Skip to main content
Erschienen in: Journal of Clinical Immunology 1/2013

01.01.2013 | Original Research

Human Chitotriosidase: a Sensitive Biomarker of Sarcoidosis

verfasst von: Elena Bargagli, David Bennett, Claudia Maggiorelli, Pasquale Di Sipio, Maria Margollicci, Nicola Bianchi, Paola Rottoli

Erschienen in: Journal of Clinical Immunology | Ausgabe 1/2013

Einloggen, um Zugang zu erhalten

Abstract

Background

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. No suitable biomarkers are available to evaluate the evolution of this disease, which still has an unpredictable clinical course. Some years ago our research group proposed chitotriosidase as a potential biomarker with prognostic value, that however needed to be validated.

Aims and methods

The aims of this study were to evaluate the sensitivity and specificity of chitotriosidase in a population of 232 sarcoidosis patients under the observation of our Sarcoidosis Regional Referral Centre in Siena and to analyse enzyme concentrations in different disease phenotypes (as defined by the recently published COS classification) to define its prognostic value.

Results

Serum chitotriosidase concentrations were significantly higher in patients than in healthy controls (p < 0.0001) and were directly correlated with ACE levels (r = 0.25, p < 0.0001). ROC curve analysis revealed 88.6 % sensitivity and 92.8 % specificity. Enzyme concentrations were significantly higher in stage 3 sarcoidosis than in stage 0 (p = 0.02). The lowest concentrations of chitotriosidase were found in untreated patients in remission (COS-1), while the highest enzyme concentrations were found in symptomatic patients with persistent disease on steroids and with functional deterioration in the last year (COS-9). In COS-9 subgroup, chitotriosidase decreased significantly after the increasing of steroid dose or the introduction of a new immunosuppressant therapy (p < 0.01).

Conclusion

Chitotriosidase proved to be a biomarker with good sensitivity and specificity that is easily detected in serum. It can be proposed in clinical practice to identify progressive patients requiring close follow-up, to detect relapses and to evaluate the effects of therapy.
Literatur
1.
Zurück zum Zitat Hunninghake GW, Costabel U, Ando M, et al. ATS/ERS/WASOG statement on sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16:149–73.PubMed Hunninghake GW, Costabel U, Ando M, et al. ATS/ERS/WASOG statement on sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16:149–73.PubMed
2.
Zurück zum Zitat Yamamoto M, Sharma OP, Hosoda Y. Special report: the 1991 descriptive definition of sarcoidosis. Sardoidosis. 1992;9:33–4. Yamamoto M, Sharma OP, Hosoda Y. Special report: the 1991 descriptive definition of sarcoidosis. Sardoidosis. 1992;9:33–4.
3.
Zurück zum Zitat Agostini C, Trentin L, Facco M, et al. Role of IL-15, IL-2, and their receptors in the development of T cell alveolitis in pulmonary sarcoidosis. J Immunol. 1996;157:910–8.PubMed Agostini C, Trentin L, Facco M, et al. Role of IL-15, IL-2, and their receptors in the development of T cell alveolitis in pulmonary sarcoidosis. J Immunol. 1996;157:910–8.PubMed
4.
Zurück zum Zitat Agostini C, Semenzato G. Cytokines in sarcoidosis. Semin Respir Infect. 1998;13:184–96.PubMed Agostini C, Semenzato G. Cytokines in sarcoidosis. Semin Respir Infect. 1998;13:184–96.PubMed
5.
Zurück zum Zitat Prior C, Knight RA, Herold M. Pulmonary sarcoidosis: patterns of cytokine release in vitro. Eur Respir J. 1996;9:47–53.PubMedCrossRef Prior C, Knight RA, Herold M. Pulmonary sarcoidosis: patterns of cytokine release in vitro. Eur Respir J. 1996;9:47–53.PubMedCrossRef
6.
Zurück zum Zitat Gurrieri C, Bortoli M, Brunetta E, et al. Cytokines, chemokines and other biomolecular markers in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2005;22 Suppl 1:S9–S14.PubMed Gurrieri C, Bortoli M, Brunetta E, et al. Cytokines, chemokines and other biomolecular markers in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2005;22 Suppl 1:S9–S14.PubMed
8.
9.
Zurück zum Zitat Judson MA, Baughman RP, Thompson BW, et al. Two years prognosis of sarcoidosis: the ACCESS experience. Sarcoidosis Vasc Diffuse Lung Dis. 2003;20:204–11.PubMed Judson MA, Baughman RP, Thompson BW, et al. Two years prognosis of sarcoidosis: the ACCESS experience. Sarcoidosis Vasc Diffuse Lung Dis. 2003;20:204–11.PubMed
10.
Zurück zum Zitat Corte TJ, Wells AU, Nicholson AG, et al. Pulmonary hypertension in sarcoidosis: a review. Respirology. 2011;16:69–77.PubMedCrossRef Corte TJ, Wells AU, Nicholson AG, et al. Pulmonary hypertension in sarcoidosis: a review. Respirology. 2011;16:69–77.PubMedCrossRef
11.
Zurück zum Zitat Ziegenhagen MW, Rothe ME, Schlaak M, et al. BAL and sierological parameters reflecting the severity of sarcoidosis. Eur Respir J. 2003;21:407–13.PubMedCrossRef Ziegenhagen MW, Rothe ME, Schlaak M, et al. BAL and sierological parameters reflecting the severity of sarcoidosis. Eur Respir J. 2003;21:407–13.PubMedCrossRef
12.
Zurück zum Zitat Hunninghake GW, Gilbert S, Pueringer R, et al. Outcome of the treatment of sarcoidosis. Am J Respir Crit Care Med. 1994;149:893–8.PubMed Hunninghake GW, Gilbert S, Pueringer R, et al. Outcome of the treatment of sarcoidosis. Am J Respir Crit Care Med. 1994;149:893–8.PubMed
13.
14.
Zurück zum Zitat Prasse A, Katic C, et al. Phenotyping sarcoidosis from a pulmonary perspective. Am J Respir Crit Care Med. 2008;177:330–6.PubMedCrossRef Prasse A, Katic C, et al. Phenotyping sarcoidosis from a pulmonary perspective. Am J Respir Crit Care Med. 2008;177:330–6.PubMedCrossRef
15.
Zurück zum Zitat Baughman RP, Nagai S, et al. Defining the clinical outcome status (COS) in sarcoidosis: results of WASOG Task Force. Sarcoidosis Vasc Diffuse Lung Dis. 2011;28:56–64.PubMed Baughman RP, Nagai S, et al. Defining the clinical outcome status (COS) in sarcoidosis: results of WASOG Task Force. Sarcoidosis Vasc Diffuse Lung Dis. 2011;28:56–64.PubMed
16.
Zurück zum Zitat Bargagli E, Mazzi A, Rottoli P. Markers of inflammation in sarcoidosis: blood, urine, BAL, sputum and exhaled gas. Clin Chest Med. 2008;29:445–58.PubMedCrossRef Bargagli E, Mazzi A, Rottoli P. Markers of inflammation in sarcoidosis: blood, urine, BAL, sputum and exhaled gas. Clin Chest Med. 2008;29:445–58.PubMedCrossRef
17.
Zurück zum Zitat Scadding JG. Prognosis of intrathoracic sarcoidosis in England: a review of 136 cases after five years' observation. BMJ. 1961;2:1165–72.PubMedCrossRef Scadding JG. Prognosis of intrathoracic sarcoidosis in England: a review of 136 cases after five years' observation. BMJ. 1961;2:1165–72.PubMedCrossRef
18.
Zurück zum Zitat Boot RG, Renkema GH, Verhoek M, et al. The human chitotriosidase gene. Nature of inherited enzyme deficiency. J Biol Chem. 1998;273:25680–5.PubMedCrossRef Boot RG, Renkema GH, Verhoek M, et al. The human chitotriosidase gene. Nature of inherited enzyme deficiency. J Biol Chem. 1998;273:25680–5.PubMedCrossRef
19.
Zurück zum Zitat Michelakakis H, Dimitriou E, Labadaridis I. The expanding spectrum of disorders with elevated plasma chitotriosidase activity: an update. J Inherit Metab Dis. 2004;27:705–6.PubMedCrossRef Michelakakis H, Dimitriou E, Labadaridis I. The expanding spectrum of disorders with elevated plasma chitotriosidase activity: an update. J Inherit Metab Dis. 2004;27:705–6.PubMedCrossRef
20.
Zurück zum Zitat Altarescu G, Rudensky B, Abrahamov A, et al. Plasma chitotriosidase activity in patients with beta-thalassemia. Am J Hematol. 2003;72:285–6. Altarescu G, Rudensky B, Abrahamov A, et al. Plasma chitotriosidase activity in patients with beta-thalassemia. Am J Hematol. 2003;72:285–6.
21.
Zurück zum Zitat Barone R, Simpore J, Malaguarnera L, et al. Plasma chitotriosidase activity in acute Plasmodium falciparum malaria. Clin Chim Acta. 2003;331:79–85.PubMedCrossRef Barone R, Simpore J, Malaguarnera L, et al. Plasma chitotriosidase activity in acute Plasmodium falciparum malaria. Clin Chim Acta. 2003;331:79–85.PubMedCrossRef
22.
Zurück zum Zitat Rottoli P, Magi B, Perari MG, et al. Cytokine profile and proteome analysis in BAL of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis and idiopathic pulmonary fibrosis. Proteomics. 2005;5:1423–30.PubMedCrossRef Rottoli P, Magi B, Perari MG, et al. Cytokine profile and proteome analysis in BAL of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis and idiopathic pulmonary fibrosis. Proteomics. 2005;5:1423–30.PubMedCrossRef
23.
Zurück zum Zitat Aguilera B, Ghauharali-Van der Vlugt K, Helmond MT, et al. Transglycosidase activity of chitotriosidase: improved enzymatic assay for the human macrophage chitinase. J Biol Chem. 2003;278:40911–6.PubMedCrossRef Aguilera B, Ghauharali-Van der Vlugt K, Helmond MT, et al. Transglycosidase activity of chitotriosidase: improved enzymatic assay for the human macrophage chitinase. J Biol Chem. 2003;278:40911–6.PubMedCrossRef
24.
Zurück zum Zitat Grosso S, Margollicci MA, Bargagli E, et al. Serum levels of chitotriosidase as a marker of disease activity and clinical stage in sarcoidosis. Scand J Clin Lab Invest. 2004;64:57–62.PubMedCrossRef Grosso S, Margollicci MA, Bargagli E, et al. Serum levels of chitotriosidase as a marker of disease activity and clinical stage in sarcoidosis. Scand J Clin Lab Invest. 2004;64:57–62.PubMedCrossRef
25.
Zurück zum Zitat Bargagli E, Margollicci MA, Perrone A, et al. Chitotriosidase analysis in bronchoalveolar lavage of patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2007;24:59–64.PubMed Bargagli E, Margollicci MA, Perrone A, et al. Chitotriosidase analysis in bronchoalveolar lavage of patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2007;24:59–64.PubMed
26.
Zurück zum Zitat Rothkranz-Kos S, van Dieijen-Visser MP, Mulder PG, et al. Potential usefulness of infiammatory markers to monitor respiratory functional impairment in sarcoidosis. Clin Chem. 2003;49:1510–7.CrossRef Rothkranz-Kos S, van Dieijen-Visser MP, Mulder PG, et al. Potential usefulness of infiammatory markers to monitor respiratory functional impairment in sarcoidosis. Clin Chem. 2003;49:1510–7.CrossRef
27.
Zurück zum Zitat Bargagli E, Margollicci M, Luddi A, et al. Chitotriosidase activity in patients with interstitial lung diseases. Resp Med. 2007;101:2176–81.CrossRef Bargagli E, Margollicci M, Luddi A, et al. Chitotriosidase activity in patients with interstitial lung diseases. Resp Med. 2007;101:2176–81.CrossRef
28.
Zurück zum Zitat Bargagli E, Margollicci M, Nikiforakis N, et al. Chitotriosidase activity in the serum of patients with sarcoidosis and pulmonary tuberculosis. Respiration. 2007;74(5):548–52.PubMedCrossRef Bargagli E, Margollicci M, Nikiforakis N, et al. Chitotriosidase activity in the serum of patients with sarcoidosis and pulmonary tuberculosis. Respiration. 2007;74(5):548–52.PubMedCrossRef
29.
Zurück zum Zitat Tercelj W, Salobir B, Siwcic S, et al. Chitotriosidase activity in sarcoidosis and some other pulmonary diseases. Scand J Clin Lab Invest. 2009;69:575–8.PubMedCrossRef Tercelj W, Salobir B, Siwcic S, et al. Chitotriosidase activity in sarcoidosis and some other pulmonary diseases. Scand J Clin Lab Invest. 2009;69:575–8.PubMedCrossRef
30.
Zurück zum Zitat Brunner J, Scholl-Bürgi S, Zimmerhackl LB. Chitotriosidase as a marker of disease activity in sarcoidosis. Rheumatol Int. 2007;27:1171–2.PubMedCrossRef Brunner J, Scholl-Bürgi S, Zimmerhackl LB. Chitotriosidase as a marker of disease activity in sarcoidosis. Rheumatol Int. 2007;27:1171–2.PubMedCrossRef
31.
Zurück zum Zitat Newman LS, Rose CS, Bresnitz EA, and the ACCESS Research Group. A case-control etiological study of sarcoidosis-environmental and occupational risk factors. Am J Crit Care Med. 2004;170:1324–30.CrossRef Newman LS, Rose CS, Bresnitz EA, and the ACCESS Research Group. A case-control etiological study of sarcoidosis-environmental and occupational risk factors. Am J Crit Care Med. 2004;170:1324–30.CrossRef
32.
Zurück zum Zitat Tercelj M, Stopincek S, Salobir B, et al. In vitro and in vivo reactivity to fungal cell wall agents in sarcoidosis. Clin Exp Immunol. 2011;166:87–93.PubMedCrossRef Tercelj M, Stopincek S, Salobir B, et al. In vitro and in vivo reactivity to fungal cell wall agents in sarcoidosis. Clin Exp Immunol. 2011;166:87–93.PubMedCrossRef
33.
Zurück zum Zitat Tercelj M, Salobir B, Zupancic M, Rylander R. Antifungal medication is efficient in the treatment of sarcoidosis. Ther Adv Respir Dis. 2011;5(3):157–62.PubMedCrossRef Tercelj M, Salobir B, Zupancic M, Rylander R. Antifungal medication is efficient in the treatment of sarcoidosis. Ther Adv Respir Dis. 2011;5(3):157–62.PubMedCrossRef
34.
Zurück zum Zitat Tercelj M, Rott T, Rylander R. Antifungal treatment in sarcoidosis- a pilot intervention trial. Resp Med. 2007;101:774–8.CrossRef Tercelj M, Rott T, Rylander R. Antifungal treatment in sarcoidosis- a pilot intervention trial. Resp Med. 2007;101:774–8.CrossRef
35.
Zurück zum Zitat Miyoshi S, Hamada H, Kadowaki T, et al. Comparative evaluation of serum markers in pulmonary sarcoidosis. Chest. 2010;137:1391–7.PubMedCrossRef Miyoshi S, Hamada H, Kadowaki T, et al. Comparative evaluation of serum markers in pulmonary sarcoidosis. Chest. 2010;137:1391–7.PubMedCrossRef
36.
Zurück zum Zitat Tzouvelekis A, Kouliatsis G, Anevlavis S, et al. Serum biomarkers in interstitial lung diseases. Respir Res. 2005;6:78.PubMedCrossRef Tzouvelekis A, Kouliatsis G, Anevlavis S, et al. Serum biomarkers in interstitial lung diseases. Respir Res. 2005;6:78.PubMedCrossRef
37.
Zurück zum Zitat Hunninghake GW, Bedell GN, Zavala DC, et al. Role of interleukin-2 release by lung T-cells in active pulmonary sarcoidosis. Am Rev Respir Dis. 1983;128:634–8.PubMed Hunninghake GW, Bedell GN, Zavala DC, et al. Role of interleukin-2 release by lung T-cells in active pulmonary sarcoidosis. Am Rev Respir Dis. 1983;128:634–8.PubMed
38.
Zurück zum Zitat Prior C, Barbee RA, Evans PM, et al. Lavage versus serum measurements of lysozyme, angiotensin converting enzyme and other inflammatory markers in pulmonary sarcoidosis. Eur Respir J. 1990;3:1146–54.PubMed Prior C, Barbee RA, Evans PM, et al. Lavage versus serum measurements of lysozyme, angiotensin converting enzyme and other inflammatory markers in pulmonary sarcoidosis. Eur Respir J. 1990;3:1146–54.PubMed
Metadaten
Titel
Human Chitotriosidase: a Sensitive Biomarker of Sarcoidosis
verfasst von
Elena Bargagli
David Bennett
Claudia Maggiorelli
Pasquale Di Sipio
Maria Margollicci
Nicola Bianchi
Paola Rottoli
Publikationsdatum
01.01.2013
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 1/2013
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-012-9754-4

Weitere Artikel der Ausgabe 1/2013

Journal of Clinical Immunology 1/2013 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Battle of Experts: Sport vs. Spritze bei Adipositas und Typ-2-Diabetes

11.05.2024 DDG-Jahrestagung 2024 Kongressbericht

Im Battle of Experts traten zwei Experten auf dem Diabeteskongress gegeneinander an: Die eine vertrat die Auffassung „Sport statt Spritze“ bei Adipositas und Typ-2-Diabetes, der andere forderte „Spritze statt Sport!“ Am Ende waren sie sich aber einig: Die Kombination aus beidem erzielt die besten Ergebnisse.

Triglyzeridsenker schützt nicht nur Hochrisikopatienten

10.05.2024 Hypercholesterinämie Nachrichten

Patienten mit Arteriosklerose-bedingten kardiovaskulären Erkrankungen, die trotz Statineinnahme zu hohe Triglyzeridspiegel haben, profitieren von einer Behandlung mit Icosapent-Ethyl, und zwar unabhängig vom individuellen Risikoprofil.

Gibt es eine Wende bei den bioresorbierbaren Gefäßstützen?

In den USA ist erstmals eine bioresorbierbare Gefäßstütze – auch Scaffold genannt – zur Rekanalisation infrapoplitealer Arterien bei schwerer PAVK zugelassen worden. Das markiert einen Wendepunkt in der Geschichte dieser speziellen Gefäßstützen.

Vorsicht, erhöhte Blutungsgefahr nach PCI!

10.05.2024 Koronare Herzerkrankung Nachrichten

Nach PCI besteht ein erhöhtes Blutungsrisiko, wenn die Behandelten eine verminderte linksventrikuläre Ejektionsfraktion aufweisen. Das Risiko ist umso höher, je stärker die Pumpfunktion eingeschränkt ist.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.