and monitoring of BOS.

Serum YKL-40 levels are altered in endometriosis

Endometriosis is traditionally defined as the presence of endometrial glands and stroma in ectopic locations, especially the pelvic peritoneum, ovaries and rectovaginal septum. YKL-40, a new biomarker of inflammation, is secreted by activated macrophages and neutrophils in different tissues with inflammation. Serum concentrations of YKL-40 are elevated in patients with diseases characterized by inflammation. We aimed to investigate the possible association between serum YKL-40 levels and endometriosis. A total number of 88 women were recruited for this case–control study. About 53 patients with surgically proven endometriosis were included, while 35 patients without endometriosis comprised the control group. Patients were classified as having minimal, mild, moderate and severe disease in accordance with the severity. Two new groups were formed by combining patients with minimal and mild disease (Stage 1–2) and with moderate and severe disease (Stage 3–4). Serum YKL-40 levels were statistically higher in the endometriotic group compared to control group (p:0.001). YKL-40 levels were significantly higher in Stage 3–4 group compared to Stage 1–2 group (p values 0.001) as well. Correlation analysis revealed a positive correlation between serum YKL-40 levels and the stage of the disease. YKL-40 may be utilized as a marker for determining the severity of endometriosis.

Serum YKL-40 concentrations are elevated and correlated with disease severity in patients with obstructive sleep apnea syndrome

Inflammation plays a critical role in the pathogenesis of obstructive sleep apnea syndrome (OSAS). YKL-40 is a novel biomarker of systemic inflammation. We aim to detect serum YKL-40 concentrations in OSAS patients and to clarify their relationship with clinical severity of the disease. We enrolled 159 OSAS patients and 104 healthy controls. The presence and severity of OSAS was assessed by Apnea-hypopnea index (AHI). Serum YKL-40 concentrations were detected by enzyme-linked immunosorbent assay (ELISA). We demonstrated that serum YKL-40 concentrations were significantly elevated in OSAS patients than those in controls. Multivariate logistic regression including all variables revealed that YKL-40 was the significant and independent predictor for the present of OSAS. In OSAS patients, there is a significant positive correlation between increments in serum YKL-40 concentrations and severity of OSAS. Serum YKL-40 concentrations were independently and significantly correlated with AHI scores. These results suggest that YKL-40 could be used as a potential biomarker for predicting the development and progression of OSAS.

Protein and mRNA Levels of YKL-40 in High-Grade Glioma

Malignant gliomas are the most common type of primary malignant brain tumours, characterized by extreme proliferation and aggressive invasion. There is evidence for over-expression of the YKL40 gene in high-grade gliomas. The high serum levels of the glycoprotein are associated with poor prognosis of various inflammatory and tumour processes. We investigated the YKL40 mRNA level and protein expression in the tumour site and in the serum of high-grade glioma patients. The YKL-40 expression in 36 patients with glial tumours (astrocytoma grade III, glioblastoma) and 33 age-matched healthy persons was measured by gene analysis, immunohistochemistry and ELISA. YKL-40 serum levels in high-grade glioma patients compared to healthy subjects were significantly increased (P ≤ 0.05). A wide range of variability in YKL40 mRNA expression was found. YKL-40 staining in situ was more abundant in glioblastoma tissue than in anaplastic astrocytoma, with the lowest level in normal brain tissue. Our gene analysis revealed that in general, YKL40 mRNA in glioma patients was over-expressed versus normal brain. A significant correlation between YKL40 transcript and protein levels was observed (P ≤ 0.05). It could be speculated that the YKL-40 protein might contribute to glioblastomas’ specific biological characteristics that distinguish them from grade III gliomas. A complex investigation of YKL40 expression was performed at the molecular and cellular levels in human high-grade gliomas. Serum YKL-40 concentrations increased with tumour grade and correlated positively with transcript rate, being the highest in glioblastoma. We provide evidence for a relationship between YKL40 expression and the malignancy of glial tumours.

Serum YKL-40 levels as a novel marker of inflammation and endothelial dysfunction in patients with pseudoexfoliation syndrome

To evaluate serum levels of YKL-40 in patients with pseudoexfoliation syndrome (PEX) in comparison with those of age- and sex-matched healthy subjects. Forty patients with PEX (PEX group) and 40 age- and sex-matched control subjects (control group) were enrolled in the study. An enzyme immunoassay method using the commercially available test MicroVue YKL-40 was used to measure serum YKL-40 concentration. Systolic and diastolic blood pressures, serum levels of high sensitivity C-reactive protein (hsCRP), total cholesterol, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglycerides were also examined. The mean age was 54.4±7.6 (ranging 41-65) years in each group. The mean serum YKL-40 level of the PEX group was significantly higher than that of the control group (P<0.001). In addition, the mean serum HsCRP, total cholesterol, LDL, and triglycerides levels were significantly higher, and mean serum HDL level was significantly lower in the PEX group than in the control group (all P<0.001, excluding both P=0.002 for triglycerides and HDL levels). Further, the mean systolic and diastolic blood pressures were significantly higher in the PEX group than in the control group (P₁=0.001 and P₂=0.01, respectively). We have shown a relationship between PEX and elevated serum levels of YKL-40. We imply that a better understanding of the role of YKL-40 in the pathogenesis of endothelial dysfunction and atherosclerosis is necessary to develop new therapies for preventing or treating PEX. Further studies are warranted to clarify the clinical relevance of these findings.

Overexpression of YKL-40 Predicts Plaque Instability in Carotid Atherosclerosis with CagA-Positive Helicobacter Pylori Infection

ObjectivesYKL-40 has been demonstrated to be related to atherosclerosis, but its role in predicting plaque status and the outcome of carotid atherosclerosis (CAS) caused by CagA-positive helicobacter pylori remains unclear. This study was aimed to investigate the role of YKL-40 in predicting the outcome of carotid atherosclerosis with CagA-positive Helicobacter pylori infection.MethodsThe serum concentrations of YKL-40, C-reaction protein in 310 patients undergoing color Duplex assessment of carotid atherosclerosis were recorded and divided into 3 groups according to the infectious statuses of helicobacter pylori. We also examined serum YKL-40, C-reaction protein and the plaque morphology in animal model of carotid atherosclerosis with different types of helicobacter pylori infection.ResultsOverexpression of YKL-40 was only found in carotid atherosclerosis group with CagA-positive helicobacter pylori infection; C-reaction protein failed to distinguish different infectious statuses of helicobacter pylori infection. In patients with CagA-positive helicobacter pylori infection, elevated YKL-40 expression was accompanied by more severe clinical symptoms. We also confirmed similar findings in rabbit model of carotid atherosclerosis with CagA-positive helicobacter pylori infection. We found that in 7 rabbits treated with anti-helicobacter pylori therapy, the serum YKL-40 level decreased and the plaque became more stable.ConclusionOur findings suggested that increased serum YKL-40 level indicates plaque instability and more severe clinical symptoms of carotid atherosclerosis with CagA-positive helicobacter pylori infection. Compared with C-reaction protein, YKL-40 seems to be a more specific predictor of plaque status and outcome of carotid atherosclerosis with CagA-positive helicobacter pylori infection.

Novel Inflammatory Marker in Dialysis Patients: YKL‐40

YKL-40 has been introduced as a marker of inflammation in different clinical situations. The association between YKL-40 and inflammation in chronic renal failure patients has not been researched currently. The objectives of this study were to establish serum YKL-40 concentrations in dialysis patients with chronic renal failure compared to healthy subjects and to explore its relationships with a proinflammatory cytokine, interleukine-6 (IL-6) and an acute phase mediator, high sensitivity C-reactive protein (hs-CRP). The study population included hemodialysis patients (N = 43; mean age of 40.9 ± 14.5), peritoneal dialysis patients (N = 38; mean age of 45.8 ± 13.7) and healthy subjects (N = 37; mean age of 45.5 ± 10.6). Serum concentrations of YKL-40, IL-6, hs-CRP and routine laboratory measures were evaluated. Compared to the healthy subjects, hemodialysis and peritoneal dialysis patients had higher concentrations of YKL-40, IL-6, hs-CRP, as well as lower concentrations of hemoglobin, serum albumin and high density lipoprotein-cholesterol (P < 0.001). YKL-40 concentrations were positively correlated with serum creatinine (P < 0.001, r = 0.495), IL-6 (P < 0.001, r = 0.306), hs-CRP (P = 0.001, r = 0.306) levels and inversely correlated with hemoglobin (P = 0.002, r = -0.285), serum albumin (P < 0.001, r = -0.355) and high density lipoprotein-cholesterol (P = 0.001, r = -0.306). In multivariate regression analysis YKL-40 was associated with creatinine, serum albumin and hs-CRP concentrations after adjustments with covariates. Dialysis patients with chronic renal failure have elevated serum YKL-40 concentrations. Associations with standard inflammatory parameters suggest that YKL-40 might be a novel inflammatory marker in this population.

High YKL-40 Serum Concentration Is Correlated with Prognosis of Chinese Patients with Breast Cancer

This study aimed to investigate the association between serum YKL-40 and prognosis of breast cancer in a Chinese population. Expression of YKL-40 of 120 Chinese patients with breast cancer and 30 controls (benign breast lesions) was measured in tumor tissue by immunohistochemistry and in serum by ELISA. Differences in YKL-40 positivity grouped by specific patients’ characteristics were compared using Pearson Chi-square test for rates of intratumoral staining, one-way ANOVA with a Bonferroni post-hoc comparison, or two-sample t-test for mean YKL-40 serum concentrations. Factors associated with overall survival were identified by univariate and multivariate cox-regression analyses. YKL-40 was elevated in approximately 75% of Chinese patients with breast cancer. A significantly higher percentage of patients with YKL-40 positive tumors had larger tumor size, higher TNM stage, and/or lymph node metastasis. Significantly higher mean YKL-40 serum concentrations were observed in patient subgroups with invasive lobular carcinoma (P<0.0167), higher TNM stage (P<0.001), and positive lymph node metastasis (P<0.001). The estimated mean survival time of patients with YKL-40 positive tumors was significantly shorter than for patients with YKL-40 negative tumors (55.13 months vs 65.78 months, P = 0.017). Multivariable Cox-regression analysis identified a significant association of overall survival time with YKL-40 serum concentration. Patients with YKL-40 positive tumors had significantly shorter disease free survival times than those with YKL-40 negative tumors. We propose that the potential utility of YKL-40 intratumoral staining or serum concentration as a biomarker for breast cancer is greatest within 5 years of diagnosis.

TIMP-1/-2 and transient elastography allow non invasive diagnosis of cystic fibrosis associated liver disease

BackgroundCystic fibrosis (CF) associated liver disease develops in approximately 30% of CF patients. However, routine sensitive diagnostic tools are lacking. AimsWe aimed to compare the value of transient elastography and experimental fibrosis markers for the detection of liver disease in CF patients. Methods145 CF patients (75 children, 70 adults) were prospectively studied and received transient elastography. CF liver disease was diagnosed according to recent guidelines. Serum concentrations of YKL-40, HA, PIIIP, MMP-9, TIMP-1 and TIMP-2 were determined by ELISA. ResultsTransient elastography was increased in adults and children with CF hepatopathy compared to those without and exhibited a high diagnostic accuracy for CF liver disease. In adults with portal hypertension, elastography was further enhanced. TIMP-2 was elevated in adults with CF hepatopathy associated portal hypertension and exhibited a high diagnostic accuracy for portal hypertension in adults and for CF hepatopathy in children. TIMP-1 had a high diagnostic accuracy for CF hepatopathy in adults. Diagnostic sensitivities were increased when elastography and respective biomarkers were combined for the detection of CF hepatopathy and portal hypertension. ConclusionsTIMP-1 and TIMP-2 represent powerful biomarkers for CF associated liver disease and portal hypertension. Their determination may confirm and improve the diagnostic accuracy of transient elastography.

High YKL-40 levels predict mortality in patients with type 2 diabetes

AimsWe determined levels of the inflammatory marker YKL-40 in a population of patients with type 2 diabetes (T2D) and investigated the association with mortality. MethodsIn a prospective observational follow-up study, 290 patients with T2D, normoalbuminuria (n=177), microalbuminuria (n=71) and macroalbuminuria (n=42) were followed for a median (range) of 17.2 (0.2–23.0) years. Serum YKL-40 concentration was determined at baseline. ResultsBaseline median (IQR) YKL-40 level was 46ng/ml (36–67) in patients with normoalbuminuria, 61ng/ml (43–114) in microalbuminuric patients, and 81.5ng/ml (60–157) in patients with macroalbuminuria, p<0.001. During follow-up 189 patients (65.2%) died, 119 (41.0%) from cardiovascular causes. All-cause mortality was increased in patients with YKL-40 levels in the second and third tertile (hazard ratios (95% CI) compared with the first tertile, (1.50 (1.03–2.19), p=0.034, and 2.88 (2.01–4.12), p<0.001). This association persisted after adjustment for cardiovascular risk factors but was attenuated after additional adjustment for urinary albumin excretion rate and glomerular filtration rate.Cardiovascular mortality was increased with YKL-40 levels in the third tertile compared with the first tertile, (2.70 (1.78–4.08)), p<0.001. This association was diminished after adjustment for covariates. ConclusionsIn patients with T2D and increasing albuminuria high YKL-40 levels predict all-cause mortality.

YKL-40 and transient elastography, a powerful team to assess hepatic fibrosis

Objective. Transient elastography (TE) is a non-invasive and accurate method for the diagnosis of severe hepatic fibrosis and cirrhosis (F = 3 and F = 4). However, the assessment of significant fibrosis (F = 2) by TE is impaired due to a high variation in the diagnostic accuracy. Within this study, we aim to compare the diagnostic value of TE and experimental biomarkers of liver fibrosis. Material and methods. A total of 55 patients with chronic liver disease of different etiologies were included in the study. Among them, patients with HCV infection represented the largest cohort (n = 25). Liver fibrosis was evaluated according to the Desmet/Scheuer score. All patients received TE. Serum concentrations of YKL-40, hyaluronic acid (HA), Laminin, C-terminal procollagen I peptide, MMP-9, TIMP-1, TIMP-2 and MMP-9/TIMP-1 complex were determined by ELISA. Results. In the total patient population, areas under the receiver operator characteristic curve (AUROC) for TE were 0.798 (F ≥ 2), 0.880 (F ≥ 3) and 1 (F = 4). Among the serum markers, highest diagnostic accuracies were calculated for YKL-40 for F ≥ 2 (0.792) and F ≥ 3 (0.914) and for YKL-40 and HA for F = 4 (both 0.936). In the subgroup of HCV patients, the following AUROCs for TE were calculated: 0.802 (F ≥ 2), 0.798 (F ≥ 3) and 0.998 (F = 4). YKL-40 exhibited the highest diagnostic accuracy of all biomarkers in the HCV population (0.880, 0.854 and 0.986, respectively). Conclusions. YKL-40 is a powerful fibrosis marker with high diagnostic accuracy, in particular in HCV-associated liver disease. Its determination may confirm and improve the diagnostic accuracy of TE especially in early stages of liver fibrosis.

Comparison of Transient Elastography and Experimental Class I Fibrosis Markers for the Non-Invasive Assessment of Hepatic Fibrosis

Background and aims: Transient elastography (TE) is an established non-invasive and accurate method for the diagnosis of severe hepatic fibrosis and cirrhosis (F=3 and F=4). However, the assessment of significant fibrosis (F=2) by TE is impaired due to a high variation in the diagnostic accuracy. Within the present study, we compared the diagnostic value of TE and experimental biomarkers of hepatic fibrosis. Materials and Methods: 55 patients with chronic liver disease of different etiologies were included in the study. Among them, patients with HCV infection represented the largest cohort (n=25). Liver fibrosis was evaluated according to the Desmet/Scheuer score. All patients received TE. Serum concentrations of YKL-40, hyaluronic acid (HA), laminin, C-terminal procollagen I peptide, MMP-9, TIMP-1, TIMP-2 and the MMP-9/TIMP-1 complex were determined by ELISA. Results: In the total patient population, areas under the receiver operator characteristic curve (AUROC) for TE were 0.798 for F≥2, 0.880 for F≥3 and 1 for F=4. Among the serum markers, highest diagnostic accuracies were calculated for YKL-40 for F≥2 and F≥ 3 (0.792 and 0.914) and for YKL-40 and HA for F=4 (both 0.936). In the subgroup of HCV patients, the following AUROCs for TE were calculated: 0.802 (F≥2), 0.798 (F≥3) and 0.998 (F=4). YKL-40 exhibited the highest diagnostic accuracy of all serum markers measured in the HCV population (0.880, 0.854, and 0.986 respectively). Conclusions: YKL-40 is a powerful fibrosis marker with high diagnostic accuracy in particular in HCV associated liver disease. Its determination may confirm and improve the diagnostic accuracy of TE, especially in early stages of liver fibrosis.

Promoter polymorphisms in the chitinase 3-like 1 gene influence the serum concentration of YKL-40 in Danish patients with rheumatoid arthritis and in healthy subjects

IntroductionThe present study investigates the association between single nucleotide polymorphisms (SNPs) in the chitinase 3-like 1 (CHI3L1) gene and serum concentrations of YKL-40 in Danish patients with rheumatoid arthritis (RA) and healthy controls as well as the association with RA in the Danish population. The CHI3L1 gene is located on chromosome 1q32.1 and encodes the YKL-40 glycoprotein. YKL-40 concentrations are elevated in the serum of patients with RA compared to healthy subjects, and YKL-40 has been suggested to be an auto-antigen and may play a role in development of RA and in inflammation.MethodsEight SNPs in the CHI3L1 gene and promotor were genotyped in 308 patients with RA and 605 controls (healthy blood donors) using TaqMan allele discrimination assays. Serum concentrations of YKL-40 were determined by an enzyme-linked immunosorbent assay (ELISA).ResultsWe found significant association between the serum concentrations of YKL-40 and polymorphism in the CHI3L1 gene among both patients with RA and controls. The g.-131(C > G) polymorphism (rs4950928) was most strongly associated with age adjusted serum concentrations of YKL-40 in patients with RA (P < 2.4e-8) and controls (P < 2.2e-16). No significant allelic- or genotypic association with RA was found in this Danish cohort.ConclusionsWe suggest that the g.-131(C > G) promoter polymorphism has a substantial impact on serum concentrations of YKL-40 in patients with RA and healthy subjects. However, the polymorphism does not seem to confer risk to RA itself. The effect of CHI3L1 polymorphism on clinical outcome or the response to treatment in patients with RA remains to be investigated.

Role of Breast Regression Protein–39 in the Pathogenesis of Cigarette Smoke–Induced Inflammation and Emphysema

The exaggerated expression of chitinase-like protein YKL-40, the human homologue of breast regression protein-39 (BRP-39), was reported in a number of diseases, including chronic obstructive pulmonary disease (COPD). However, the in vivo roles of YKL-40 in normal physiology or in the pathogenesis of specific diseases such as COPD remain poorly understood. We hypothesized that BRP-39/YKL-40 plays an important role in the pathogenesis of cigarette smoke (CS)-induced emphysema. To test this hypothesis, 10-week-old wild-type and BRP-39 null mutant mice (BRP-39(-/-)) were exposed to room air (RA) and CS for up to 10 months. The expression of BRP-39 was significantly induced in macrophages, airway epithelial cells, and alveolar Type II cells in the lungs of CS-exposed mice compared with RA-exposed mice, at least in part via an IL-18 signaling-dependent pathway. The null mutation of BRP-39 significantly reduced CS-induced bronchoalveolar lavage and tissue inflammation. However, CS-induced epithelial cell apoptosis and alveolar destruction were further enhanced in the absence of BRP-39. Consistent with these findings in mice, the tissue expression of YKL-40 was significantly increased in the lungs of current smokers compared with the lungs of ex-smokers or nonsmokers. In addition, serum concentrations of YKL-40 were significantly higher in smokers with COPD than in nonsmokers or smokers without COPD. These studies demonstrate a novel regulatory role of BRP-39/YKL-40 in CS-induced inflammation and emphysematous destruction. These studies also underscore that maintaining physiologic concentrations of YKL-40 in the lung is therapeutically important in preventing excessive inflammatory responses or emphysematous alveolar destruction.

Effect of moxonidine and amlodipine on serum YKL-40, plasma lipids and insulin sensitivity in insulin-resistant hypertensive patients—a randomized, crossover trial

Moxonidine is a selective imidazoline receptor agonist with comparable blood pressure-lowering efficacy to first-line antihypertensives and favorable metabolic effects. YKL-40 (chitinase-3-1-protein) has been proposed as a new marker of inflammation, atherosclerosis and endothelial dysfunction in neoplastic, cardiovascular and metabolic diseases but has not yet been studied in the context of essential hypertension. Fifteen patients (10 M, 5 F; age 48+/-14 years) with arterial hypertension and insulin resistance (HOMA-IR index >2.77) on at least two antihypertensive drugs were randomized to receive either moxonidine (0.4 mg) or amlodipine (10 mg) for two 8-week periods with a 7-day wash-out. Serum insulin, glucose, C-reactive protein (CRP), lipids, uric acid, YKL-40 and blood pressure were measured and insulin sensitivity was calculated (HOMA) at the beginning and end of each study phase. Mean BP decreased significantly with both moxonidine and amlodipine (-9.8+/-7.6 and -10.4+/-7.3 mm Hg, respectively). Serum high-density lipoprotein cholesterol increased with both therapies, but only moxonidine-affected serum triglycerides. No significant changes in serum uric acid, CRP, YKL-40 (2.3 and 3.3 ng ml(-1), respectively) or HOMA index (0.70+/-2.4 and 0.76+/-2.8) were observed. There was a strong negative correlation between serum uric acid and YKL-40 concentration at baseline (r=-0.77, P=0.01). Serum YKL-40 did not correlate with blood pressure, biochemical parameters or HOMA index. Moxonidine is an effective adjunctive antihypertensive agent for use in patients with hypertension and insulin resistance that induces beneficial effects on serum lipid profile but does not reduce insulin resistance, inflammation or serum YKL-40 concentration.

Detection of bone erosions in knee osteoarthrosis by serum biomarkers

Osteoarthrosis (OA) is a degenerative chronic disease characterized by destruction of joint articular cartilage and subchondral bone with formation of osteophytes and usuries on joint surface. Quantitative and dynamic changes in remodeling of joint tissue reflect matrix molecules that dismiss as fragments in joint liquid, blood and urine where they can be detected. Human cartilage glycoprotein (YKL-40) is synthesised by chondrocytes and synovial cells and plays a significant role in remodel tissue. The aim of the paper was the parallel analysis and determination of the degree of correlation between ultrasound indicators destruction of joints, bone erosion (usuries), and serum YKL-40 concentrations in patients with primary osteoarthrosis of the knee. The analysis included 88 patients with the diagnosis of knee OA. Ultrasound review of knees was done by two rheumatologists. The analysis of serum samples determined the concentration of YKL40 by ELISA method. The average age of patients was 69.97 +/- 9.37 years, duration of knee OA 6.46 +/- 6.73 years. The mean value of age in 59 patients with usuries was 72.05 +/- 7.74, at 29 without usuries 65.75 +/- 11.00 (p = 0.003). The average value (median) thickness cartilage in medial condyl femur (front access) in patients with usuries was 1.25 mm (1.12-1.36 mm), without usuries 1.35 mm (1.20-1.51 mm) (p = 0.016). The central YKL40 value of biomarkers in the patients without usuries was 81 ng/ml (46.5-120.5 ng/ml), with usuries the medial condyil 138 ng/ml (89.5-175.0 ng/ml), the lateral 106 ng/ml (63.0-201.5 ng/ml) and both condyl 86 ng/ ml (69.75-140.5 ng/ml) (p = 0.004). The central value YKL40 after 5 year-duration of disease was 83.68 +/- 33.65 ng/ml, after 10 years 138.22 +/- 48.88 ng/ml, after 15 years 209.30 +/- 79.36 ng/ml, and after 20 years 218.50 +/- 106.51 ng/ml (p = 0.000). The biomarker YKL 40 may be a marker for usuries (area 0.691, p = 0.004; confidence interval 0.574-0.808). If you took the optimal cut-off of 84.5 ng/ml, then YKL40 sensitivity to the usuries was 69.5%, and specificity 51.7%. Increased concentrations of biomarkers YKL40 may be an indicator of the degree of destructive changes in the knee osteoarthrosis.

YKL-40 in Healthy Subjects

ABSTRACTYKL-40 is a plasma protein, belonging to the chitinase protein family, but has no chitinase activity. It is expressed and secreted by macrophages, chondrocytes, activated neutrophils, differentiated monocytes, vascular smooth muscle cell and cancer cells. The objective of the present study was to determine serum YKL-40 levels in healthy subjects and to develop a valid reproducible enzyme-linked immunosorbent assay. Serum YKL-40 concentrations were determined by a two-site, sandwich-type, enzyme-linked immunosorbent assay (ELISA) in 10 healthy female volunteers aged 18–50. Our investigation show a mean value 41,11 (20–59) ng/ml of serum YKL-40 in healthy women. We determined that the correlation between protein level and age is feeble, but positive. Our study is the first in Bulgaria to measure serum YKL-40 level in healthy subjects. Elucidation of YKL-40 functions in normal and pathologic processes is an important objective offuture analyses.