A 20-Year Longitudinal Study of Plasma Chitotriosidase Activity in Treated Gaucher Disease Type 1 and 3 Patients—A Qualitative and Quantitative Approach
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,...
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MDPI AG
2023-02-01
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| Online Access: | https://www.mdpi.com/2218-273X/13/3/436 |
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| author | Paulina Szymańska-Rożek Barbara Czartoryska Grazina Kleinotiene Patryk Lipiński Anna Tylki-Szymańska Agnieszka Ługowska |
| author_facet | Paulina Szymańska-Rożek Barbara Czartoryska Grazina Kleinotiene Patryk Lipiński Anna Tylki-Szymańska Agnieszka Ługowska |
| author_sort | Paulina Szymańska-Rożek |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T06:52:37Z |
| format | Article |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T06:52:37Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-79e52e996b27402fb90ce9e55d4222332023-11-17T09:51:16ZengMDPI AGBiomolecules2218-273X2023-02-0113343610.3390/biom13030436A 20-Year Longitudinal Study of Plasma Chitotriosidase Activity in Treated Gaucher Disease Type 1 and 3 Patients—A Qualitative and Quantitative ApproachPaulina Szymańska-Rożek0Barbara Czartoryska1Grazina Kleinotiene2Patryk Lipiński3Anna Tylki-Szymańska4Agnieszka Ługowska5Faculty of Mathematics, Informatics, and Mechanics, University of Warsaw, 02-097 Warsaw, PolandDepartment of Genetics, Institute of Psychiatry and Neurology, 02-957 Warsaw, PolandFaculty of Medicine, Vilnius University, 03101 Vilnius, LithuaniaDepartment of Pediatrics, Nutrition and Metabolic Diseases, The Children’s Memorial Health Institute, 04-730 Warsaw, PolandDepartment of Pediatrics, Nutrition and Metabolic Diseases, The Children’s Memorial Health Institute, 04-730 Warsaw, PolandDepartment of Genetics, Institute of Psychiatry and Neurology, 02-957 Warsaw, PolandChitotriosidase 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.https://www.mdpi.com/2218-273X/13/3/436chitotriosidaseGaucher diseasemacrophagesenzyme replacement therapy |
| spellingShingle | Paulina Szymańska-Rożek Barbara Czartoryska Grazina Kleinotiene Patryk Lipiński Anna Tylki-Szymańska Agnieszka Ługowska A 20-Year Longitudinal Study of Plasma Chitotriosidase Activity in Treated Gaucher Disease Type 1 and 3 Patients—A Qualitative and Quantitative Approach Biomolecules chitotriosidase Gaucher disease macrophages enzyme replacement therapy |
| title | A 20-Year Longitudinal Study of Plasma Chitotriosidase Activity in Treated Gaucher Disease Type 1 and 3 Patients—A Qualitative and Quantitative Approach |
| title_full | A 20-Year Longitudinal Study of Plasma Chitotriosidase Activity in Treated Gaucher Disease Type 1 and 3 Patients—A Qualitative and Quantitative Approach |
| title_fullStr | A 20-Year Longitudinal Study of Plasma Chitotriosidase Activity in Treated Gaucher Disease Type 1 and 3 Patients—A Qualitative and Quantitative Approach |
| title_full_unstemmed | A 20-Year Longitudinal Study of Plasma Chitotriosidase Activity in Treated Gaucher Disease Type 1 and 3 Patients—A Qualitative and Quantitative Approach |
| title_short | A 20-Year Longitudinal Study of Plasma Chitotriosidase Activity in Treated Gaucher Disease Type 1 and 3 Patients—A Qualitative and Quantitative Approach |
| title_sort | 20 year longitudinal study of plasma chitotriosidase activity in treated gaucher disease type 1 and 3 patients a qualitative and quantitative approach |
| topic | chitotriosidase Gaucher disease macrophages enzyme replacement therapy |
| url | https://www.mdpi.com/2218-273X/13/3/436 |
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