YKL-40 Levels In Patients Research Articles

Blood Astrocyte Biomarkers in Alzheimer Disease: A Systematic Review and Meta-Analysis.

Neuroinflammation, particularly early astrocyte reactivity, is a significant driver of Alzheimer disease (AD) pathogenesis. It is unclear how the levels of astrocyte biomarkers change in patients across the AD continuum and which best reflect AD-related change. We performed a systematic review and meta-analysis of 3 blood astrocyte biomarkers (glial fibrillary acidic protein [GFAP], chitinase-3-like protein 1 [YKL-40], and S100B) in patients clinically diagnosed with AD. MEDLINE and Web of Science were searched on March 23, 2023, without restrictions on language, time, or study design, for studies reporting blood levels of the astrocyte biomarkers GFAP, YKL-40, or S100B in patients on the AD continuum (including those with mild cognitive impairment [MCI] and dementia) and a cognitively unimpaired (CU) control population. AD diagnosis was based on established diagnostic criteria and/or comprehensive multidisciplinary clinical consensus. Studies reporting indirect biomarker measures (e.g., levels of biomarker autoantibodies) were excluded. Risk of bias assessment was performed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. Pooled effect sizes were determined using the Hedge g method with a random-effects model. The review was prospectively registered on PROSPERO (registration number CRD42023458305). The search identified 1,186 studies; 36 met inclusion criteria (AD continuum n = 3,366, CU n = 4,115). No study was assessed to have a high risk of bias. Compared with CU individuals, patients on the AD continuum had higher GFAP and YKL-40 levels (GFAP effect size 1.15, 95% CI 0.94-1.36, p < 0.0001; YKL-40 effect size 0.38, 95% CI 0.28-0.49, p < 0.0001). Both biomarkers were elevated in more advanced clinical stages of the disease (i.e., in AD dementia compared with MCI due to AD: GFAP effect size 0.48, 95% CI 0.19-0.76, p = 0.0009; YKL-40 effect size 0.34, 95% CI 0.10-0.57, p = 0.0048). No significant differences in blood S100B levels were identified. We demonstrated significant elevations in blood GFAP and YKL-40 levels in patients on the AD continuum compared with CU individuals. Furthermore, within the AD clinical spectrum, significant elevation correlated with more advanced disease stage. Our findings suggest that both biomarkers reflect AD-related pathology. Our findings are limited by the lack of cultural and linguistic diversity in the study populations meta-analyzed. Future meta-analyses using a biomarker-defined AD population are warranted.

Serum YKL-40 Levels in Patients with Rheumatoid Arthritis and Its Relationship with Disease Activity

Serum YKL-40 Levels in Patients with Rheumatoid Arthritis and Its Relationship with Disease Activity

Increased Circulating Levels of YKL-40 Protein in Children and Adolescents with Hemophilia: Correlation with the Degree of Hemophilic Arthropathy

Introduction: Hemophilia A and B are rare X-linked inherited bleeding disorders caused by complete or partial deficiency of coagulation factors VIII and IX, respectively. Recurrent joint bleeding (hemarthrosis) is the most frequent clinical manifestation of severe hemophilia. Unless appropriately managed, even subclinical hemarthrosis can lead to hemophilic arthropathy, that severely affects the quality of life of patients. Chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is a 40-kDa heparin-human cartilage glycoprotein without enzymatic activity, that is encoded by the CHI3L1 gene in humans and its name derives from the one letter code for the three terminal amino acids - tyrosine (Y), lysine (K) and leucine (L). YKL-40 is secreted in vitro and in vivo in the arthritic joint by various cell types, such as activated macrophages, chondrocytes, synoviocytes and neutrophils. Actually, it is a major protein that has been identified in the chondrocytes from arthritic knee joints.In fact, synovial as well as serum YKL-40 levels are found increased in joint diseases like rheumatoid arthritis and osteoarthritis, indicating its potential role as a biomarker of inflammation and tissue remodeling or degradation, whereas it is absent in normal joints. In our knowledge, there are not any reports linking YKL-40 expression with hemophilic arthropathy, thus we aimed to investigate if this protein could be implicated in hemophilic arthropathy severity, by measuring its circulating levels and correlate them with hemophilic arthropathy features and laboratory parameters in children and adolescents with hemophilia A and B. Patients and Methods: Eighty children and adolescents (median age:14 years, range 10-18 years) with severe (n= 60), moderate (n= 8) and mild (n= 12) hemophilia A or B (n= 7), on prophylaxis or on demand treatment (n= 12) were included in the study, while 35 apparently healthy male individuals matched for age served as controls. No signs of hemophilic arthropathy (NHAP), i.e. Hemophilia Joint Health Score 2.1 ≤ 2 and Hemophilia Early Detection Arthropathy with Ultrasound Score ≤ 1, were detected in 34/80 patients with median age of 13.5 years. In 37/80 patients with median age of 14.25 years arthropathy (HAP) was confirmed, while 18/80 patients with median age of 15.75 years presented with acute bleeding (AB)-hemarthrosis or muscle bleed- at the time of the laboratory evaluation. In patients and controls YKL-40 concentrations were determined by means of an immunoenzymatic technique. Results: We found that: a) Circulating YKL-40 levels in patients with hemophilia were significantly higher compared to controls, 21.9±2.3 ng/mL (95% Confidence Intervals of the mean (CI): 19.6;24.2 ng/mL) vs 17.0±2.5 ng/mL (CI: 14.5;19.4 ng/mL), respectively, p=0.003. b) Patients with arthropathy (HAP) tend to express higher circulating YKL-40 levels (25.5±2.0 ng/mL) than patients without arthropathy (NHAP)(20.1±1.8 ng/mL) and patients with acute bleeding (AB) (19.7±2.4 ng/mL), respectively, p-trend=0.06. Conclusions: To the best of our knowledge, this is the first study to evaluate the potential clinical significance of circulating YKL-40 levels in patients with hemophilia and demonstrated that it could reflect hemophilic arthropathy activity in clinical or even in subclinical level. As YKL-40 in synovial fluid is derived from cells in the inflamed/damaged synovium, such as chondrocytes, we postulate that it may be involved in the pathophysiology of the hemophilic arthropathy processes and reflect local disease activity. Further studies are essential on the role of YKL-40 in the evolution of hemophilic arthropathy, in order to fully elucidate its clinical significance and prognostic utility.

Elevated cerebrospinal fluid YKL-40 levels in patients with anti-gamma-aminobutyric- acid-B receptor encephalitis

ObjectiveAnti-gamma-aminobutyric-acid-B receptor (GABAbR) encephalitis is a rare form of autoimmune encephalitis. Until now, there are few biomarkers that can indicate the severity and prognosis of patients with anti-GABAbR encephalitis. The objective of this study was to exam the changes of chitinase-3-like protein 1 (YKL-40) in patients with anti-GABAbR encephalitis. In addition, whether YKL-40 could indicate the disease severity was also evaluated. MethodsThe clinical features of 14 patients with anti-GABAbR encephalitis and 21 patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis were retrospectively studied. YKL-40 levels in serum and cerebral fluid (CSF) of patients were detected by enzyme-linked immunosorbent assay. The correlation of modified Rankin Scale (mRS) score of encephalitis patients and YKL40 levels were analyzed. ResultsYKL-40 levels in CSF were significantly higher in patients with anti-GABAbR encephalitis or anti-NMDAR encephalitis than those in controls. YKL-40 levels between these two encephalitis groups were not different. Moreover, YKL-40 levels in CSF from patients with anti-GABAbR encephalitis were positively correlated with the mRS score at admission and at 6-month follow-up. ConclusionYKL-40 level is elevated in CSF from patients with anti-GABAbR encephalitis at early disease stage. YKL-40 may be a potential biomarker indicating the prognosis of patients with anti-GABAbR encephalitis.

Serum YKL-40 Levels in Patients with Asthma or COPD: A Pilot Study.

Background and Objectives: Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are not only common obstructive respiratory conditions but also major causes of morbidity and mortality worldwide. There is, however, a surprising lack of blood-based biomarkers for separating between these pulmonary disorders. The aim of this study was to assess the practical relevance of using serum YKL-40, single or combined, for this purpose. Materials and Methods: Subjects included Romanian patients with BA (n = 24) or COPD (n = 27). YKL-40, fibrinogen, pre-treatment C-reactive protein (CRP), post-treatment CRP, erythrocyte sedimentation rate, interleukin 6 (IL-6), procalcitonin (PCT), absolute neutrophil count, neutrophil percentage, absolute lymphocyte count, lymphocyte percentage, absolute eosinophil count, and eosinophil percentage were measured and compared between these patients. Results: This is the first study investigating the clinical significance of serum YKL-40 in delineating between COPD and BA in Caucasian populations. Only fibrinogen and YKL-40 levels were different between COPD and BA, with the measured values being significantly elevated. These patients exhibited distinct inflammatory profiles. Using the upper quartiles of these variables for the pooled study population (YKL-40: 5100 pg/mL; fibrinogen: 552 mg/dL) as cut-off values, subjects were classified into high or low groups. High YKL-40 adults revealed significantly increased PCT levels. High fibrinogen subjects, by contrast, showed significantly elevated IL-6 concentrations and pre-treatment CRP levels. Low YKL-40 and fibrinogen patients showed the absence of COPD. Conclusions: Combined use of serum YKL-40 and fibrinogen may be useful for identifying the absence of COPD.

Assessment of Serum Levels of YKL40 in Patients with Ulcerative Colitis

IBD is a recurring chronic intestinal disease classified into two subtypes: Crohn’s disease (CD) and ulcerative colitis (UC). YKL-40 is released by macrophages and neutrophils and is a growth factor for vascular endothelial cells and fibroblasts. Elevated blood concentrations of YKL-40 are detected in individuals with illnesses defined by inflammation or continuing fibrosis. The purpose of this study was to determine the relationship between serum YKL-40 and clinical disease activity in individuals with ulcerative colitis (UC). Identifying the cause of the elevation can be considered one of the most important ways to help the specialist in identifying UC patients prior to endoscopy.

Diagnostic value of YKL-40 for patients with asthma: A meta-analysis.

Objective: YKL-40 is a highly conserved and chitin-bound human glycoprotein in mammals that is associated with airway inflammation and has no enzyme activity. We aimed to conduct a meta-analysis to assess the use of YKL-40 levels as a diagnosis of asthma. Methods: A meta-analysis was conducted based on the data from medical literature data base searches with time restrictions of January 2007 to January 2021. We searched and extracted relevant information from a total of 15 studies that reported YKL-40 levels in patients with asthma and in healthy controls, and obtained a sample of 1647 patients with asthma and 1259 healthy controls. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated for this study by using statistical software packages. Results: Serum YKL-40 levels were higher in the patients with asthma than in the healthy controls (SMD 1.36 ng/ml [95% CI, 0.82-1.89 ng/ml]). YKL-40 levels are elevated in pediatric patients with asthma (SMD 2.26 ng/ml [95% CI, 1.33-3.18 ng/ml]) and in adult patients with asthma (SMD 0.96 ng/ml [95% CI, 0.26-1.66 ng/ml]). In addition, a subgroup analysis of asthma disease status showed that YKL-40 levels were significantly increased in the patients with stable asthma (SMD 1.69 ng/ml [95% CI, 0.81-2.56 ng/ml]) and in those with acute exacerbation asthma (SMD 3.31 ng/ml [95% CI, 2.04-4.58 ng/ml]), and serum YKL-40 levels were significantly higher in patients with acute exacerbation asthma than in patients with stable asthma (SMD 1.49 ng/ml [95% CI, 0.50-2.48 ng/ml]). Conclusion: Results of this meta-analysis suggested that increased serum levels of YKL-40 in patients with asthma could be used as an emerging indicator for distinguishing individuals with asthma from healthy individuals.

Associations between YKL-40 and markers of disease severity and death in patients with necrotizing soft-tissue infection

BackgroundNecrotizing soft-tissue infection (NSTI) is a severe and fast-progressing bacterial infection. Prognostic biomarkers may provide valuable information in treatment guidance and decision-making, but none have provided sufficient robustness to have a clinical impact. YKL-40 may reflect the ongoing pathological inflammatory processes more accurately than traditional biomarkers as it is secreted by the activated immune cells, but its prognostic yields in NSTI remains unknown. For this purpose, we investigated the association between plasma YKL-40 and 30-day mortality in patients with NSTI, and assessed its value as a marker of disease severity.MethodsWe determined plasma YKL-40 levels in patients with NSTI (n = 161) and age-sex matched controls (n = 65) upon admission and at day 1, 2 and 3.ResultsBaseline plasma YKL-40 was 1191 ng/mL in patients with NSTI compared with 40 ng/mL in controls (p < 0.001). YKL-40 was found to be significantly higher in patients with septic shock (1942 vs. 720 ng/mL, p < 0.001), and in patients receiving renal-replacement therapy (2382 vs. 1041 ng/mL, p < 0.001). YKL-40 correlated with Simplified Acute Physiology Score II (Rho 0.33, p < 0.001). Baseline YKL-40 above 1840 ng/mL was associated with increased risk of 30-day mortality in age-sex-comorbidity adjusted analysis (OR 3.77, 95% CI; 1.59–9.24, p = 0.003), but after further adjustment for Simplified Acute Physiology Score II no association was found between YKL-40 and early mortality.ConclusionHigh plasma YKL-40 to be associated with disease severity, renal-replacement therapy and risk of death in patients with NSTI. However, YKL-40 is not an independent predictor of 30-day mortality.

Serum YKL-40 levels in patients with multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system. The YKL-40 protein, which is secreted from various cells that contribute to inflammation and infection, plays a role in immune regulation. This study investigated the serum YKL-40 levels of patients with clinically isolated syndrome (CIS) and MS. The participants was divided into three groups: 1) patients with CIS (n = 20); 2) patients with relapsing-remitting MS (RRMS; n = 39); and 3) healthy individuals (n = 35). The YKL-40 levels in serum samples obtained from the participants were measured using enzyme-linked immunoassays. The median serum YKL-40 level was 20.2 ng/mL (range 9.8-75.9 ng/mL) in the patients with CIS, 22.7 ng/mL (range 13.4-57.9 ng/mL) in the patients with RRMS and 11.0 ng/mL (range 10.0-17.3 ng/mL) in the control group (p < 0.001). The serum YKL-40 levels in the patients with RRMS were correlated with the patients' expanded disability status scale scores and ages (p < 0.05). No relationships were determined between the serum YKL-40 levels and the other variables (p > 0.05). The serum YKL-40 levels were higher in the CIS group than in the MS group. These findings show that the serum YKL-40 levels were high even at the beginning of the disease. The serum YKL-40 levels were also not involved in the progression to clinically definite MS. The findings from this study suggested that YKL-40 may be a useful marker for the inflammatory process of MS.

Can YKL-40 be used as a biomarker for interstitial lung disease?: A systematic review and meta-analysis.

Background:Interstitial lung disease (ILD) has a poor prognosis and lacks specific biomarkers for early diagnosis, assessment of disease severity, and prognosis. YKL-40 levels were found to be elevated in patients with ILD, but these results are inconsistent. Therefore, we conducted a systematic review and meta-analysis to accurately study the relation between YKL-40 and ILD.Methods:We performed a systematic literature search in many databases (PubMed, Embase, the China National Knowledge Infrastructure, and Wanfang databases) and commercial Internet search engines to identify studies involving the role of YKL-40 in patients with ILD. The weighted mean difference with its 95% confidence interval were used to investigate the effect sizes. If obvious heterogeneity was found in the meta-analysis, the level of YKL-40 was directly compared by the Mann-Whitney test.Results:Sixteen eligible articles were finally identified. The results showed that the serum YKL-40 levels of patients with idiopathic pulmonary fibrosis, connective tissue-related ILD, sarcoidosis, cryptogenic tissue pneumonia, asbestosis-ILD, and idiopathic nonspecific interstitial pneumonia were higher than those in controls, but there was no increase in patients with pulmonary alveolar proteinosis. We also found that there are certain differences in the serum YKL-40 levels in patients with different types of ILD. The results showed that the bronchoalveolar lavage fluid YKL-40 levels of patients with idiopathic pulmonary fibrosis were significantly higher than that in controls. A systematic review indicated that there were correlations between the serum YKL-40 levels and lung function in patients with different ILD. In addition, YKL-40 may be used as a valuable biomarker for survival, with risk ratios ranging from 1.006 to 10.9.Conclusions:This study suggests that YKL-40 may be a useful biomarker for the diagnosis and prognosis of ILD.

Increased levels of YKL-40 in patients with diabetes mellitus: a systematic review and meta-analysis

BackgroundDiabetes mellitus (DM) could be classified as type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) and others according to etiology and pathology. Diabetic nephropathy (DN) is one of the most serious complications of DM. YKL-40 is a marker of inflammation and some studies have indicated that DM was related with inflammation. The objective of our study is to perform a systematic review and meta-analysis to confirm the relationship between YKL-40 and DM as well as DN.MethodsPubmed, Embase, CNKI and Chinese wanfang databases were searched for eligible studies by two independent authors. Studies were included in this meta-analysis if they fulfilled the following inclusion criteria: (1) a study involving the role of YKL-40 in DM (or DN) designed as a case–control study or cohort study; (2) the data of serum YKL-40 levels were available; (3) studies were published in English or Chinese. Finally, twenty-five studies were included in this meta-analysis.ResultsCompared with healthy controls, DM patients had significantly higher levels of YKL-40 (DM: SMD = 1.62, 95% CI 1.08 to 2.25, P = 0.000; GDM: SMD = 2.85, 95% CI 1.01 to 4.70, P = 0.002). Additionally, DM patients with different degree of albuminuria had significantly higher levels of YKL-40 compared with healthy controls (normoalbuminuria: SMD = 1.58, 95% CI 0.59 to 2.56, P = 0.002; microalbuminuria: SMD = 2.57, 95% CI 0.92 to 4.22, P = 0.002; macroalbuminuria: SMD = 2.69, 95% CI 1.40 to 3.98, P = 0.000) and serum YKL-40 levels increased with increasing severity of albuminuria among DM patients (microalbuminuria vs normoalbuminuria: SMD = 1.49, 95% CI 0.28 to 2.71, P = 0.016; macroalbuminuria vs microalbuminuria: SMD = 0.93, 95% CI 0.34 to 1.52, P = 0.002).ConclusionsOur current meta-analysis demonstrates that serum level of YKL-40 is increased in DM and positively associated with the severe degree of albuminuria. Therefore, we suggest that YKL-40 could be considered to be detected, along with other inflammatory markers, if DM, especially DN, is suspected.

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.

Chitinase 3-like 1 gene (T/C) polymorphism and serum YKL-40 levels in patients with hepatocellular carcinoma

The chitinase 3-like 1 (CHI3L1) gene encodes the YKL-40 protein. Serum YKL-40 levels are controlled by polymorphisms in the CHI3L1 gene. We aimed to examine the association of the rs880633 (T/C) polymorphism in the CHI3L1 gene with serum YKL-40 levels and to evaluate the role of this polymorphism as a risk factor for HCC and its effect on patient survival. A total of 225 subjects were categorized into two groups: group I included 120 patients with HCC, and group II involved 105 age and gender-matched healthy volunteers. Genotypes of the rs880633 (T/C) polymorphism in the CHI3L1 gene were analyzed using an allele discrimination assay with real-time PCR, and serum YKL-40 levels were determined using an ELISA technique. A significant difference in the genotype frequency of the T/C polymorphism in the CHI3L1 gene was observed between the two groups, with an increase in the frequency of the CC genotype observed among patients with HCC. Regarding the allelic distribution, the C allele was significantly predominant in patients, with HCC presenting with an increased HCC risk compared to the T allele. Subjects with the CC genotype had the highest serum YKL-40 levels, followed by those with the TC genotype, while subjects with the TT genotype had the lowest serum YKL-40 levels. An analysis of the overall survival of HCC patients revealed that patients with both the CC and CT genotypes displayed a significantly shorter survival rate than patients carrying the TT genotype. ConclusionsThe rs880633 polymorphism in the CHI3L1 gene may be a risk element for HCC. Patients with the CC genotype displayed the highest serum YKL-40 levels, which were linked to poor prognosis.

Plasma YKL-40: a Potential Biomarker for Tumor Invasion in Esophageal Cancer.

YKL-40, a chitinase-like glycoprotein has been identified as a candidate tumor marker. The current study evaluated the clinical significance of plasma YKL-40 in esophageal cancer patients. We enrolled 127 esophageal cancer patients, 29 healthy controls. Plasma YKL-40 levels were measured through enzyme linked immunosorbent assay. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficiency of plasma YKL-40 in esophageal cancer patients. The correlations between plasma YKL-40 and clinicopathological characteristics of esophageal were analyzed. Plasma YKL-40 levels were significantly higher in patients with lymph node metastasis than those that were non-metastatic (p = 0.005). Patients with tumor thrombus formation presented with significantly higher YKL-40 levels than those without thrombus formation (160.3 vs. 74.7 ng/mL, p = 0.012). YKL-40 levels in patients with advanced stage (III and IV) were significantly higher than those in the early stages (I and II, p = 0.016). ROC curve analysis showed that the area under curve was 0.909, and the best diagnostic threshold of YKL-40 for esophageal cancer was 80.6 ng/mL with 68.9% sensitivity and 96.6% specificity. This study indicated that YKL-40 may be a biomarker for esophageal cancer and potential biomarker for identification of invasive esophageal cancer.

Determination of serum YKL-40 levels in patients with brucellosis

Aim: To determine serum YKL-40 levels in patients diagnosed with brucellosis. Material and Methods: This study included 40 Brucellosis patients with positive serum agglutination tests and 41 healthy control subjects. The two groups were compared with regard to their serum YKL-40, hematological parameters, and C-reactive protein (CRP) values. Results: The brucellosis patient group presented YKL-40 values of 15.0 ± 8.8 ng/mL, CRP values of 0.2 ± 0.1 mg/dL, a Neutrophil/Lymphocyte ratio (NLR) of 1.5 ± 1.0, and a Platelet/Lymphocyte ratio (PLR) of 109.3 ± 46.4. The control group presented YKL-40 values of 12.7 ± 6.1ng/mL, CRP values of 1.48 ± 2.1mg/dL, a Neutrophil/Lymphocyte ratio (NLR) of 2.1 ± 0.7, and a Platelet/Lymphocyte ratio (PLR) of 147.8 ± 59.0. Conclusion: No significant differences were determined between the YKL-40 levels of the patient and control groups. The patient group manifested significantly higher levels of CRP compared to the control group, and YKL-40 was determined to be positively correlated with CRP, PLT, PLR, NLR and age. However, further studies are needed for the role of YKL-40 in infectious diseases to be understood more clearly.

Elevation in Circulating YKL-40 Levels in Patients with Stroke: A Review and Meta-Analysis

Background: Stroke is the second most common cause of mortality and the third most common cause of disability. Modifiable risk factors for ischemic stroke include obesity, diabetes, hypertension, cigarette smoking, atrial fibrillation, dyslipidemia, carotid artery stenosis, sickle cell disease, postmenopausal hormone therapy, poor diet, and physical inactivity. There is data establishing the role of atherosclerosis in stroke. Evidence suggests a role for inflammation in the development of atherosclerosis and cerebrovascular disease. YKL-40, also called chitinase-3-like-1 (CHI3L1), is a novel inflammatory biomarker secreted by monocytes which has been elevated in stroke patients in multiple studies. Objective: The aim of this study was to assess if patients with elevated YKL-40 have increased odds of having a stroke. Methods: PubMed, Embase, CINAHL, Cochrane, Web of Science, and google scholar were searched using the keywords YKL-40, chitinase-3-like-1 (CHI3L1), human cartilage glycoprotein 39 (HC-gp39), stroke, ischemic stroke, cerebrovascular disease, atherosclerosis, and inflammation. English studies from 1960 to August 2017 addressing YKL-40 and stroke as well as YKL-40 levels in subjects with and without stroke were analyzed. YKL-40 levels were converted to ng/mL if provided in any other scale. Results: Ten studies met the inclusion criteria. Twelve datasets were analyzed, as 1 study included more than 1 dataset. Seven studies were case-control studies (n = 702 cases and n = 389 controls), while 3 studies were cross-sectional (n = 13,811). A random effects model was used. The standardized mean difference in YKL-40 levels between the stroke group and the control group was 2.21 (1.28–3.14, p < 0.001). Sensitivity analysis and cumulative analysis showed unchanged results. Funnel plots/precision plots indicated publication bias. Meta-regression analysis of case-control studies for the variables age and gender showed no significant impact of age (p = 0.33) and male gender (p = 0.11). Conclusion: High YKL-40 levels appear to be associated with stroke.

Serum YKL-40 levels and disease characteristics in patients with rheumatoid arthritis.

Background:The present study aimed to evaluate serum YKL-40 levels in patients with rheumatoid arthritis (RA) compared to healthy subjects and to search whether there is an association between YKL-40 levels and disease characteristics in RA.Methods:In this cross-sectional study, 60 RA patients based on the ACR/EULAR 2010 criteria and 30 age- and sex-matched healthy controls were included. In patients, clinical examination was performed and disease activity score 28 (DAS-28) measure of disease activity was assessed. Serum YKL-40 level was measured using ELISA kit.Results:The mean±SD age of patients and controls was 54.86±11.65 and 50.71±3.72 years, respectively). Serum YKL-40 level was significantly higher in RA patients (951.63±639.98 pg/mL) compared to healthy controls (444.92±150.37 pg/mL) (P<0.001). There was no significant difference in serum YKL-40 level according to the activity of disease (p>0.05). There were significant positive correlations between serum YKL-40 level with disease activity (r=0.347, P=0.007) and rheumatoid factor (r=0.396, P=0.002). There were no significant correlations between serum YKL-40 level with demographic characteristics as well as biochemical measurements including serum creatinine, blood urea nitrogen, erythrocyte sedimentation rate, C-reactive protein and anti-cyclic citrullinated peptide.Conclusion:Our study revealed higher serum YKL-40 levels in RA patients compared to healthy controls, which correlated positively with disease activity. Therefore, YKL-40 can be considered as a novel biomarker for disease activity estimation in RA.

Elevation of YKL-40 in the CSF of Anti-NMDAR Encephalitis Patients Is Associated With Poor Prognosis.

Objective: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis predominantly affects children and young women; the disease can have a multistage presentation and exhibit a wide variety of neuropsychiatric features. This study aimed to investigate the profile of YKL-40 (Chitinase 3-like 1) in anti-NMDAR encephalitis patients and evaluate its association with modified Rankin Scale (mRS) scores and expression of inflammatory cytokines.Methods: A total of 66 patients were enrolled in this study, 33 with anti-NMDAR encephalitis, 13 with viral meningitis and 20 with non-inflammatory neurological disease. Patients were evaluated to determine mRS scores at disease onset and at the 3 month follow-up; cerebrospinal fluid (CSF) samples were collected in the meantime. CSF levels of YKL-40 and cytokines (TNF-α, IL-6, IL-10) were measured by enzyme-linked immunosorbent assay.Results: CSF levels of YKL-40 and inflammatory cytokines (TNF-α, IL-6, IL-10) were all more highly elevated in patients with anti-NMDAR encephalitis at the acute stage of disease compared with the controls. Levels of CSF YKL-40 were correlated with levels of IL-6 both at disease onset and at the 3 month follow-up. Changes in YKL-40 levels were significantly correlated with improved mRS scores in patients with anti-NMDAR encephalitis.Conclusion: Our study suggests that CSF levels of YKL-40 in patients with anti-NMDAR encephalitis were increased and correlated with clinical mRS scores. This may be reflective of the underlying neuroinflammatory process. YKL-40 demonstrates potential as a possible biomarker for the prognosis of anti-NMDAR encephalitis.

YKL-40 in the diagnosis, prediction of prognosis, and platinum sensitivity in serous epithelial ovarian cancer.

Objective:To evaluate the use of YKL-40 in the discrimination between benign and malignant adnexal mass and to determine its prognostic value in assessing residual tumor after primary cytoreduction and platinum sensitivity in serous epithelial ovarian carcinoma (EOC). Materials and Methods:During the three years from January 2015 to December 2017, a nonconsecutive series of 100 patient (60 malignant, 40 benign) who underwent surgery for an adnexal mass were enrolled in the study. Preoperatively, serum samples were collected for YKL-40 level analysis.Results:YKL-40 [receiver operator characteristics (ROC)-area under curve (AUC)=0.83] was a significantly better predictor of EOC than cancer antigen-125 (ROC-AUC=0.75). Using a cut-off for YKL-40 of 47.7 ng/mL had a sensitivity of 80% and a specificity of 70%. Higher serum YKL-40 levels were associated with advanced stage, higher grade, residual tumor after primary cytoreduction and recurrence. Platinum-sensitive patients had significantly elevated levels of YKL-40 compared with platinum-resistant or refractory patients.Conclusion:The results obtained from our study support the use of serum YKL-40 for the discrimination between malignant and benign ovarian tumors. YKL-40 levels in patients with serous EOC may also predict disease residual disease after primary cytoreduction and recurrence. Further studies are needed to understand the relationship between YKL-40 and platinum sensitivity.

The YKL-40 protein is a potential biomarker for COPD: a meta-analysis and systematic review.

BackgroundMany studies have found that YKL-40 may play an important pathogenic role in COPD. However, the results of these studies were inconsistent. Therefore, we performed a systematic review and meta-analysis to investigate the role of YKL-40 in COPD.MethodsWe performed a systematic literature search in many database and commercial internet search engines to identify studies involving the role of YKL-40 in patients with COPD. The standardized mean difference (SMD) and Fisher’s Z-value with its 95% confidence interval (CI) were used to investigate the effect sizes.ResultsA total of 15 eligible articles including 16 case–control/cohort groups were included in the meta-analysis. The results indicated that the serum YKL-40 levels in patients with COPD were significantly higher than those in healthy controls (SMD =1.58, 95% CI =0.68–2.49, P=0.001), and it was correlated with lung function (pooled r=−0.32; Z=−0.33; P<0.001). The results of subgroup analysis found that the serum YKL-40 levels were statistically different between the exacerbation group and the stable group in patients with COPD (SMD =1.55, 95% CI =0.81–2.30, P<0.001). Moreover, the results indicated that the sputum YKL-40 levels in patients with COPD were also significantly higher than those in healthy controls (SMD =0.70, 95% CI =0.10–1.30, P=0.022).ConclusionThe current study suggests that YKL-40 may be implicated in bronchial inflammation and remodeling in COPD and may be considered as a useful biomarker for COPD diagnosis and monitoring.