Serum levels of chitotriosidase as a marker of disease activity and clinical stage in sarcoidosis

Grosso, Salvatore; Margollicci, Maria; Bargagli, Elena; Buccoliero, Qr; Perrone, Anna; Galimberti, Daniela; Morgese, G; Balestri, Paolo; Rottoli, Paola

doi:10.1080/00365510410004092

Cited by 61 publications

(51 citation statements)

References 28 publications

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“…Chitotriosidase is the dominant chitinase in man that is highly expressed in specific cell types including tissue macrophages. In various disorders in which activated macrophages are implicated, elevated plasma chitotriosidase levels occur, e.g., lysosomal lipid storage disorders, sarcoidosis, visceral Leishmaniasis, extended atherosclerosis such as Tangier disease, and thalassemia (Hollak et al 1994;Barone et al 1999;Boot et al 1999;Grosso et al 2004). In sharp contrast, in mice, expression of chitotriosidase is confined to the gastrointestinal tract and AMCase seems to be the sole endogenous chitinase in tissues such as lung.…”

Section: Discussionmentioning

confidence: 99%

Marked Differences in Tissue-specific Expression of Chitinases in Mouse and Man

Boot

Bussink

Verhoek

et al. 2005

J Histochem Cytochem.

124

138

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S U M M A R Y Two distinct chitinases have been identified in mammals: a phagocyte-specific enzyme named chitotriosidase and an acidic mammalian chitinase (AMCase) expressed in the lungs and gastrointestinal tract. Increased expression of both chitinases has been observed in different pathological conditions: chitotriosidase in lysosomal lipid storage disorders like Gaucher disease and AMCase in asthmatic lung disease. Recently, it was reported that AMCase activity is involved in the pathogenesis of asthma in an induced mouse model. Inhibition of chitinase activity was found to alleviate the inflammation-driven pathology. We studied the tissue-specific expression of both chitinases in mice and compared it to the situation in man. In both species AMCase is expressed in alveolar macrophages and in the gastrointestinal tract. In mice, chitotriosidase is expressed only in the gastrointestinal tract, the tongue, fore-stomach, and Paneth cells in the small intestine, whereas in man the enzyme is expressed exclusively by professional phagocytes. This species difference seems to be mediated by distinct promoter usage. In conclusion, the pattern of expression of chitinases in the lung differs between mouse and man. The implications for the development of anti-asthma drugs with chitinases as targets are discussed.

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Section: Discussionmentioning

confidence: 99%

Marked Differences in Tissue-specific Expression of Chitinases in Mouse and Man

Boot

Bussink

Verhoek

et al. 2005

J Histochem Cytochem.

124

138

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“…acute Plasmodium falciparum malaria and visceral leishmaniasis [5,6,7,8,9,10]. Increased activity has also been found in the cerebrospinal fluid but not in the serum of patients with multiple sclerosis [5], urine of neonates with bacterial and fungal infections [11] and in the serum and bronchoalveolar lavage (BAL) of sarcoidosis patients [12, 13]. …”

Section: Introductionmentioning

confidence: 99%

“…Activated macrophages are also involved in the pathogenesis of the disease via the release of mediators, e.g. cytokines, chemokines and enzymes [12,16,17,18,19,20]. …”

Section: Introductionmentioning

confidence: 99%

Chitotriosidase Activity in the Serum of Patients with Sarcoidosis and Pulmonary Tuberculosis

Bargagli

Margollicci²,

Nikiforakis³

et al. 2007

Respiration

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Background: Human chitotriosidase is a chitinase selectively expressed by activated macrophages. An increase in chitotriosidase activity was previously described by us in the serum and bronchoalveolar lavage of sarcoidosis patients. Objective: The aim of the present study was to analyze serum chitotriosidase activity in a larger number of sarcoidosis patients to verify the reported increase with respect to controls and to compare serum chitotriosidase levels in patients with sarcoidosis and tuberculosis, two granulomatous disorders of different etiology. Methods: Chitotriosidase activity was measured in the serum of 96 sarcoidosis patients, 15 pulmonary tuberculosis patients and 30 healthy controls. Results: We found significantly higher serum chitotriosidase activity in sarcoidosis patients than controls (p < 0.01) and in sarcoidosis patients than tuberculosis patients (p < 0.01), confirming a striking elevation of chitotriosidase activity (>10 times greater than normal) in pulmonary sarcoidosis patients. This is the first time that chitotriosidase activity has been analyzed in the serum of patients with pulmonary tuberculosis; it was found to be significantly lower than in sarcoidosis patients and not significantly greater than in controls. Conclusion: Although the mechanisms leading to the increase in chitotriosidase activity in sarcoidosis are still unknown, this enzyme may be specifically involved in the pathogenesis of the disease. Further studies with a greater number of patients are needed to confirm these results and to determine whether chitotriosidase could be a marker with diagnostic or prognostic value in sarcoidosis.

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“…Additional evidence of a role for chitotriosidase during immunological responses is the observation that the enzyme is shortly and acutely up-regulated, both at the level of RNA and in activity following stimulation with prolactin, IFN-c, TNFa, LPS, and IL-4 (Di Rosa et al 2005;Malaguarnera et al 2004;van Eijk et al 2005). Moreover, CHIT activity has been used in the screening of lysosomal storage diseases (Grosso et al 2004) and in the monitoring of the treatment of Gaucher disease (CabreraSalazar et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Human CHIT1 gene distribution: new data from Mediterranean and European populations

et al. 2006

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A 24 bp duplication in the CHIT1 gene (H allele) is associated with a deficiency in the activity of chitotriosidase, an enzyme with the capability to hydrolyse chitin. A recent study in European and two sub-Saharan populations suggested a relationship between the presence of the mutation, improved environmental conditions, and the disappearance of parasitic diseases, including Plasmodium falciparum malaria. This result was not supported by the high frequency of the 24 bp duplication in a sample from Taiwan, an area with high malaria endemicity until 40 years ago. In this study, we analysed the frequency variability of the H allele in Mediterranean populations and its internal variability in Sardinia (Italy) with respect to malaria, which had been endemic on the island until its eradication during [1946][1947][1948][1949][1950]. The pattern of H frequency distributions is not consistent with the hypothesis of selective pressures acting on CHIT1 gene. The Moran's index coefficient and correlogram seem to indicate, indeed, that allele distribution was determined by random factors. The pattern of frequency distribution suggests a possible Asiatic origin of the H allele, but it could be possible also that the mutant allele had diffused out of Africa, and was subsequently lost from African populations.

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Serum levels of chitotriosidase as a marker of disease activity and clinical stage in sarcoidosis

Abstract: Although the data need to be validated by further investigation, the observations made in this study seem to indicate that serum chitotriosidase concentrations may be a useful marker for monitoring sarcoidosis disease activity and prognosis.

Cited by 61 publications

References 28 publications

Marked Differences in Tissue-specific Expression of Chitinases in Mouse and Man

Marked Differences in Tissue-specific Expression of Chitinases in Mouse and Man

Chitotriosidase Activity in the Serum of Patients with Sarcoidosis and Pulmonary Tuberculosis

Human CHIT1 gene distribution: new data from Mediterranean and European populations

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