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Johannes M F G Aerts - One of the best experts on this subject based on the ideXlab platform.
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Value of plasma Chitotriosidase to assess non-neuronopathic Gaucher disease severity and progression in the era of enzyme replacement therapy.
Journal of inherited metabolic disease, 2014Co-Authors: L. Van Dussen, Carla E M Hollak, Rolf G Boot, E. J. Hendriks, Johanna E. M. Groener, Johannes M F G AertsAbstract:Gaucher disease (GD) is caused by deficiency of the enzyme glucocerebrosidase catalysing the regular lysosomal degradation of glucosylceramide. In the common non-neuropathic variant of GD, glucosylceramide-laden macrophages (Gaucher cells) accumulate in various tissues. Gaucher cells secrete Chitotriosidase, an active chitinase, resulting in increased plasma Chitotriosidase levels, which can be sensitively monitored by an enzyme activity assay. Plasma Chitotriosidase is a rough estimate of body burden of Gaucher cells. Non-neuronopathic GD is presently treated by enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). We addressed the question whether plasma Chitotriosidase acts as (predictive) marker of clinical manifestations in non-neuronopathic GD patients receiving treatment. Reductions in plasma Chitotriosidase during therapy correlated with corrections in liver and spleen volumes and showed positive trends with improvements in haemoglobin and platelet count and bone marrow composition. The occurrence of long-term complications and associated conditions such as multiple myeloma, bone complications, Parkinson’s disease, hepatocellular carcinoma and pulmonary hypertension positively correlated with the plasma Chitotriosidase level pre-therapy, the average plasma Chitotriosidase during 3 years of ERT and the residual plasma Chitotriosidase after 2 years of ERT. In summary, plasma Chitotriosidase is a valuable marker in the assessment and follow-up of GD patients.
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curdlan mediated regulation of human phagocyte specific Chitotriosidase
FEBS Letters, 2010Co-Authors: Marco Van Eijk, Tineke Voornbrouwer, Saskia Scheij, Rene G A Boot, Arthur J Verhoeven, Johannes M F G AertsAbstract:Human phagocyte-specific Chitotriosidase is part of innate immunity and shows anti-fungal activity towards chitin-containing fungi. We investigated the effect of stimulation of the C-type lectin receptor dectin-1 by β-1,3-glucan (curdlan) on Chitotriosidase expression and release by human phagocytes. We observed that curdlan triggers Chitotriosidase release from human neutrophils. In addition, we show that curdlan impairs Chitotriosidase induction in monocytes. Finally, curdlan temporarily induces Chitotriosidase in enzyme-expressing monocyte-derived macrophages, followed by reduction of Chitotriosidase expression after prolonged stimulation. These data on regulation of phagocyte-specific Chitotriosidase following curdlan recognition support an important role of Chitotriosidase in the elimination of chitin-containing pathogens.
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Plasma Chitotriosidase and CCL18 as surrogate markers for granulomatous macrophages in sarcoidosis.
Clinica Chimica Acta, 2009Co-Authors: Rolf G Boot, Carla E M Hollak, Marri Verhoek, C Alberts, René E Jonkers, Johannes M F G AertsAbstract:Abstract Background Accumulation of macrophages in multiple organs is a common feature of sarcoidosis and Gaucher disease. The vast number of storage macrophages in Gaucher patients has facilitated the discovery of suitable plasma markers like Chitotriosidase and CCL18. Methods Plasma specimens of patients with sarcoidosis were examined on Chitotriosidase activity and CCL18 protein levels. Results Chitotriosidase was markedly increased, being on average 13.7-fold elevated (range: 1.1–43.3). The sensitivity of demonstrating sarcoidosis using plasma Chitotriosidase values exceeded that using serum angiotensin-converting enzyme values. A 3.5-fold (range: 1–15) increase in CCL18 was also observed. The relative changes in Chitotriosidase and CCL18 during the course of disease closely mimicked each other, suggesting an identical cellular source. In situ hybridization analysis confirmed massive production of Chitotriosidase by sarcoid macrophages. The increase in plasma Chitotriosidase correlated with the stage of disease, being highest in active sarcoidosis with extrapulmonary involvement. Therapy with steroids resulted in clear reduction of plasma Chitotriosidase and CCL18 and relapse of disease activity was preceded by increases in these parameters. Conclusions Sarcoid macrophages secrete high quantities of Chitotriosidase and CCL18. Determination of plasma Chitotriosidase and CCL18 may be useful to monitor changes in granulomatous macrophages during the course of sarcoidosis.
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Different dose-dependent correction of MIP-1β and Chitotriosidase during initial enzyme replacement therapy
Journal of inherited metabolic disease, 2009Co-Authors: M. J. Van Breemen, Carla E M Hollak, Rolf G Boot, M. De Fost, Mario Maas, Maaike G Wiersma, Ludger Wilhelm Poll, S. Vom Dahl, Johannes M F G AertsAbstract:In tissue lesions of type I Gaucher patients, characteristic lipid-laden macrophages, ‘Gaucher cells’, are surrounded by inflammatory phagocytes. Gaucher cells secrete the elevated plasma Chitotriosidase. The elevated plasma MIP-1β in Gaucher patients stems from the phagocytes surrounding the Gaucher cells. Plasma Chitotriosidase and MIP-1β decrease upon successful enzyme replacement therapy (ERT) with mannose-terminated recombinant glucocerebrosidase (alglucerase). Previous histochemical analysis of Gaucher spleens revealed that Gaucher cells express little mannose receptor, in contrast to surrounding phagocytes. We therefore investigated the corrective effects of ERT on plasma MIP-1β and Chitotriosidase in more detail. We also compared effects of one year of treatment with a relatively low dose and a relatively high dose of ERT. A more rapid correction in plasma MIP-1β, compared to Chitotriosidase, was observed in most patients on low-dose ERT. Correction of plasma MIP-1β and Chitotriosidase levels was more pronounced in the higher-dosed patient group. Upon prolonged treatment, differences in the effects of enzyme dose were no longer significant. Normalization of plasma MIP-1β and Chitotriosidase levels was attained in the majority of patients. In conclusion, ERT with mannose-terminated gluocerebrosidase results in prominent corrections of plasma Chitotriosidase, a marker of Gaucher cells, and in particular of plasma MIP-1β, a marker of inflammatory phagocytes. The sharper response in plasma MIP-1β to ERT is in line with the observation that especially phagocytes surrounding Gaucher cells express mannose-receptors.
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Increased Chitotriosidase activity in serum of leprosy patients: association with bacillary leprosy.
Clinical immunology (Orlando Fla.), 2009Co-Authors: Anand M. Iyer, Johannes M F G Aerts, Marco Van Eijk, Eliane Aparecida Silva, Mochammad Hatta, William R. Faber, Pranab DasAbstract:Abstract Human phagocyte-specific Chitotriosidase is associated with several diseases involving macrophage activation. Since macrophage activation plays an important role in the control of Mycobacterium leprae infection, we studied the association of Chitotriosidase with leprosy both in serum and in situ in lesional skin biopsies from patients. Serum samples from 78 Indonesian leprosy patients (39 non-reactional and 39 reactional leprosy patients) and 36 healthy controls (HC) from the same endemic region were investigated. The patients were classified as multibacillary (MB, n = 69) or paucibacillary (PB, n = 9) based on the bacterial index in slit-skin smears. Thirty-six of the reactional patients had erythema nodosum leprosum (ENL), while only 3 had reversal reaction (RR). Follow-up serum samples after corticosteroid treatment were also obtained from 17 patients with ENL and one with RR. Multibacillary (MB) patients showed increased Chitotriosidase activity in serum as compared to paucibacillary (PB) patients and healthy controls. Although no significant difference was observed between reactional and the corresponding non-reactional groups, ENL showed significantly higher Chitotriosidase activity as compared to HC. Furthermore, corticosteroid treatment resulted in significant decline of enzyme activity in ENL sera. Chitotriosidase activity correlated with levels of neopterin, another macrophage activation marker, but not with IL-6, IFN-γ, TNF-α and IL-10. Immunohistochemical staining of 6 MB (LL = 5, BL = 1) lesional skin sections from stored material showed positive staining for Chitotriosidase within lipid-laden macrophages suggesting that macrophages are the source of the enzyme detected in serum. Thus, serum Chitotriosidase activity is potentially useful in distinguishing MB from PB leprosy and in monitoring response to therapy in ENL.
Paola Rottoli - One of the best experts on this subject based on the ideXlab platform.
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Chitotriosidase: A sensitive biomarker of sarcoidosis
European Respiratory Journal, 2011Co-Authors: Elena Bargagli, David A. Bennett, Claudia Maggiorelli, Maria Pieroni, Rosa Metella Refini, Maria Grazia Perari, Paola RottoliAbstract:Chitotriosidase is a member of family of glycosylhydrolases, enzymes involved in the degradation of chitin and chitin-like substrate, identified in a wide variety of organisms. Increased concentrations of Chitotriosidase have been reported in several lysosomal storage diseases and more recently also in sarcoidosis. In this study Chitotriosidase concentrations were evaluated in a population of 233 sarcoidosis patients and 70 controls in order to verify enzyme specificity and sensibility and to evaluate Chitotriosidase prognostic meaning. Chitotriosidase has been found significantly increased in serum of patients with sarcoidosis than in controls (p In conclusion as a new potential biomarker of sarcoidosis severity, Chitotriosidase resulted sensitive, reproducible and easily detectable in serum.
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Serum Chitotriosidase Levels in Patients with Allergic and Non-Allergic Asthma
Respiration; international review of thoracic diseases, 2010Co-Authors: Elena Bargagli, David A. Bennett, Claudia Maggiorelli, Maria Margollicci, Alice Luddi, Carmela Olivieri, M. Perrone, Antje Prasse, Paola RottoliAbstract:Since the data did not have a normal distribution (Shapiro-Wilk’s test), statistical differences were detected by the Kruskal-Wallis test (p !0.05. ) Serum concentrations of Chitotriosidase were 48.72 8 31 nmol/h/ml in allergic asthmatics, 51.5 8 29 nmol/h/ml in non-allergic asmathics and 21.42 8 11 nmol/h/ml in controls ( fig. 1 ). Significant differences were found between the concentrations of Chitotriosidase in asthmatics and controls (p ! 0.05 ). Concentra-tions of Chitotriosidase greater than normal values were observed in 60% of allergic and 63% of non-allergic asthmatics. No signifi-cant differences were found between Chitotriosidase concentra-tions in allergic and non-allergic patients, although the highest concentrations of Chitotriosidase were found in 4 patients with documented allergy to dust and moulds. . a l tj e l ec Tre [8] s tudied serum Chitotriosidase activity in vari-ous lung diseases, finding concentrations of Chitotriosidase in a small population of asthmatics similar to ours. Unfortunately this study did not divide patients according to their history of allergy or specify whether any groups of patients had higher chitotriosi-dase concentrations. Asthma is a complex inflammatory disorder of the airways characterized by bronchial hyper-reactivity to different stimuli, and its pathogenesis is not always completely clear. Chitinases and chitinase-like proteins have recently been proposed as molecules involved in the pathogenesis of asthma with a possible role as prognostic biomarkers [1–6] . Higher serum concentrations of YKL-40 (chitinase-3-like-1), a ‘mammalian chitinase-like protein’, have been reported [2, 4, 5] in asthma patients and hyper-responsive subjects than in con-trols. The YKL-40 gene has been associated with genetic suscep-tibility to the disease. Acid mammalian chitinase (AMCase) has been studied in animal models of airway inflammation [3] and AMCase gene expression has been investigated in detail in BAL fluid macrophages and epithelial brushing from asthma patients [1, 5] . Another member of the chitinase 1 family not yet studied in detail in asthma is Chitotriosidase, an enzyme produced by acti-vated macrophages, structurally similar to YKL-40 but having chitinolytic activity [7, 8] . In the last 5 years our research group has investigated the role of Chitotriosidase in the pathogenesis of different inflammatory lung diseases, such as sarcoidosis [9] . Here we analyzed serum concentrations of Chitotriosidase in al-lergic and non-allergic asthma patients and in a group of controls to evaluate its potential involvement in the different pathways of inflammation occurring in this disease.Ch itotriosidase concentrations were measured in serum sam-ples from 23 patients with allergic asthma, 19 non-allergic asth-matics and 35 healthy controls by a fluorimetric method (Sigma, St. Louis, Mo., USA). Selected patients with PC20 methacholine less than 8 mg/ml were followed at our centre for almost 5 years. They were divided into allergic and non-allergic groups according to medical history, prick test and RAST test results. All patients performed lung function tests, chest X-ray and total IgE analysis at the time of serum sampling. Statistical analysis was performed using Windows software (2005) Graph Pad Prism version 4.0.
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Human Chitotriosidase: A Potential New Marker of Sarcoidosis Severity
Respiration; international review of thoracic diseases, 2008Co-Authors: Elena Bargagli, Claudia Maggiorelli, Paola RottoliAbstract:Sarcoidosis is a multisystemic granulomatous disorder of unknown etiology. The unpredictable clinical course of the disease has prompted research into biomarkers useful for predicting outcome. Among the potential markers of sarcoidosis, a recently proposed indicator was Chitotriosidase, a chitinase produced by activated macrophages. Chitotriosidase is involved in the defense against pathogens containing chitin. Increased concentrations of Chitotriosidase have been observed in a number of lysosomal storage diseases including Gaucher disease and more recently also in sarcoidosis. In 2004, significantly higher serum Chitotriosidase activity was reported for the first time in sarcoidosis patients with respect to controls (p < 0.01); a similar increase was subsequently observed in bronchoalveolar lavage of these patients. In 2007, an increase in enzyme activity was described in juvenile sarcoidosis. Chitotriosidase activity was found to be correlated with angiotensin-converting enzyme levels in serum, radiological stages and quantitative high-resonance CT score for sarcoidosis, suggesting that this enzyme could be a potential marker of disease severity worthy of further study. To evaluate the sensitivity and specificity of this marker, further analysis was done in other granulomatous and diffuse lung diseases. Here, we review the principal literature and the recent evidence of Chitotriosidase as a possible marker of sarcoidosis.
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Chitotriosidase and soluble il 2 receptor comparison of two markers of sarcoidosis severity
Scandinavian Journal of Clinical & Laboratory Investigation, 2008Co-Authors: Elena Bargagli, Nicola Bianchi, Maria Margollicci, Alice Luddi, Salvatore Grosso, Carmela Olivieri, Giuseppe Coviello, Paola RottoliAbstract:Background. Sarcoidosis is a multisystemic granulomatous disease with an unpredictable clinical course characterized by accumulation of activated proliferating T lymphocytes and mononuclear phagocytes in affected organs. Aims and methods. The aims of this study were to describe the clinical, radiological and immunological features of a population of sarcoidosis patients followed at the Sarcoidosis Regional Centre in Siena and to analyse Chitotriosidase and sIL‐2R concentrations in serum of these patients in order to understand their potential as disease markers. Results. Chitotriosidase and sIL‐2R concentrations in serum of sarcoidosis patients were found to be significantly higher than in healthy controls (p<0.01) and a positive correlation between the two markers was documented for the first time. Moreover, Chitotriosidase and sIL‐2R were expressed differently in different radiographic stages of the disease. Conclusion. Chitotriosidase and sIL‐2R are two markers of sarcoidosis of different origin, the v...
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Chitotriosidase activity in patients with interstitial lung diseases
Respiratory medicine, 2007Co-Authors: Elena Bargagli, Maria Grazia Perari, Maria Margollicci, Alice Luddi, Nicolaos Nikiforakis, Salvatore Grosso, Anna Perrone, Paola RottoliAbstract:Summary Background In previous papers, we found significantly higher activity of Chitotriosidase, a macrophage derived enzyme, in serum and BAL of patients with sarcoidosis, especially in those with progressing disease and lung involvement, than in controls. Locally and systemically produced Chitotriosidase activity was correlated with radiological stage and also with degree of lung infiltration, suggesting that this enzyme may play a role in the pathogenesis of sarcoidosis and may be used as a marker of disease severity. Aim To analyse Chitotriosidase activity in serum and bronchoalveolar lavage of patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with systemic sclerosis and to compare it with Chitotriosidase activity in controls and sarcoidosis patients. Methods Chitotriosidase activity was determined by a fluorometric assay. Results The results showed that serum Chitotriosidase activity was only elevated in sarcoidosis patients; in patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with systemic sclerosis it was in the normal range. On the contrary, in BAL of sarcoidosis and idiopathic pulmonary fibrosis patients the activity was significantly higher than in controls. Conclusion Serum Chitotriosidase is a potential marker of sarcoidosis severity; it increases in sarcoidosis in relation to radiological stage and degree of lung infiltration. The increase in Chitotriosidase activity in BAL of sarcoidosis and idiopathic pulmonary fibrosis patients suggests that the enzyme could be involved in fibrogenesis in diffuse lung diseases. Further research is needed to understand the role of Chitotriosidase in the pathogenesis of sarcoidosis and its involvement in fibrotic remodelling in certain diffuse lung diseases.
Salvatore Musumeci - One of the best experts on this subject based on the ideXlab platform.
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Serum YKL-40 levels and Chitotriosidase activity in patients with beta-thalassemia major.
Disease markers, 2014Co-Authors: Maria Letizia Musumeci, Vincenzo Caruso, Emilia Medulla, Venerando Torrisi, Roberta Migale, Silvia Angeletti, Salvatore MusumeciAbstract:Background. YKL-40 association with human disease has been the object of many years of investigation. β-thalassemia patients are affected by hepatic siderosis, which determines a fibrotic process and tissue remodelling. Chitotriosidase has been found to be increased in thalassemic patients returning to normal in patients submitted to bone marrow transplantation. YKL-40 is associated with macrophage activation in liver and in other tissues. The aim of the study was to analyse the level of serum YKL-40 and plasma Chitotriosidase activity of patients with beta-thalassemia to assess whether their expression correlates with liver disease and degree of liver siderosis. Methods. Expression of YKL-40 and Chitotriosidase as a marker of inflammation in 69 thalassemic patients were evaluated. We sought to investigate whether these two chitinases could be considered as a significant biomarker to evaluate therapy effectiveness. Results. Surprisingly we found normal value of YKL-40. We, also, analysed Chitotriosidase activity in the same patients that was slightly increased as a consequence of macrophage activation. Conclusions. These data would suggest a good treatment for these patients.
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Effect of interferon-γ, interleukin-10, lipopolysaccharide and tumor necrosis factor-α on Chitotriosidase synthesis in human macrophages
Clinical chemistry and laboratory medicine, 2005Co-Authors: Michelino Di Rosa, Maria Letizia Musumeci, Anna Scuto, Salvatore Musumeci, Lucia MalaguarneraAbstract:Human Chitotriosidase is a chitinolytic enzyme and mainly produced by activated macrophages. Recently, we observed that prolactin, which is structurally related to several cytokines and is involved in regulating monocyte/macrophage functions, upregulates Chitotriosidase gene expression in human macrophages, suggesting that Chitotriosidase is not only a biochemical marker of macrophage activation in lysosomal diseases and hematological disorders, but also may reflect induction of an immunological response. To confirm this hypothesis we evaluated by quantitative real-time PCR the mRNA Chitotriosidase levels in human monocytes/macrophages following treatment with pro-inflammatory stimuli such as interferon-γ, tumor necrosis factor-a, lipopolysaccharide, and interleukin-10, an anti-inflammatory cytokine. Stimulation of macrophages with interferon-γ, tumor necrosis factor-a and lipopolysaccharide resulted in increased levels of Chitotriosidase mRNA, as well as Chitotriosidase activity, whereas interleukin-10 decreased Chitotriosidase synthesis. This finding is consistent with the hypothesis that the production of Chitotriosidase by macrophages could have biological relevance in the immune response.
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plasma Chitotriosidase activity in acute plasmodium falciparum malaria
Clinica Chimica Acta, 2003Co-Authors: R Barone, Lucia Malaguarnera, J Simporè, Salvatore Pignatelli, Salvatore MusumeciAbstract:Background: Chitotriosidase is a functional chitinase secreted by activated macrophages. It is encoded by a gene located on chromosome 1q31-32, whose mutations may be responsible for Chitotriosidase deficiency, encountered in almost 6% of Caucasian population. Objective: This study reports firstly plasma Chitotriosidase activity in African children with acute Plasmodium falciparum malaria. The Chitotriosidase activity was correlated to objective parameters reflecting the status of the disease and compared with those found in healthy African children. Results: We found that plasma Chitotriosidase levels are significantly increased in African children with acute malaria (185.0±141.0 nmol/h/ml; median 150; range 11–521) with respect to reference values obtained in age matched African children (84.4.5±72.8 nmol/ml/h; median 63; range 4–350) (P<0.001). Moreover the levels of Chitotriosidase were higher in African children than in Caucasian children matched for age (28.86±18.7 nmol/h/ml; median 24; range 1–98) (P<0.0001). A remarkable significant correlation was found between plasma Chitotriosidase and reticulo-endothelial activation, as judged by thrombocytopenia degree and serum ferritin level in children with acute malaria. Conclusion: Based on this study, it appears that genetic and environmental features might be responsible for diversity of plasma Chitotriosidase activity in black children living in Burkina Faso.
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plasma Chitotriosidase activity in acute plasmodium falciparum malaria
Journal of Tropical Pediatrics, 2003Co-Authors: R Barone, Lucia Malaguarnera, J Simporè, Salvatore Pignatelli, Salvatore MusumeciAbstract:Background: Chitotriosidase is a functional chitinase secreted by activated macrophages. It is encoded by a gene located on chromosome 1q31-32, whose mutations may be responsible for Chitotriosidase deficiency, encountered in almost 6% of Caucasian population. Objective: This study reports firstly plasma Chitotriosidase activity in African children with acute Plasmodium falciparum malaria. The Chitotriosidase activity was correlated to objective parameters reflecting the status of the disease and compared with those found in healthy African children. Results: We found that plasma Chitotriosidase levels are significantly increased in African children with acute malaria (185.0F141.0 nmol/h/ml; median 150; range 11–521) with respect to reference values obtained in age matched African children (84.4.5F72.8 nmol/ml/h; median 63; range 4–350) (P<0.001). Moreover the levels of Chitotriosidase were higher in African children than in Caucasian children matched for age (28.86F18.7 nmol/h/ml; median 24; range 1–98) (P<0.0001). A remarkable significant correlation was found between plasma Chitotriosidase and reticulo-endothelial activation, as judged by thrombocytopenia degree and serum ferritin level in children with acute malaria. Conclusion: Based on this study, it appears that genetic and environmental features might be responsible for diversity of plasma Chitotriosidase activity in black children living in Burkina Faso. D 2003 Elsevier Science B.V. All rights reserved.
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Plasma Chitotriosidase activity in acute Plasmodium falciparum malaria.
Journal of tropical pediatrics, 2003Co-Authors: R Barone, Lucia Malaguarnera, J Simporè, Salvatore Pignatelli, Salvatore MusumeciAbstract:Background: Chitotriosidase is a functional chitinase secreted by activated macrophages. It is encoded by a gene located on chromosome 1q31-32, whose mutations may be responsible for Chitotriosidase deficiency, encountered in almost 6% of Caucasian population. Objective: This study reports firstly plasma Chitotriosidase activity in African children with acute Plasmodium falciparum malaria. The Chitotriosidase activity was correlated to objective parameters reflecting the status of the disease and compared with those found in healthy African children. Results: We found that plasma Chitotriosidase levels are significantly increased in African children with acute malaria (185.0F141.0 nmol/h/ml; median 150; range 11–521) with respect to reference values obtained in age matched African children (84.4.5F72.8 nmol/ml/h; median 63; range 4–350) (P
Rolf G Boot - One of the best experts on this subject based on the ideXlab platform.
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Value of plasma Chitotriosidase to assess non-neuronopathic Gaucher disease severity and progression in the era of enzyme replacement therapy.
Journal of inherited metabolic disease, 2014Co-Authors: L. Van Dussen, Carla E M Hollak, Rolf G Boot, E. J. Hendriks, Johanna E. M. Groener, Johannes M F G AertsAbstract:Gaucher disease (GD) is caused by deficiency of the enzyme glucocerebrosidase catalysing the regular lysosomal degradation of glucosylceramide. In the common non-neuropathic variant of GD, glucosylceramide-laden macrophages (Gaucher cells) accumulate in various tissues. Gaucher cells secrete Chitotriosidase, an active chitinase, resulting in increased plasma Chitotriosidase levels, which can be sensitively monitored by an enzyme activity assay. Plasma Chitotriosidase is a rough estimate of body burden of Gaucher cells. Non-neuronopathic GD is presently treated by enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). We addressed the question whether plasma Chitotriosidase acts as (predictive) marker of clinical manifestations in non-neuronopathic GD patients receiving treatment. Reductions in plasma Chitotriosidase during therapy correlated with corrections in liver and spleen volumes and showed positive trends with improvements in haemoglobin and platelet count and bone marrow composition. The occurrence of long-term complications and associated conditions such as multiple myeloma, bone complications, Parkinson’s disease, hepatocellular carcinoma and pulmonary hypertension positively correlated with the plasma Chitotriosidase level pre-therapy, the average plasma Chitotriosidase during 3 years of ERT and the residual plasma Chitotriosidase after 2 years of ERT. In summary, plasma Chitotriosidase is a valuable marker in the assessment and follow-up of GD patients.
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Plasma Chitotriosidase and CCL18 as surrogate markers for granulomatous macrophages in sarcoidosis.
Clinica chimica acta; international journal of clinical chemistry, 2009Co-Authors: Rolf G Boot, Carla E M Hollak, Marri Verhoek, C Alberts, René E Jonkers, Johannes M AertsAbstract:Accumulation of macrophages in multiple organs is a common feature of sarcoidosis and Gaucher disease. The vast number of storage macrophages in Gaucher patients has facilitated the discovery of suitable plasma markers like Chitotriosidase and CCL18. Plasma specimens of patients with sarcoidosis were examined on Chitotriosidase activity and CCL18 protein levels. Chitotriosidase was markedly increased, being on average 13.7-fold elevated (range: 1.1-43.3). The sensitivity of demonstrating sarcoidosis using plasma Chitotriosidase values exceeded that using serum angiotensin-converting enzyme values. A 3.5-fold (range: 1-15) increase in CCL18 was also observed. The relative changes in Chitotriosidase and CCL18 during the course of disease closely mimicked each other, suggesting an identical cellular source. In situ hybridization analysis confirmed massive production of Chitotriosidase by sarcoid macrophages. The increase in plasma Chitotriosidase correlated with the stage of disease, being highest in active sarcoidosis with extrapulmonary involvement. Therapy with steroids resulted in clear reduction of plasma Chitotriosidase and CCL18 and relapse of disease activity was preceded by increases in these parameters. Sarcoid macrophages secrete high quantities of Chitotriosidase and CCL18. Determination of plasma Chitotriosidase and CCL18 may be useful to monitor changes in granulomatous macrophages during the course of sarcoidosis.
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Plasma Chitotriosidase and CCL18 as surrogate markers for granulomatous macrophages in sarcoidosis.
Clinica Chimica Acta, 2009Co-Authors: Rolf G Boot, Carla E M Hollak, Marri Verhoek, C Alberts, René E Jonkers, Johannes M F G AertsAbstract:Abstract Background Accumulation of macrophages in multiple organs is a common feature of sarcoidosis and Gaucher disease. The vast number of storage macrophages in Gaucher patients has facilitated the discovery of suitable plasma markers like Chitotriosidase and CCL18. Methods Plasma specimens of patients with sarcoidosis were examined on Chitotriosidase activity and CCL18 protein levels. Results Chitotriosidase was markedly increased, being on average 13.7-fold elevated (range: 1.1–43.3). The sensitivity of demonstrating sarcoidosis using plasma Chitotriosidase values exceeded that using serum angiotensin-converting enzyme values. A 3.5-fold (range: 1–15) increase in CCL18 was also observed. The relative changes in Chitotriosidase and CCL18 during the course of disease closely mimicked each other, suggesting an identical cellular source. In situ hybridization analysis confirmed massive production of Chitotriosidase by sarcoid macrophages. The increase in plasma Chitotriosidase correlated with the stage of disease, being highest in active sarcoidosis with extrapulmonary involvement. Therapy with steroids resulted in clear reduction of plasma Chitotriosidase and CCL18 and relapse of disease activity was preceded by increases in these parameters. Conclusions Sarcoid macrophages secrete high quantities of Chitotriosidase and CCL18. Determination of plasma Chitotriosidase and CCL18 may be useful to monitor changes in granulomatous macrophages during the course of sarcoidosis.
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Different dose-dependent correction of MIP-1β and Chitotriosidase during initial enzyme replacement therapy
Journal of inherited metabolic disease, 2009Co-Authors: M. J. Van Breemen, Carla E M Hollak, Rolf G Boot, M. De Fost, Mario Maas, Maaike G Wiersma, Ludger Wilhelm Poll, S. Vom Dahl, Johannes M F G AertsAbstract:In tissue lesions of type I Gaucher patients, characteristic lipid-laden macrophages, ‘Gaucher cells’, are surrounded by inflammatory phagocytes. Gaucher cells secrete the elevated plasma Chitotriosidase. The elevated plasma MIP-1β in Gaucher patients stems from the phagocytes surrounding the Gaucher cells. Plasma Chitotriosidase and MIP-1β decrease upon successful enzyme replacement therapy (ERT) with mannose-terminated recombinant glucocerebrosidase (alglucerase). Previous histochemical analysis of Gaucher spleens revealed that Gaucher cells express little mannose receptor, in contrast to surrounding phagocytes. We therefore investigated the corrective effects of ERT on plasma MIP-1β and Chitotriosidase in more detail. We also compared effects of one year of treatment with a relatively low dose and a relatively high dose of ERT. A more rapid correction in plasma MIP-1β, compared to Chitotriosidase, was observed in most patients on low-dose ERT. Correction of plasma MIP-1β and Chitotriosidase levels was more pronounced in the higher-dosed patient group. Upon prolonged treatment, differences in the effects of enzyme dose were no longer significant. Normalization of plasma MIP-1β and Chitotriosidase levels was attained in the majority of patients. In conclusion, ERT with mannose-terminated gluocerebrosidase results in prominent corrections of plasma Chitotriosidase, a marker of Gaucher cells, and in particular of plasma MIP-1β, a marker of inflammatory phagocytes. The sharper response in plasma MIP-1β to ERT is in line with the observation that especially phagocytes surrounding Gaucher cells express mannose-receptors.
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TLR- and NOD2-dependent regulation of human phagocyte-specific Chitotriosidase.
FEBS letters, 2007Co-Authors: Marco Van Eijk, Saskia Scheij, Rolf G Boot, Cindy P. A. A. Van Roomen, Dave Speijer, Johannes M F G AertsAbstract:Human Chitotriosidase is specifically expressed by phagocytes, has anti-fungal activity towards chitin-containing fungi in vitro and in vivo, and is part of innate immunity. We studied the effect of toll-like receptor (TLR)- and nucleotide-binding oligomerization domain (NOD)-2 triggering on Chitotriosidase expression and release by phagocytes. We find that TLR, but not NOD2 activation, regulates Chitotriosidase release by neutrophils. Furthermore, both TLR and NOD2 activation resulted in diminished induction by monocytes. Lastly, NOD2 activation, but not TLR stimulation, induces chitinase expression in macrophages. We conclude that phagocyte-specific regulation is important for efficient eradication of chitin-containing pathogens.
Elena Bargagli - One of the best experts on this subject based on the ideXlab platform.
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Chitotriosidase: A sensitive biomarker of sarcoidosis
European Respiratory Journal, 2011Co-Authors: Elena Bargagli, David A. Bennett, Claudia Maggiorelli, Maria Pieroni, Rosa Metella Refini, Maria Grazia Perari, Paola RottoliAbstract:Chitotriosidase is a member of family of glycosylhydrolases, enzymes involved in the degradation of chitin and chitin-like substrate, identified in a wide variety of organisms. Increased concentrations of Chitotriosidase have been reported in several lysosomal storage diseases and more recently also in sarcoidosis. In this study Chitotriosidase concentrations were evaluated in a population of 233 sarcoidosis patients and 70 controls in order to verify enzyme specificity and sensibility and to evaluate Chitotriosidase prognostic meaning. Chitotriosidase has been found significantly increased in serum of patients with sarcoidosis than in controls (p In conclusion as a new potential biomarker of sarcoidosis severity, Chitotriosidase resulted sensitive, reproducible and easily detectable in serum.
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Serum Chitotriosidase Levels in Patients with Allergic and Non-Allergic Asthma
Respiration; international review of thoracic diseases, 2010Co-Authors: Elena Bargagli, David A. Bennett, Claudia Maggiorelli, Maria Margollicci, Alice Luddi, Carmela Olivieri, M. Perrone, Antje Prasse, Paola RottoliAbstract:Since the data did not have a normal distribution (Shapiro-Wilk’s test), statistical differences were detected by the Kruskal-Wallis test (p !0.05. ) Serum concentrations of Chitotriosidase were 48.72 8 31 nmol/h/ml in allergic asthmatics, 51.5 8 29 nmol/h/ml in non-allergic asmathics and 21.42 8 11 nmol/h/ml in controls ( fig. 1 ). Significant differences were found between the concentrations of Chitotriosidase in asthmatics and controls (p ! 0.05 ). Concentra-tions of Chitotriosidase greater than normal values were observed in 60% of allergic and 63% of non-allergic asthmatics. No signifi-cant differences were found between Chitotriosidase concentra-tions in allergic and non-allergic patients, although the highest concentrations of Chitotriosidase were found in 4 patients with documented allergy to dust and moulds. . a l tj e l ec Tre [8] s tudied serum Chitotriosidase activity in vari-ous lung diseases, finding concentrations of Chitotriosidase in a small population of asthmatics similar to ours. Unfortunately this study did not divide patients according to their history of allergy or specify whether any groups of patients had higher chitotriosi-dase concentrations. Asthma is a complex inflammatory disorder of the airways characterized by bronchial hyper-reactivity to different stimuli, and its pathogenesis is not always completely clear. Chitinases and chitinase-like proteins have recently been proposed as molecules involved in the pathogenesis of asthma with a possible role as prognostic biomarkers [1–6] . Higher serum concentrations of YKL-40 (chitinase-3-like-1), a ‘mammalian chitinase-like protein’, have been reported [2, 4, 5] in asthma patients and hyper-responsive subjects than in con-trols. The YKL-40 gene has been associated with genetic suscep-tibility to the disease. Acid mammalian chitinase (AMCase) has been studied in animal models of airway inflammation [3] and AMCase gene expression has been investigated in detail in BAL fluid macrophages and epithelial brushing from asthma patients [1, 5] . Another member of the chitinase 1 family not yet studied in detail in asthma is Chitotriosidase, an enzyme produced by acti-vated macrophages, structurally similar to YKL-40 but having chitinolytic activity [7, 8] . In the last 5 years our research group has investigated the role of Chitotriosidase in the pathogenesis of different inflammatory lung diseases, such as sarcoidosis [9] . Here we analyzed serum concentrations of Chitotriosidase in al-lergic and non-allergic asthma patients and in a group of controls to evaluate its potential involvement in the different pathways of inflammation occurring in this disease.Ch itotriosidase concentrations were measured in serum sam-ples from 23 patients with allergic asthma, 19 non-allergic asth-matics and 35 healthy controls by a fluorimetric method (Sigma, St. Louis, Mo., USA). Selected patients with PC20 methacholine less than 8 mg/ml were followed at our centre for almost 5 years. They were divided into allergic and non-allergic groups according to medical history, prick test and RAST test results. All patients performed lung function tests, chest X-ray and total IgE analysis at the time of serum sampling. Statistical analysis was performed using Windows software (2005) Graph Pad Prism version 4.0.
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Human Chitotriosidase: A Potential New Marker of Sarcoidosis Severity
Respiration; international review of thoracic diseases, 2008Co-Authors: Elena Bargagli, Claudia Maggiorelli, Paola RottoliAbstract:Sarcoidosis is a multisystemic granulomatous disorder of unknown etiology. The unpredictable clinical course of the disease has prompted research into biomarkers useful for predicting outcome. Among the potential markers of sarcoidosis, a recently proposed indicator was Chitotriosidase, a chitinase produced by activated macrophages. Chitotriosidase is involved in the defense against pathogens containing chitin. Increased concentrations of Chitotriosidase have been observed in a number of lysosomal storage diseases including Gaucher disease and more recently also in sarcoidosis. In 2004, significantly higher serum Chitotriosidase activity was reported for the first time in sarcoidosis patients with respect to controls (p < 0.01); a similar increase was subsequently observed in bronchoalveolar lavage of these patients. In 2007, an increase in enzyme activity was described in juvenile sarcoidosis. Chitotriosidase activity was found to be correlated with angiotensin-converting enzyme levels in serum, radiological stages and quantitative high-resonance CT score for sarcoidosis, suggesting that this enzyme could be a potential marker of disease severity worthy of further study. To evaluate the sensitivity and specificity of this marker, further analysis was done in other granulomatous and diffuse lung diseases. Here, we review the principal literature and the recent evidence of Chitotriosidase as a possible marker of sarcoidosis.
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Chitotriosidase and soluble il 2 receptor comparison of two markers of sarcoidosis severity
Scandinavian Journal of Clinical & Laboratory Investigation, 2008Co-Authors: Elena Bargagli, Nicola Bianchi, Maria Margollicci, Alice Luddi, Salvatore Grosso, Carmela Olivieri, Giuseppe Coviello, Paola RottoliAbstract:Background. Sarcoidosis is a multisystemic granulomatous disease with an unpredictable clinical course characterized by accumulation of activated proliferating T lymphocytes and mononuclear phagocytes in affected organs. Aims and methods. The aims of this study were to describe the clinical, radiological and immunological features of a population of sarcoidosis patients followed at the Sarcoidosis Regional Centre in Siena and to analyse Chitotriosidase and sIL‐2R concentrations in serum of these patients in order to understand their potential as disease markers. Results. Chitotriosidase and sIL‐2R concentrations in serum of sarcoidosis patients were found to be significantly higher than in healthy controls (p<0.01) and a positive correlation between the two markers was documented for the first time. Moreover, Chitotriosidase and sIL‐2R were expressed differently in different radiographic stages of the disease. Conclusion. Chitotriosidase and sIL‐2R are two markers of sarcoidosis of different origin, the v...
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Chitotriosidase activity in patients with interstitial lung diseases
Respiratory medicine, 2007Co-Authors: Elena Bargagli, Maria Grazia Perari, Maria Margollicci, Alice Luddi, Nicolaos Nikiforakis, Salvatore Grosso, Anna Perrone, Paola RottoliAbstract:Summary Background In previous papers, we found significantly higher activity of Chitotriosidase, a macrophage derived enzyme, in serum and BAL of patients with sarcoidosis, especially in those with progressing disease and lung involvement, than in controls. Locally and systemically produced Chitotriosidase activity was correlated with radiological stage and also with degree of lung infiltration, suggesting that this enzyme may play a role in the pathogenesis of sarcoidosis and may be used as a marker of disease severity. Aim To analyse Chitotriosidase activity in serum and bronchoalveolar lavage of patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with systemic sclerosis and to compare it with Chitotriosidase activity in controls and sarcoidosis patients. Methods Chitotriosidase activity was determined by a fluorometric assay. Results The results showed that serum Chitotriosidase activity was only elevated in sarcoidosis patients; in patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with systemic sclerosis it was in the normal range. On the contrary, in BAL of sarcoidosis and idiopathic pulmonary fibrosis patients the activity was significantly higher than in controls. Conclusion Serum Chitotriosidase is a potential marker of sarcoidosis severity; it increases in sarcoidosis in relation to radiological stage and degree of lung infiltration. The increase in Chitotriosidase activity in BAL of sarcoidosis and idiopathic pulmonary fibrosis patients suggests that the enzyme could be involved in fibrogenesis in diffuse lung diseases. Further research is needed to understand the role of Chitotriosidase in the pathogenesis of sarcoidosis and its involvement in fibrotic remodelling in certain diffuse lung diseases.