ArticleOrphanet journal of rare diseases2014
Clinical utility of chitotriosidase enzyme activity in nephropathic cystinosis.
Article in Orphanet journal of rare diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- From Molecular Understanding and Pathophysiology to Disease Management; A Practical Approach and Guidance to the Management of the Ocular Manifestations of Cystinosis.International journal of molecular sciences · 2025Review
- Role of Biomarkers in Diagnosing Disease, Assessing the Severity and Progression of Disease, and Evaluating the Efficacy of Therapies.Journal of inherited metabolic disease · 2025Review
- Long-Term Treatment of Gaucher Disease with Velaglucerase Alfa in ERT-Naïve Patients from the Gaucher Outcome Survey (GOS) Registry.Journal of clinical medicine · 2024Article
- Metabolomic Analyses to Identify Candidate Biomarkers of Cystinosis.International journal of molecular sciences · 2023Article
- Clinical and neurophysiological characterization of early neuromuscular involvement in children and adolescents with nephropathic cystinosis.Pediatric nephrology (Berlin, Germany) · 2022Article
- Review
- Nephropathic Cystinosis: Pathogenic Roles of Inflammation and Potential for New Therapies.Cells · 2022Review
- Article
- Inherited disorders of lysosomal membrane transporters.Biochimica et biophysica acta. Biomembranes · 2020Review
- Chitotriosidase as a Novel Biomarker for Therapeutic Monitoring of Nephropathic Cystinosis.Journal of the American Society of Nephrology : JASN · 2020Article
- Cystinosis (ctns) zebrafish mutant shows pronephric glomerular and tubular dysfunction.Scientific reports · 2017Article
- Cystinosis: a review.Orphanet journal of rare diseases · 2016Review
- Serum chitotriosidase in postmenopausal women with severe osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2016Article
- Immunomodulatory Effects of Chitotriosidase Enzyme.Enzyme research · 2016Review
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNephropathic cystinosis is an inherited autosomal recessive lysosomal storage disorder characterized by the pathological accumulation and crystallization of cystine inside different cell types. WBC cystine determination forms the basis for the diagnosis and therapeutic monitoring with the cystine depleting drug (cysteamine). The chitotriosidase enzyme is a human chitinase, produced by activated macrophages. Its elevation is documented in several lysosomal storage disorders. Although, about 6% of Caucasians have enzyme deficiency due to homozygosity of 24-bp duplication mutation in the chitotriosidase gene, it is currently established as a screening marker and therapeutic monitor for Gaucher's disease.
methodsPlasma chitotriosidase activity was measured in 45 cystinotic patients, and compared with 87 healthy controls and 54 renal disease patients with different degrees of renal failure (CKD1-5). Chitotriosidase levels were also correlated with WBC cystine in 32 treated patients. Furthermore, we incubated control human macrophages in-vitro with different concentrations of cystine crystals and monitored the response of tumor necrosis factor-alpha (TNF-α) and chitotriosidase activity. We also compared plasma chitotriosidase activity in cystinotic knocked-out (n = 10) versus wild-type mice (n = 10).
resultsPlasma chitotriosidase activity in cystinotic patients (0-3880, median 163 nmol/ml/h) was significantly elevated compared to healthy controls (0-90, median 18 nmol/ml/h) and to CKD patients (0-321, median 52 nmol/ml/h), P < 0.001 for both groups. Controls with decreased renal function had mild to moderate chitotriosidase elevations; however, their levels were significantly lower than in cystinotic patients with comparable degree of renal insufficiency. Chitotriosidase activity positively correlated with WBC cystine content for patients on cysteamine therapy (r = 0.8), P < 0.001. In culture, human control macrophages engulfed cystine crystals and released TNF-α into culture supernatant in a crystal concentration dependent manner. Chitotriosidase activity was also significantly increased in macrophage supernatant and cell-lysate. Furthermore, chitotriosidase activity was significantly higher in cystinotic knocked-out than in the wild-type mice, P = 0.003.
conclusionsThis study indicates that cystine crystals are potent activators of human macrophages and that chitotriosidase activity is a useful marker for this activation and a promising clinical biomarker and therapeutic monitor for nephropathic cystinosis.
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