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Abstract Background Cystinosis is an autosomal recessive lysosomal storage disorder caused by cystine crystals accumulation within lysosomes resulting in multi-organ dysfunction. Infantile nephropathic cystinosis is the most common phenotype of the disease. Cystinosis distal myopathy was first described in 1994 with a 24% prevalence in cystinosis adult patients. Methods We prospectively evaluated the clinical, biochemical, and radiological data of 22 nephropathic cystinosis pediatric patients from 19 unrelated families (17 males and 5 females, their ages 105.7 ± 41.5 months) recruited at the cystinosis clinic at Cairo University Children’s Hospital. Biochemical assessment included several inflammatory biomarkers, such as CRP, ESR, chitotriosidase, and galectin-3. We further performed conventional MRI for the muscles of both upper and lower limbs for potential detection of early myopathic involvement. We compared these findings with 44 CKD children as pathological controls and 22 healthy pediatric controls. Results Clinically, no evidence of neuromuscular involvement was detected in our cystinosis pediatric cohort. Chitotriosidase was elevated significantly in cystinosis patients compared to CKD controls. Regarding MRI, morphologically, there were no significant differences between the muscles of cystinosis patients and healthy controls. Conclusion A significantly higher chitotriosidase activity in cystinosis patients seems to better represent the overall disease burden and cannot be linked to neuromuscular involvement. MRI findings in muscles of the cystinosis cohort are not striking and indicate no early changes at a younger age. Follow-up and further studies for higher age groups are required to accurately elucidate the MRI’s role in assessing cystinosis myopathy.

Abstract Background The aim of our study was to investigate serum chitotriosidase level in tuberculosis patients, its relationship with microbiological and clinical parameters, and response to treatment. Materials and methods This longitudinal panel study included 149 patients with confirmed TB disease. Serum chitotriosidase activity was measured at the beginning and the end of treatment. Factors associated with chitotriosidase activity were explored using univariate and multivariable logistic regression analysis. Results Out of 149 study participants, 71(47.7%) were female. The mean age was 53.0 (SD = 18.2). Majority of cases were new 118(79.2), predominantly 145 (97.3%) having pulmonary tuberculosis. More than half of the patients were sputum smear positive 91 (61.1%) while culture positive in 146 (98%) of them. According to radiological findings, cavitary lesions were found in 92 (63.4%) patients. Anti TB treatment was associated with significant decrease in serum chitotriosidase level (

Background: Cystinosis is an autosomal recessive lysosomal storage disorder caused by cystine crystals accumulation within lysosomes resulting in multi-organ dysfunction. Infantile nephropathic cystinosis is the most common phenotype of the disease. Cystinosis distal myopathy was first described in 1994 with a 24% prevalence in cystinosis adult patients. Methods: We prospectively evaluated the clinical, biochemical, and radiological data of 22 nephropathic cystinosis pediatric patients from 19 unrelated families (17 males and 5 females, their ages 105.7 ± 41.5 months) recruited at the cystinosis clinic at Cairo University Children's Hospital. Biochemical assessment included several inflammatory biomarkers, such as CRP, ESR, chitotriosidase, and galectin-3. We further performed conventional MRI for the muscles of both upper and lower limbs for potential detection of early myopathic involvement. We compared these findings with 44 CKD children as pathological controls and 22 healthy pediatric controls. Results: Clinically, no evidence of neuromuscular involvement was detected in our cystinosis pediatric cohort. Chitotriosidase was elevated significantly in cystinosis patients compared to CKD controls. Regarding MRI, morphologically, there were no significant differences between the muscles of cystinosis patients and healthy controls. Conclusion: A significantly higher chitotriosidase activity in cystinosis patients seems to better represent the overall disease burden and cannot be linked to neuromuscular involvement. MRI findings in muscles of the cystinosis cohort are not striking and indicate no early changes at a younger age. Follow-up and further studies for higher age groups are required to accurately elucidate the MRI's role in assessing cystinosis myopathy. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to investigate serum chitotriosidase level in tuberculosis patients, its relationship with microbiological and clinical parameters, and response to treatment. Materials and methods: This longitudinal panel study included 149 patients with confirmed TB disease. Serum chitotriosidase activity was measured at the beginning and the end of treatment. Factors associated with chitotriosidase activity were explored using univariate and multivariable logistic regression analysis. Results: Out of 149 study participants, 71(47.7%) were female. The mean age was 53.0 (SD = 18.2). Majority of cases were new 118(79.2), predominantly 145 (97.3%) having pulmonary tuberculosis. More than half of the patients were sputum smear positive 91 (61.1%) while culture positive in 146 (98%) of them. According to radiological findings, cavitary lesions were found in 92 (63.4%) patients. Anti TB treatment was associated with significant decrease in serum chitotriosidase level (< 0.001). New TB treatment (OR = 4.41%;95% CI = 1.20–9.89), and cavitary lesions (OR = 3.86;95%CI = 0,59-26.57) were found to be significantly associated with decrease of chitotriosidase activity. Conclusions: The results of our study showed that serum chitotriosidase values are strong biomarkers for starting anti TB treatment and for treatment monitoring, since decrease in serum chitotriosidase level can predict favorable treatment response in patients with tuberculosis. Further studies are needed to explore these, and other factors associated with chitotriosidase activity among tuberculosis patients. [ABSTRACT FROM AUTHOR]

Leukodystrophies represent a large and complex group of inherited disorders affecting the white matter of the central nervous system. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare leukodystrophy which still needs the proper identification of diagnostic, prognostic, and monitoring biomarkers. The aim of this study was to determine the diagnostic and prognostic value of chitinases and neurofilament light chain as biomarkers for ALSP. A cross-sectional study was performed to analyze cerebrospinal fluid levels of chitinases (chitotriosidase and chitinase 3-like 2) and neurofilament light chain in five different groups: (i) normal health individuals; (ii) patients with definitive diagnosis of ALSP and genetic confirmation; (iii) asymptomatic patients with CSF1R variants; (iv) patients with other adult-onset leukodystrophies; and (v) patients with amyotrophic lateral sclerosis (external control group). Chitinase levels showed a statistical correlation with clinical assessment parameters in ALSP patients. Chitinase levels were also distinct between ALSP and the other leukodystrophies. Significant differences were noted in the levels of chitinases and neurofilament light chain comparing symptomatic (ALSP) and asymptomatic individuals with CSF1R variants. This study is the first to establish chitinases as a potential biomarker for ALSP and confirms neurofilament light chain as a good biomarker for primary microgliopathies.

Sarcoidosis is a granulomatous disease of unknown etiology that can affect almost any organ. Although the acute form can have spontaneous regression, a certain number of patients can have a chronic form, which leads to an increase in mortality and a decrease in the quality of life. Considering that the risk factors are still unknown, we wanted to compare the characteristics of patients with acute and chronic forms of sarcoidosis in Serbia in order to determine significant differences between them with hopes of contributing to everyday clinical practice. A total of 2380 patients treated in our clinic were enrolled in this study. They were separated into the following two groups: 1126 patients with acute form and 1254 patients with chronic form. They were further compared by gender, smoking status, radiological status, exposition, biomarkers for sarcoidosis, organ involvement, and other comorbidities; the distribution of patients according to regions of Serbia was also noted. Statistical significance was found in radiological findings (p < 0.001), biomarkers (calcium in 24 h urine p < 0.001; chitotriosidase p = 0.001), and the affliction of organs (p < 0.001). The differences noted in this paper could help improve our understanding of this disease. [ABSTRACT FROM AUTHOR]

Aim. To assess the relationship between plasma chitotiosidase (CHIT) level and mortality in hospitalized patients with COVID-19. Materials and methods. 347 hospitalized patients with COVID-19 were enrolled in our single-center cohort prospective observational study. On the first day of hospitalization the patients were assessed by the level of CHIT in the venosus blood to addition to default laboratory examinations. The primary endpoint was all-cause death. The survival after hospital discharge were assessed via phone calls on 90 and 180 days since inclusion to the study (NCT04752085). Results. Our study included 347 patients. The first symptoms appeared in 7 days [5; 7] before hospitalization; 283 (84.3%) patients had less than 50% of the involvement of the lung tissue to the inflammation process (CT 02); 36 (10.4%) patients had died since the start of our investigation; 30 (83.3%) of them died during hospitalization, others -no later than 60 days; 68 (19%) people didnt answer during phone call. The survivor's activity of the enzyme in the deceased was significantly lower in compare to deceased patients (90.5 [40.2; 178.0] nmol/h/mL vs 180.0 [77.2; 393.2] nmol/h/mL; p=0.001). Survivor of the patients with a higher level of the activity of the CHIT (more than 171 nmol/h/mL) was statically significantly lower. Conclusion. Rising of the CHIT's activity more than 171 nmol/h/mL might be an early independent predictor of the bad prognosis of the patients, who were hospitalized with COVID-19 infection.

The present study the enzyme chitotriosidase emerged as a biomarker that can distinguish silicosis from exposure and healthy controls. Changes in chitotriosidase, immune system, and oxidative stress mechanisms indicated early involvement of silica in the pulmonary system. Objective: We aimed to evaluate the enzyme activity of chitotriosidase as a biomarker in early diagnosis silicosis and to investigate immune system response and oxidative stress caused by silica exposure. Materials and Methods: Silicosis patients (n = 116), exposed to silica without disease (n = 76), and healthy individuals (n = 55) were included. Serum levels of chitotriosidase, proinflammatory cytokines, oxidant-antioxidant, and immune parameters were measured. Results: Serum chitotriosidase enzyme levels in the silicosis group were statistically significantly higher than the exposure and control groups. Inflammatory biomarkers and 8-hydroxy-2-deoxyguanosine levels were found to be statistically significantly higher in the silicosis and exposure group compared with the controls, while superoxide dismutase and glutathione peroxidase were lower. Conclusions: Increased serum chitotriosidase level emerged as a biomarker that can not only distinguish silicosis from exposure and healthy controls but also indicate early pulmonary effects of silica. [ABSTRACT FROM AUTHOR]

Chitotriosidase (CHIT), a mammalian chitinase secreted by neutrophils and activated macrophages, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. The aim of this study is to evaluate CHIT activity as an early biomarker of arterial stiffness in people with T2D free from overt vascular complications. In this cross-sectional study, arterial stiffness as measured using standard pulse wave velocity (PWV) was evaluated in 174 people with T2D without overt vascular disease. Then, we measured CHIT serum activity with an electrochemiluminescence assay in two subgroups of participants: 35 with the highest (high-PWV) and 40 with the lowest (low-PWV) PWV values. CHIT activity was no different between the low-PVW and high-PWV groups (12.7 [9.6–17.9] vs. 11.4 [8.8–15.0] nmol/mL/h, respectively). Compared with the low-PWV group, the high-PWV participants were older (p < 0.001); had a longer duration of diabetes (p = 0.03); higher ankle–brachial index ABI (p = 0.04), systolic blood pressure (p = 0.002), diastolic blood pressure (p = 0.005), fasting blood glucose (p = 0.008), and HbA1c (p = 0.005); and lower eGFR (p = 0.03) and body mass index (BMI) (p = 0.01). No association was present with sex, duration of diabetes, age, BMI, peripheral blood pressure, laboratory parameters, and glucose-lowering medications or ongoing antihypertensive therapy. Although no association was found, this study provides novel data about the association of CHIT activity with CVD, focusing on a specific outcome (arterial stiffness) in a well-defined population of subjects with T2D without established CVD. [ABSTRACT FROM AUTHOR]

A personalized treatment decision for Gaucher disease (GD) patients should be based on relevant markers that are specific to GD, play a direct role in GD pathophysiology, exhibit low genetic variation, reflect the therapy, and can be used for all patients. Thirty-four GD patients treated with enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) were analyzed for platelet count, chitotriosidase, and tartrate-resistant acid phosphatase activity in plasma samples, and quantitative measurement of Lyso-Gb1 was performed in dried blood spots. In our ERT and SRT study cohorts, plasma lyso-GL1 correlated significantly with chito-triosidase (ERT: r = 0.55, p < 0.001; SRT: r = 0.83, p < 0.001) and TRAP (ERT: r = 0.34, p < 0.001; SRT: r = 0.88, p < 0.001), irrespective of treatment method. A platelet count increase was associated with a Lyso-Gb1 decrease in both treatment groups (ERT: p = 0.021; SRT: p = 0.028). The association of Lyso-Gb1 with evaluated markers was stronger in the SRT cohort. Our results indicate that ERT and SRT in combination or in a switch manner could offer the potential of individual drug effectiveness for particular GD symptoms. Combination of the key biomarker of GD, Lyso-Gb1, with other biomarkers can offer improved response assessment to long-term therapy. [ABSTRACT FROM AUTHOR]

Background. The identification of early predictors of poor outcomes of new coronavirus infection is necessary for optimizing patient management algorithms for hospitalized patients with COVID-19. Aim. To study the role of chitotriosidase activity as a marker of unfavorable outcomes in COVID-19 hospitalized patients. Materials and methods. The prospective observational single-center study included 347 patients with COVID-19 hospitalized in university clinic. In addition to the standard laboratory analysis (complete blood count, C-reactive protein, ferritin, creatinine, international normalized ratio, etc.) the blood serum chitotriosidase activity was determined at all the patients on admission. Primary endpoints were mortality from all causes and performing invasive ventilation (IV) and/or non-invasive ventilation (NIV). This study was approved by the Local Ethics Committee №12-21 (Clinical Trial Registry: NCT04752085). Results. A total of 347 patients were enrolled in this study (average age 66 years, females 182 52.5%), 30 patients (8.6%) died during the hospitalization, 39 (11.2%) performed IV or NIV. Along with age more than 65 (odds ratio OR 10.81, 95% confidence interval CI 2.6444.22) and Neutrophil-Lymphocyte Ratio higher than 7 (OR 15.89, 95% CI 3.0981.65) chitotriosidase activity higher than 170 ng/hr/ml (OR 4.23, 95% CI 1.4512.35) were independent predictors of mortality during hospitalization. Neutrophil-Lymphocyte Ratio higher than 5.6 (OR 11.22, 95% CI 2.3753,1) and сhitotriosidase activity higher than 151 ng/hr/ml (OR 3.17, 95% CI 1.317.67) have been evaluated as predictors of performing IV/NIV. Conclusion. Chitotriosidase level more than 151 nmol/h/mL could be considered as an early predictor of severity and poor prognosis in hospitalized patients with COVID-19.

Several reports have pointed out that Chitinases are expressed and secreted by various cell types of central nervous system (CNS), including activated microglia and astrocytes. These cells play a key role in neuroinflammation and in the pathogenesis of many neurodegenerative disorders. Increased levels of Chitinases, in particular Chitotriosidase (CHIT-1) and chitinase-3-like protein 1 (CHI3L1), have been found increased in several neurodegenerative disorders. Although having important biological roles in inflammation, to date, the molecular mechanisms of Chitinase involvement in the pathogenesis of neurodegenerative disorders is not well-elucidated. Several studies showed that some Chitinases could be assumed as markers for diagnosis, prognosis, activity, and severity of a disease and therefore can be helpful in the choice of treatment. However, some studies showed controversial results. This review will discuss the potential of Chitinases in the pathogenesis of some neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, to understand their role as distinctive biomarkers of neuronal cell activity during neuroinflammatory processes. Knowledge of the role of Chitinases in neuronal cell activation could allow for the development of new methodologies for downregulating neuroinflammation and consequently for diminishing negative neurological disease outcomes. [ABSTRACT FROM AUTHOR]

Gastric cancer is the fifth type of neoplasia most frequently diagnosed and the fourth cause of death among other cancers. Prevalence is around two times higher for males than females. Chitotriosidase and neopterin are two molecular biomarkers with potential diagnostic and prognostic use in malignant pathology. We conducted a longitudinal prospective cohort study on thirty-nine patients with gastric adenocarcinoma, with a male-to-female ratio of 1.78 and an average age of 64.3 ± 9.97 years. No statistically significant differences in biomarker levels at presentation were observed between curative-intent surgery (28 patients) and advanced cases, suited only for palliative procedures (11 patients). Biomarker values were not significantly different for the advanced T stage and the presence of metastasis (p > 0.05—Mann Whitney test). The patients that died in the first 30 days after surgery did not present significantly different values at baseline, in comparison with those that had longer survival times, though a significant cut-off value was observed for chitotriosidase activity at 310 nmol/mL/h [AUC (area under the curve) = 0.78; 95% CI (0.61–0.92)]. The cut-off values corresponding to death after the first year, tumor invasion, and metastasis were not statistically significant. In the COX multivariate model, neopterin did not validate itself as a prognostic biomarker, however, chitotriosidase activity before surgery was significantly associated with overall survival (HR = 1.0038, p = 0.03). We conclude that chitotriosidase may have the potential to improve the prognostic model for gastric adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: β-thalassemia major and Niemann-Pick diseases have similar clinical and laboratory findings. We aimed to investigate the effects of sphingomyelin phosphodiesterase 1 (SMPD1) gene variants on the clinical and laboratory findings in patients with β-thalassemia major. Methods and results: This study included 45 patients who were followed up for β-thalassemia major in our clinic. Plasma chitotriosidase, leukocyte acid sphingomyelinase, liver enzymes, ferritin, hemogram, biochemical parameters, SMPD1 gene variant analysis, cardiac T2* MRI, and liver R2 MRI were assessed in all patients. The SMPD1 gene c.132_143del, p.A46_L49del (c.108GCTGGC[4] (p.38AL[4])) (rs3838786) variant was detected in 9 of 45 (20.0%) patients. Plasma chitotriosidase, ferritin, acetyl aminotransferase, and alanine aminotransferase levels were significantly higher in patients with the gene variant than in those without (p < 0.05). Leukocyte acid sphingomyelinase levels were significantly lower in patients with the gene variant than in those without (p < 0.05). Conclusion: These results imply that the clinical and laboratory findings and some features of disease progression in patients with β-thalassemia major are similar to those of Niemann-Pick disease. They also suggest that SMPD1 gene c.132_143del, p.A46_L49del (c.108GCTGGC[4] (p.38AL[4])) (rs3838786) variant may underlie these clinical findings in patients with β-thalassemia major. [ABSTRACT FROM AUTHOR]

Chitotriosidase is an enzyme produced and secreted in large amounts by activated macrophages, especially macrophages loaded with phagocytozed glycosphingolipid in Gaucher disease. Macrophages phagocytose decayed blood cells that contain a lot of sphingolipid-rich cell membranes. In Gaucher disease, due to a deficit in beta-glucocerebrosidase activity, the phagocytozed substrate glucocerebroside cannot undergo further catabolism. In such a situation, macrophages secrete chitotriosidase in proportion to the degree of overload. Gaucher disease (GD) is a recessively inherited disorder resulting in storage of glucosylceramide (GlcCer) in lysosomes of tissue macrophages. It is directly caused by the deficiency of beta-glucocerebrosidase (GBA) activity. Chitotriosidase has been measured systematically each year in the same group of 49 patients with type 1 and 3 GD for over 20 years. Our analysis showed that chitotriosidase is very sensitive biomarker to enzyme replacement therapy (ERT). The response to treatment introduction is of an almost immediate nature, lowering pathologically high chitotriosidase levels by a factor of 2 in a time scale of 8 months, on average. Long term enzyme replacement therapy (ERT) brings chitotriosidase activity close to reference values. Finally, reducing the dose of ERT quickly boosts chitotriosidase activity, but restoring the initial dose of treatment brings chitotriosidase level of activity back onto the decreasing time trajectory. [ABSTRACT FROM AUTHOR]

Chitotriosidase (CHIT1) is an enzyme produced by macrophages that regulates their differentiation and polarization. Lung macrophages have been implicated in asthma development; therefore, we asked whether pharmacological inhibition of macrophage-specific CHIT1 would have beneficial effects in asthma, as it has been shown previously in other lung disorders. CHIT1 expression was evaluated in the lung tissues of deceased individuals with severe, uncontrolled, steroid-naïve asthma. OATD-01, a chitinase inhibitor, was tested in a 7-week-long house dust mite (HDM) murine model of chronic asthma characterized by accumulation of CHIT1-expressing macrophages. CHIT1 is a dominant chitinase activated in fibrotic areas of the lungs of individuals with fatal asthma. OATD-01 given in a therapeutic treatment regimen inhibited both inflammatory and airway remodeling features of asthma in the HDM model. These changes were accompanied by a significant and dose-dependent decrease in chitinolytic activity in BAL fluid and plasma, confirming in vivo target engagement. Both IL-13 expression and TGFβ1 levels in BAL fluid were decreased and a significant reduction in subepithelial airway fibrosis and airway wall thickness was observed. These results suggest that pharmacological chitinase inhibition offers protection against the development of fibrotic airway remodeling in severe asthma. [ABSTRACT FROM AUTHOR]

Chronic inflammation is demonstrated to play a direct role in carcinogenesis. Our exploratory study aimed to assess the potential added value of two inflammation biomarkers, chitotriosidase and neopterin, in follow-up evaluation of patients with colorectal cancer (CRC). An observational exploratory study was conducted. Patients with CRC and matched controls (1:1, age, sex, and living environment) were evaluated. The patients with CRC (CRC group) and controls were assessed at baseline (before surgical intervention for patients with CRC). Patients with CRC were also evaluated at 1-year follow-up. Significantly more patients with blood group A (54.5% vs. 25.0%) and smokers (50.0% vs. 22.7%) were in the CRC group. The serum values of chitotriosidase and neopterin were higher in CRC patients than in controls, but only neopterin reached the conventional level of statistical significance (p-value = 0.015). The circulating chitotriosidase and neopterin values decreased significantly at 1-year follow-up (p-value < 0.0001). Patients with higher N- and M-stage showed statistically significant higher levels of chitotriosidase and neopterin at baseline and 1-year follow-up (p-values < 0.03). Circulating chitotriosidase levels also showed statistically significant differences regarding baseline and 1-year follow-up on patients with CRC and different differentiation grades (p-values < 0.02). The circulating levels of neopterin significantly decreased at 1-year follow-up, indicating its potential as a prognostic marker. The circulating values of chitotriosidase and neopterin exhibit significant differences in patients with than without recurrences. Our results support further evaluation of chitotriosidase and neopterin as prognostic markers in patients with CRC. [ABSTRACT FROM AUTHOR]

Gallstones are a common surgical pathology. Laparoscopic cholecystectomy represents the elective treatment. Complicated cases can increase the rate of conversion, the duration, and the difficulty of the intervention, along with the hospitalization period. A prospective cohort study was conducted on 51 patients with gallstones. Only subjects with normal renal, pancreatic, and hepatic functions were included. The severity of cholecystitis was evaluated by considering the ultrasound examination, intraoperative findings, and pathology report. We evaluated two potential biomarkers, namely neopterin and chitotriosidase, by comparing their levels before and after the intervention for chronic (n = 36) and complicated (n = 15) cases, as well as their eventual association with the hospitalization period. Subjects with complicated cholecystitis had significantly higher (p = 0.01) neopterin levels at presentation (16.82 nmol/L vs. 11.92 nmol/L, median values), but the differences in chitotriosidase activity between complicated (170.00 nmol/mL/h) and chronic (160.00 nmol/mL/h) cases were not significant (p = 0.66). Patients with neopterin levels above the cut-off value 14.69 nmol/L had a 3.34 times higher risk of complicated cholecystitis. Twenty-four hours after the laparoscopic cholecystectomy, the differences in neopterin level and chitotriosidase activity between chronic and complicated cases were not significant. A significant decrease in chitotriosidase activity was observed after the intervention, only for complicated cases (190 nmol/mL/h vs. 145 nmol/mL/h, p = 0.007); for neopterin, the postoperative decrease was not statistically significant (19.42 nmol/L vs. 10.92 nmol/L, p = 0.06). No significant association with the hospitalization period was observed. Neopterin may be a useful biomarker for complicated cholecystitis, and chitotriosidase may have prognostic utility in early patient follow-up. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common form of progressively disabling dementia. The chitinases CHI3L1 and CHI3L2 have long been known as biomarkers for microglial and astrocytic activation in neurodegeneration. Here, we collected microarray datasets from the National Center for Biotechnology Information (NCBI) brain samples of non-demented controls (NDC) (n = 460), and of deceased patients with AD (n = 697). The AD patients were stratified according to sex. Comparing the high CHI3L1 and CHI3L2 expression group (75th percentile), and low CHI3L1 and CHI3L2 expression group (25th percentile), we obtained eight signatures according to the sex of patients and performed a genomic deconvolution analysis using neuroimmune signatures (NIS) belonging to twelve cell populations. Expression analysis revealed significantly higher CHI3L1 and CHI3L2 expression in AD compared with NDC, and positive correlations of these genes with GFAP and TMEM119. Furthermore, deconvolution analysis revealed that CHI3L1 and CHI3L2 high expression was associated with inflammatory signatures in both sexes. Neuronal activation profiles were significantly activated in AD patients with low CHI3L1 and CHI3L2 expression levels. Furthermore, gene ontology analysis of common genes regulated by the two chitinases unveiled immune response as a main biological process. Finally, microglia NIS significantly correlated with CHI3L2 expression levels and were more than 98% similar to microglia NIS determined by CHI3L1. According to our results, high levels of CHI3L1 and CHI3L2 in the brains of AD patients are associated with inflammatory transcriptomic signatures. The high correlation between CHI3L1 and CHI3L2 suggests strong co-regulation. [ABSTRACT FROM AUTHOR]

Objectives: Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease. The aim of our study was to investigate a possible role of chitotriosidase (Chito) activity as a potential marker of inflammation in diagnosis of patients with HT. In addition, we aimed to determine the levels of inflammation markers such as YKL-40, high sensitivity C-reactive protein (hsCRP) and oxidative stress (OS) parameters such as thiobarbituric acid reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD), GSH-Px to evaluate an association between those inflammatory and OS markers in patients with HT. Methods: 42 patients with HT and 28 control cases were studied. All cases were euthyroid. Chito activity was measured fluorometrically based on Hollak et al's. method. hsCRP and YKL-40 levels were measured using ELISA. TBARS, SOD, and CAT activities were determined in hemolyzates. GSH-Px activity was determined by a colorimetric assay. Results: Higher Chito concentrations were observed in patients with HT compared to the control group (p=0.002). YKL-40 levels were detected higher in HT but it was not statistically significant (p=0.810). Chito levels were positively correlated with age and negatively correlated with SOD (r=0.360, p=0.021; r=-0.368, p=0.018). YKL-40 levels were positively correlated with FT3 and SOD in HT (r=0.324, p=0.037; r=0.312, p=0.044) and negatively correlated with age (r=-0.463, p=0.002). SOD levels were negatively correlated with age and positively correlated with YKL-40 (r=-0.371, p=0.016, r=0.312, p=0.044). Conclusion: We revealed that Chito levels were higher among euthyroid HT patients. This result may point out that Chito levels could be used as a potential marker of inflammation in HT. [ABSTRACT FROM AUTHOR]

Chitin, one of the most abundant biopolymers on Earth, is bound and degraded by chitinases, specialized enzymes that are similarly widespread in nature. Chitin catabolism affects global carbon and nitrogen cycles through a host of diverse biological processes, but recent work has focused attention on systems of chitin recognition and degradation conserved in mammals, connecting an ancient pathway of polysaccharide processing to human diseases influenced by persistent immune triggering. Here we review current advances in our understanding of how chitin-chitinase interactions affect mucosal immune feedback mechanisms essential to maintaining homeostasis and organ health.

Historically, disease burden and treatment responses in patients with Gaucher disease (GD) was assessed by monitoring clinical data, laboratory, imaging, chitotriosidase (CHITO), and other biomarkers; however, these biomarkers lack specificity and CHITO is uninformative in patients heterozygous or homozygous for the CHIT1 c.1049_1072dup24 variant. Recently, glucosylsphingosine (lyso-Gb1), a sensitive and specific GD biomarker, has been recommended for patient monitoring. Furthermore, studies measuring lyso-Gb1 and CHITO in patients on long-term treatment with enzyme replacement therapy (ERT) and/or substrate reduction therapy (SRT) reported as group data show a reduction in both analytes, yet individualized patient data are generally unavailable. We describe seven patients on long-term treatment with longitudinal clinical data with monitoring based on current treatment guidelines. We present four patients who exhibit stable disease with normalized CHITO despite elevated lyso-Gb1. We present one patient who transitioned from ERT to SRT due to lack of a clinical response with life-threatening thrombocytopenia who responded with marked improvement in platelets, and normalized levels of both CHITO and lyso-Gb1. Finally, we present two ERT to SRT switch patients with stable disease on ERT who exhibited non-compliance on SRT, one with mirrored marked elevations of CHITO and lyso-Gb1; and another with normal CHITO and platelets, but increasing lyso-Gb1 levels and enlarged spleen. These clinical vignettes highlight the role of lyso-Gb1 as a sensitive biomarker in management of patients with GD, and its further value when CHITO is normal and thus uninformative. We highlight the personalized medicine approach needed to optimize treatment outcomes and recommendations for these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: In patients with lung cancer, serum levels of neuron specific enolase were significantly decreased after the first chemotherapy cycle compared to pre-treatment values. In addition, the post-treatment values of neopterin were lower as well, but with marginal statistical significance. Conversely, circulating levels of chitotriosidase, squamous cell carcinoma antigen, vitamin D, and vitamin D receptor were not significantly modified in response to the first chemotherapy cycle. Background: We aimed to investigate the changes of inflammatory status reflected by serum levels of chitotriosidase (CHT) and neopterin, and how specific tumor markers such as neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCCA), as well as vitamin D metabolism assessed by vitamin D receptor (VDR) and 25-hydroxy vitamin D3 (25OHD3), were modified after the first cycle of chemotherapy in patients with lung cancer. Methods: We performed this first pilot study on twenty patients diagnosed with lung cancer by investigating the serum concentrations of CHT, neopterin, NSE, SCCA, VDR and 25OHD3 before and after the first cycle of chemotherapy. Results: The post-treatment values of NSE were significantly lower compared to the pre-treatment levels (14.37 vs. 17.10 ng/mL, p = 0.031). We noticed a similar trend in neopterin levels, but the difference was only marginally significant (1.44 vs. 1.17 ng/mL, p = 0.069). On the contrary, the variations of circulating SCCA, CHT, neopterin, VDR and 25OHD3, before and after treatment, did not reach statistical significance. Conclusion: Only circulating NSE was treatment responsive to the first chemotherapy cycle in patients with lung cancer, while inflammatory markers and vitamin D status were not significantly modified. [ABSTRACT FROM AUTHOR]

Objective:In this study, we aimed to investigate serum chitotriosidase (ChT) activity and irisin levels in children with obesity and compare them to those of healthy counterparts. Material and Methods: A total of 91 obese and 83 normal-weight children were included in the study. Serum ChT activity and irisin levels of children with obesity were compared to those of normal-weight children. Results: The mean ChT value in the obese group was 1825.332 ± 4804.147 nmol/L/h and was significantly higher than that in the control group. In contrast, the mean irisin level, 2679.663 ± 5473.58 pg/ml, was lower than that in the control group. The cutoff point of the continuous variable selected in the model for ChT was 601, with 31.9% sensitivity, 90.6% specificity, and an area under the curve of 0.596. The cutoff point for irisin was 901.4, with 83.5% sensitivity, 42.4% specificity, and an area under the curve of 0.617. Conclusion: This study is the first to show decreased serum both serum ChT activity and irisin level and ChT’s association with irisin levels in children with obesity . We argue that ChT and irisin should be considered potential biomarkers of metabolic syndrome in children with obesity.

Gaucher disease (GD) is a lysosomal storage disorder with glucocerebroside accumulation in the macrophages. The disease is divided into three types based on neurocognitive involvement with GD1 having no involvement while the acute (GD2) and chronic (GD3) are neuronopathic. The non-neurological symptoms of GD3 are well treated with enzyme replacement therapy (ERT) which has replaced hematopoietic stem cell transplantation (HSCT). ERT is unable to prevent neurological progression as the enzyme cannot cross the blood-brain barrier. In this retrospective study, we report the general, neurocognitive, and biochemical outcomes of three siblings with GD3 after treatment with ERT or HSCT. Two were treated with HSCT (named HSCT1 and HSCT2) and one with ERT (ERT1). All patients were homozygous for the c.1448 T > C, (p.Leu483Pro) variant in the GBA1 gene associated with GD3. ERT1 experienced neurocognitive progression with development of seizures, oculomotor apraxia, perceptive hearing loss and mental retardation. HSCT1 had no neurological manifestations, while HSCT2 developed perceptive hearing loss and low IQ. Chitotriosidase concentrations were normal in plasma and cerebrospinal fluid (CSF) for HSCT1 and HSCT2, but both were markedly elevated in ERT1. We report a better neurological outcome and a normalization of chitotriosidase in the two siblings treated with HSCT compared to the ERT-treated sibling. With the advancements in HSCT over the past 25 years, we may reconsider using HSCT in GD3 to achieve a better neurological outcome and limit disease progression. [ABSTRACT FROM AUTHOR]

Gastric cancer is the fifth type of neoplasia most frequently diagnosed and the fourth cause of death among other cancers. Prevalence is around two times higher for males than females. Chitotriosidase and neopterin are two molecular biomarkers with potential diagnostic and prognostic use in malignant pathology. We conducted a longitudinal prospective cohort study on thirty-nine patients with gastric adenocarcinoma, with a male-to-female ratio of 1.78 and an average age of 64.3 ± 9.97 years. No statistically significant differences in biomarker levels at presentation were observed between curative-intent surgery (28 patients) and advanced cases, suited only for palliative procedures (11 patients). Biomarker values were not significantly different for the advanced T stage and the presence of metastasis (p > 0.05—Mann Whitney test). The patients that died in the first 30 days after surgery did not present significantly different values at baseline, in comparison with those that had longer survival times, though a significant cut-off value was observed for chitotriosidase activity at 310 nmol/mL/h [AUC (area under the curve) = 0.78; 95% CI (0.61–0.92)]. The cut-off values corresponding to death after the first year, tumor invasion, and metastasis were not statistically significant. In the COX multivariate model, neopterin did not validate itself as a prognostic biomarker, however, chitotriosidase activity before surgery was significantly associated with overall survival (HR = 1.0038, p = 0.03). We conclude that chitotriosidase may have the potential to improve the prognostic model for gastric adenocarcinoma.

Ophidiomycosis, caused by the fungus Ophidiomyces ophidiicola, poses a threat to the health of wild and managed snakes worldwide. Variation in snake innate immunity, the primary defense against infection in reptiles, may explain the observed variation in ophidiomycosis clinical disease severity among snakes. In this study, two components of the innate immune response were examined in snake plasma. We investigated whether complement activity, as measured by sheep red blood cell hemolysis, and chitotriosidase activity were associated with ophidiomycosis disease severity and time in captivity in Lake Erie watersnakes (Nerodia sipedon insularum). There was no difference in complement-mediated hemolysis or chitotriosidase activities between snakes with varying levels of ophidiomycosis clinical severity sampled in the field. However, among snakes with skin lesions kept in captivity, chitotriosidase activity was significantly higher in snakes with mild disease, compared with snakes with severe disease, and hemolysis activity increased with time in captivity. Overall, Lake Erie watersnakes had higher complement activity, but lower chitotriosidase activity, compared with other reptile species. To our knowledge, this study is the first to describe chitotriosidase activity in a snake species. These results provide mixed evidence of associations between innate immune function and ophidiomycosis severity, and more work is needed to investigate differences among snake species. [ABSTRACT FROM AUTHOR]

Db/db mice (carrying a mutation in the gene encoding leptin receptor) show autophagy suppression. Our aim was to evaluate the effect of autophagy inducer trehalose on liver and heart autophagy in db/db mice and to study inflammation dysregulation and the suitability of chitinases' expression levels as diabetes markers. Thirty-eight male db/db mice and C57/BL mice (control) were used. The db/db model manifested inflammation symptoms: overexpression of TNF-α in the spleen and underexpression of IL-10 in the liver and spleen (cytokine imbalance). Simultaneously, we revealed decreased expression of chitotriosidase (CHIT1) and acid mammalian chitinase (CHIA) in the liver of db/db mice. CHIA expression in db/db mice is significantly lower only in the spleen. Trehalose treatment significantly reduced blood glucose concentration and glycated hemoglobin. Treatment of db/db mice by trehalose was followed by increased autophagy induction in the heart and liver (increased autolysosomes volume density studied by morphometric electron-microscopic method). Trehalose exerted beneficial cardiac effects possibly via increased lipophagy (uptake of lipid droplets). The autophagy activation by trehalose had several positive effects on the heart and liver of db/db mice; therefore, lipophagy activation seems to be a promising therapy for diabetes. [ABSTRACT FROM AUTHOR]

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

Abstract Background Cerebrospinal fluid from amyotrophic lateral sclerosis patients (ALS-CSF) induces neurodegenerative changes in motor neurons and gliosis in sporadic ALS models. Search for identification of toxic factor(s) in CSF revealed an enhancement in the level and enzyme activity of chitotriosidase (CHIT-1). Here, we have investigated its upregulation in a large cohort of samples and more importantly its role in ALS pathogenesis in a rat model. Methods CHIT-1 level in CSF samples from ALS (n = 158), non-ALS (n = 12) and normal (n = 48) subjects were measured using ELISA. Enzyme activity was also assessed (ALS, n = 56; non-ALS, n = 10 and normal-CSF, n = 45). Recombinant CHIT-1 was intrathecally injected into Wistar rat neonates. Lumbar spinal cord sections were stained for Iba1, glial fibrillary acidic protein and choline acetyl transferase to identify microglia, astrocytes and motor neurons respectively after 48 h of injection. Levels of tumour necrosis factor-α and interleukin-6 were measured by ELISA. Findings CHIT-1 level in ALS-CSF samples was increased by 20-fold and it can distinguish ALS patients with a sensitivity of 87% and specificity of 83.3% at a cut off level of 1405.43 pg/ml. Enzyme activity of CHIT-1 was also 15-fold higher in ALS-CSF and has a sensitivity of 80.4% and specificity of 80% at cut off value of 0.1077989 μmol/μl/min. Combining CHIT-1 level and activity together gave a positive predictive value of 97.78% and negative predictive value of 100%. Administration of CHIT-1 increased microglial numbers and astrogliosis in the ventral horn with a concomitant increase in the levels of pro-inflammatory cytokines. Amoeboid-shaped microglial and astroglial cells were also present around the central canal. CHIT-1 administration also resulted in the reduction of motor neurons. Conclusions CHIT-1, an early diagnostic biomarker of sporadic ALS, activates glia priming them to attain a toxic phenotype resulting in neuroinflammation leading to motor neuronal death.

Natalia Przysucha, Katarzyna Górska, Rafal Krenke Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, Warsaw, PolandCorrespondence: Katarzyna GórskaDepartment of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, Banacha 1A, Warsaw 02-097 Email drkpgorska@gmail.comAbstract: Chitinases, enzymes that cleave chitin’s chain to low molecular weight chitooligomers, are widely distributed in nature. Mammalian chitinases belong to the 18-glycosyl-hydrolase family and can be divided into two groups: true chitinases with enzymatic activity (AMCase and chitotriosidase) and chitinase-like proteins (CLPs) molecules which can bind to chitin or chitooligosaccharides but lack enzymatic activity (eg, YKL-40). Chitinases are thought to be part of an innate immunity against chitin-containing parasites and fungal infections. Both groups of these hydrolases are lately evaluated also as chemical mediators or biomarkers involved in airway inflammation and fibrosis. The aim of this article is to present the current knowledge on the potential role of human chitinases and CLPs in the pathogenesis, diagnosis, and course of obstructive lung diseases. We also assessed the potential role of chitinase and CLPs inhibitors as therapeutic targets in chronic obstructive pulmonary disease and asthma.Keywords: asthma, COPD, YKL-40, CHIT1, chitotriosidase, AMCase

Abstract Background Serum chitotriosidase is a promising biomarker that has shown high specificity and sensitivity in patients with sarcoidosis. The aim of this study was to investigate correlations between serum chitotriosidase, clinical phenotypes, disease localizations and different radiological lung involvement and to identify clinical features associated with over-expression of chitotriosidase in a large cohort of sarcoidosis patients. Methods Chitotriosidase activity was evaluated in a population of 694 consecutive patients (males 39%, age 55.8 ± 12.8 years). Clinical and respiratory functional characteristics, Clinical Outcome Scale (COS) classification, clinical phenotypes proposed by the GenPhenResA project, and radiological assessment, including CT scan, were collected. Serum sampling and clinical and functional assessments at follow-up were also included. Results Significantly higher chitotriosidase activity was observed in sarcoidosis patients than in healthy controls (p

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

Chronic inflammation is demonstrated to play a direct role in carcinogenesis. Our exploratory study aimed to assess the potential added value of two inflammation biomarkers, chitotriosidase and neopterin, in follow-up evaluation of patients with colorectal cancer (CRC). An observational exploratory study was conducted. Patients with CRC and matched controls (1:1, age, sex, and living environment) were evaluated. The patients with CRC (CRC group) and controls were assessed at baseline (before surgical intervention for patients with CRC). Patients with CRC were also evaluated at 1-year follow-up. Significantly more patients with blood group A (54.5% vs. 25.0%) and smokers (50.0% vs. 22.7%) were in the CRC group. The serum values of chitotriosidase and neopterin were higher in CRC patients than in controls, but only neopterin reached the conventional level of statistical significance (p-value = 0.015). The circulating chitotriosidase and neopterin values decreased significantly at 1-year follow-up (p-value < 0.0001). Patients with higher N- and M-stage showed statistically significant higher levels of chitotriosidase and neopterin at baseline and 1-year follow-up (p-values < 0.03). Circulating chitotriosidase levels also showed statistically significant differences regarding baseline and 1-year follow-up on patients with CRC and different differentiation grades (p-values < 0.02). The circulating levels of neopterin significantly decreased at 1-year follow-up, indicating its potential as a prognostic marker. The circulating values of chitotriosidase and neopterin exhibit significant differences in patients with than without recurrences. Our results support further evaluation of chitotriosidase and neopterin as prognostic markers in patients with CRC.

Chitotriosidase is an enzyme produced and secreted in large amounts by activated macrophages, especially macrophages loaded with phagocytozed glycosphingolipid in Gaucher disease. Macrophages phagocytose decayed blood cells that contain a lot of sphingolipid-rich cell membranes. In Gaucher disease, due to a deficit in beta-glucocerebrosidase activity, the phagocytozed substrate glucocerebroside cannot undergo further catabolism. In such a situation, macrophages secrete chitotriosidase in proportion to the degree of overload. Gaucher disease (GD) is a recessively inherited disorder resulting in storage of glucosylceramide (GlcCer) in lysosomes of tissue macrophages. It is directly caused by the deficiency of beta-glucocerebrosidase (GBA) activity. Chitotriosidase has been measured systematically each year in the same group of 49 patients with type 1 and 3 GD for over 20 years. Our analysis showed that chitotriosidase is very sensitive biomarker to enzyme replacement therapy (ERT). The response to treatment introduction is of an almost immediate nature, lowering pathologically high chitotriosidase levels by a factor of 2 in a time scale of 8 months, on average. Long term enzyme replacement therapy (ERT) brings chitotriosidase activity close to reference values. Finally, reducing the dose of ERT quickly boosts chitotriosidase activity, but restoring the initial dose of treatment brings chitotriosidase level of activity back onto the decreasing time trajectory.

• CHIT1 regulates brain inflammation via HDAC3/NF-κB p65 pathway, contributing to improvement of cognitive impairment. • CHIT1 skews polarization from a pro-inflammatory environment toward an anti-inflammatory one. • CHIT1 has a potential therapeutic value in AD via modulation of inflammation. Chitotriosidase (CHIT1, chitinase 1) is increased in the cerebrospinal fluid and peripheral blood of Alzheimer's disease (AD) patients. Our previous study has shown that CHIT1 provides potential protection through microglial polarization and reduction of β-amyloid (Aβ) oligomers on rat models of AD. Histone deacetylase 3 (HDAC3) plays a significant role in the expression and regulation of proteins related to the pathophysiology of AD. In addition, nuclear factor-kappa B (NF-κB) signaling pathway activation in neurons is associated with the progression of AD. NF-κB activation is regulated by HDAC3 deacetylation. In the present study, we researched the role of CHIT1 in HDAC3/NF-κB signaling in D-galactose (D-gal) and aluminum-exposed rat model with cognitive impairments. Following CHIT1 treatment, we found that the protein and mRNA levels of HDAC3 and NF-κB were reduced, the expression level of IκBα increased, anti-inflammatory factors (Arg-1, IL-10, and CD206) were elevated while pro-inflammatory factors (TNF-a, iNOS, and IL-1β) were decreased in D-gal/aluminum-induced AD rats. These results indicate that CHIT1 can regulate brain inflammation via HDAC3/NF-κB p65 pathway, contributing to improvement of cognitive impairment. [ABSTRACT FROM AUTHOR]

Background/aim: Chitotriosidase and YKL-40, also called chitinase 3-like protein 1, are homologs of family 18 glycosyl hydrolases, secreted by human macrophages and granulocytes under inflammatory conditions. Although increased levels of chitotriosidase and YKL-40 are linked with several inflammatory diseases, the physiological utility of these two enzymes is still not fully characterized. This study aims to analyse the serum YKL-40 and chitotriosidase levels of acute pancreatitis patients to assess whether their activity correlates with acute pancreatitis and its severity. Materials and methods: Chitotriosidase and YKL-40 levels, along with routine laboratory parameters, were determined from the serum samples of 41 acute pancreatitis patients, at both onset and remission (male/female: 22/19), and 39 healthy subjects (male/female: 19/20). The Modified Glasgow Prognostic Score was used to predict the severity of the disease, and a correlation analysis was performed between study variables. Results: A statistically significant increase in both chitotriosidase and YKL-40 levels was observed in acute pancreatitis patients compared to healthy controls (P < 0.001). Higher levels of YKL-40, chitotriosidase and C-reactive protein were found in patients with acute pancreatitis at onset than in remission. The correlation analysis showed a statistically significant association between YKL-40 and chitotriosidase (p = 0.039, r = 0.323). The cut-off point for YKL-40, for detecting acute pancreatitis, was 60.3 with a sensitivity and specificity of 84.9% and 84.6% (AUC: 0.890). The optimum cut-off points for chitotriosidase, for detecting acute pancreatitis, was 33.5 with a sensitivity and specificity of 79.5% and 78.4% (AUC: 0.899). Conclusion: Elevated YKL-40 and chitotriosidase levels in acute pancreatitis patients demonstrate the importance of possible macrophage involvement in the pancreatic microenvironment during acute pancreatitis progression. [ABSTRACT FROM AUTHOR]

Background/aim: Chitotriosidase (ChT) is an enzyme secreted by activated macrophages and neutrophils in response to proinflammatory signals. There is growing evidence indicating that ChT activity reflects the systemic inflammatory status. This study aimed to investigate whether serum ChT activity increased in patients with psoriasis and related comorbidities. Materials and methods: This cross-sectional study included 53 (28 with associated comorbidities and 25 without comorbidities) patients with psoriasis and 52 healthy volunteers. All participants underwent laboratory investigations for serum ChT levels, complete blood count, erythrocyte sedimentation rate, C-reactive protein, and serum lipid levels. Results: The patients with psoriasis showed significantly higher levels of ChT activity as compared to the healthy controls (23.5 ± 11.4 vs. 17.5 ± 10.4 μmol/mL/hour; p = 0.015). Additionally, the ChT activity was significantly higher in patients with comorbidities than in those without (p = 0.042). Conclusion: Our data support the pathogenetic role of inflammatory processes induced by macrophage activation in patients with psoriasis and related comorbidities. We believe that high ChT activity in patients with psoriasis may serve as an early prediction of the possible related comorbidities. [ABSTRACT FROM AUTHOR]

Objective β-thalassemia major (β-TM) is an autosomalrecessive condition with various clinical presentations, including anemia, splenomegaly, and skeletal and cardiac involvement. The aim of this study was to analyze leukocyte β-glucocerebrosidase (β-GBA) levels and plasma chitotriosidase (PCT) activity in patients with β-TM and to determine the significance of these two enzymes in this disease. Patients and methods This study included 40 patients, 18–55 years of age, who were under follow-up for β-TM in our clinic. Physical examination, ECG, echocardiography, laboratory findings, and the results of imaging tests obtained during routine control visits were recorded. Leukocyte β-GBA and PCT activity levels were analyzed in the blood using fluorometric methods. Results The average age of the 40 patients, which included 24 (60%) women and 16 (40%) men, was 28.5±7.8 years. Leukocyte β-GBA levels were below 2.5 nmol/mg/h in 15 patients, and PCT activity was above 200 μmol/l/h in 10 patients. A positive correlation was detected for leukocyte β-GBA enzyme levels with cardiac T2* (P=0.024); however, a negative correlation was detected with intraventricular septum thickness (P=0.029) and left heart posterior wall thickness (P=0.030). Conclusion Lower leukocyte β-GBA levels and higher PCT activity may be present in patients with β-TM. There may be an increase in cardiac iron load, intraventricular septum thickness, and left ventricle posterior wall thickness, especially in patients with lower leukocyte β-GBA levels and higher PCT activity. Therefore, leukocyte β-GBA levels and PCT activity may be associated with cardiac complications in patients with β-TM. [ABSTRACT FROM AUTHOR]

Elevated serum chitotriosidase (CHITO) is an indication of macrophage activation, and its capacity have been explored as a marker of inflammation in a number of disease states. For over a decade, CHITO plasma levels have been used by clinicians as a biomarker of inflammation in the lysosomal disease, Gaucher disease, including monitoring response to therapies in patients with Gaucher disease type I. Although it is becoming increasingly recognized that inflammation is a prominent component of many lysosomal diseases, the relation of CHITO levels to disease burden has not been well-characterized in the large majority of lysosomal diseases. Moreover, the role of CHITO in lysosomal diseases that affect the central nervous system (CNS) has not been systematically studied. In this study, one hundred and thirty-four specimens of CSF and serum were collected from 34 patients with lysosomal diseases affecting the CNS. This study included patients with GM1-gangliosidosis, GM2-gangliosidosis, mucopolysaccharidoses (MPS), multiple sulfatase deficiency and Gaucher disease. CHITO levels in the CSF were significantly higher in patients with more rapidly progressing severe neurological impairment: GM1-gangliosidosis vs MPS (p

Cystine-depleting therapy in nephropathic cystinosis is currently monitored via the white blood cell cystine assay, although its application and usefulness are limited by practical and technical issues. Therefore, alternative biomarkers that are widely available, more economical and less technically demanding, while reliably reflecting long-term adherence to cysteamine treatment, are desirable. Recently, we proposed chitotriosidase enzyme activity as a potential novel biomarker for the therapeutic monitoring of cysteamine treatment in cystinosis. In this study, we aimed to validate our previous findings and to confirm the value of chitotriosidase in the management of cystinosis therapy. A retrospective study was conducted on 12 patients treated at the National Institutes of Health Clinical Center and followed up for at least 2 years. Plasma chitotriosidase enzyme activity was correlated with corresponding clinical and biochemical data. Plasma chitotriosidase enzyme activity significantly correlated with WBC cystine levels, cysteamine total daily dosage and a Composite compliance score. Moreover, plasma chitotriosidase was a significant independent predictor for WBC cystine levels, and cut-off values were established in both non-kidney transplanted and kidney transplanted cystinosis patients to distinguish patients with a good versus poor compliance with cysteamine treatment. Our observations are consistent with those of our previous study and validate our findings. Chitotriosidase enzyme activity is a valid potential alternative biomarker for monitoring cysteamine treatment in nephropathic cystinosis patients. Chitotriosidase enzyme activity is a valid potential alternative biomarker for monitoring cysteamine treatment in nephropathic cystinosis patients. [ABSTRACT FROM AUTHOR]

Abstract Background Niemann-Pick disease type C (NP-C) is an inherited neurodegenerative disease (1 per 100 000 newborns) caused by NPC proteins impairment that leads to unesterified cholesterol accumulation in late endosomal/lysosomal compartments. To date the NP-C diagnostics is usually based on cholesterol detection in fibroblasts using an invasive and time-consuming Filipin staining and we need more arguments to widely introduce oxysterols as a biomarkers in NP-C. Methods Insofar as NP-C represents about 8% of all infant cholestases, in this prospective observational study we tried to re-assess the specificity plasma oxysterol and chitotriosidase as a biochemical screening markers of NP-C in children with cholestasis syndrome of unknown origin. For 108 patients (aged from 2 weeks to 7 years) the levels of cholestane-3β,5α,6β-triol (C-triol) and chitotriosidase (ChT) were measured. For patients with elevated C-triol and/or ChT the NPC1 and NPC2 genes were Sanger-sequenced and 47 additional genes (from the custom liver damage panel) were NGS-sequenced. Results Increased C-triol level (> 50 ng/ml) was detected in 4 (of 108) infants with cholestasis syndrome of unknown origin, with following molecular genetic NP-C diagnosis for one patient. Plasma cholesterol significantly correlates with C-triol (p