Skip to main content

Advertisement

Log in

Human Chitotriosidase: a Sensitive Biomarker of Sarcoidosis

  • Original Research
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

BAL:

bronchoalveolar lavage

ACE:

angiotensin converting enzyme

References

  1. Hunninghake GW, Costabel U, Ando M, et al. ATS/ERS/WASOG statement on sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16:149–73.

    PubMed  CAS  Google Scholar 

  2. Yamamoto M, Sharma OP, Hosoda Y. Special report: the 1991 descriptive definition of sarcoidosis. Sardoidosis. 1992;9:33–4.

    Google Scholar 

  3. 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  CAS  Google Scholar 

  4. Agostini C, Semenzato G. Cytokines in sarcoidosis. Semin Respir Infect. 1998;13:184–96.

    PubMed  CAS  Google Scholar 

  5. Prior C, Knight RA, Herold M. Pulmonary sarcoidosis: patterns of cytokine release in vitro. Eur Respir J. 1996;9:47–53.

    Article  PubMed  CAS  Google Scholar 

  6. 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  Google Scholar 

  7. Baudin B. ACE for sarcoidosis diagnosis. Pathol Biol. 2005;53:183–8.

    Article  PubMed  CAS  Google Scholar 

  8. Lynch JP, Kazerooni EA, Gay SE. Pulmonary sarcoidosis. Clin Chest Med. 1997;18:755–85.

    Article  PubMed  Google Scholar 

  9. 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  Google Scholar 

  10. Corte TJ, Wells AU, Nicholson AG, et al. Pulmonary hypertension in sarcoidosis: a review. Respirology. 2011;16:69–77.

    Article  PubMed  Google Scholar 

  11. Ziegenhagen MW, Rothe ME, Schlaak M, et al. BAL and sierological parameters reflecting the severity of sarcoidosis. Eur Respir J. 2003;21:407–13.

    Article  PubMed  CAS  Google Scholar 

  12. 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  CAS  Google Scholar 

  13. Wasfi YS, Rose CS. A new tool to assess sarcoidosis severity. Chest. 2006;129:1234–45.

    Article  PubMed  Google Scholar 

  14. Prasse A, Katic C, et al. Phenotyping sarcoidosis from a pulmonary perspective. Am J Respir Crit Care Med. 2008;177:330–6.

    Article  PubMed  CAS  Google Scholar 

  15. 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  CAS  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. Scadding JG. Prognosis of intrathoracic sarcoidosis in England: a review of 136 cases after five years' observation. BMJ. 1961;2:1165–72.

    Article  PubMed  CAS  Google Scholar 

  18. Boot RG, Renkema GH, Verhoek M, et al. The human chitotriosidase gene. Nature of inherited enzyme deficiency. J Biol Chem. 1998;273:25680–5.

    Article  PubMed  CAS  Google Scholar 

  19. 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.

    Article  PubMed  CAS  Google Scholar 

  20. Altarescu G, Rudensky B, Abrahamov A, et al. Plasma chitotriosidase activity in patients with beta-thalassemia. Am J Hematol. 2003;72:285–6.

    Google Scholar 

  21. Barone R, Simpore J, Malaguarnera L, et al. Plasma chitotriosidase activity in acute Plasmodium falciparum malaria. Clin Chim Acta. 2003;331:79–85.

    Article  PubMed  CAS  Google Scholar 

  22. 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.

    Article  PubMed  CAS  Google Scholar 

  23. 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.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    Article  PubMed  CAS  Google Scholar 

  25. 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  Google Scholar 

  26. 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.

    Article  Google Scholar 

  27. Bargagli E, Margollicci M, Luddi A, et al. Chitotriosidase activity in patients with interstitial lung diseases. Resp Med. 2007;101:2176–81.

    Article  Google Scholar 

  28. 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.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    Article  PubMed  CAS  Google Scholar 

  30. Brunner J, Scholl-Bürgi S, Zimmerhackl LB. Chitotriosidase as a marker of disease activity in sarcoidosis. Rheumatol Int. 2007;27:1171–2.

    Article  PubMed  CAS  Google Scholar 

  31. 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.

    Article  Google Scholar 

  32. 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.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    Article  PubMed  CAS  Google Scholar 

  34. Tercelj M, Rott T, Rylander R. Antifungal treatment in sarcoidosis- a pilot intervention trial. Resp Med. 2007;101:774–8.

    Article  Google Scholar 

  35. Miyoshi S, Hamada H, Kadowaki T, et al. Comparative evaluation of serum markers in pulmonary sarcoidosis. Chest. 2010;137:1391–7.

    Article  PubMed  CAS  Google Scholar 

  36. Tzouvelekis A, Kouliatsis G, Anevlavis S, et al. Serum biomarkers in interstitial lung diseases. Respir Res. 2005;6:78.

    Article  PubMed  Google Scholar 

  37. 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  CAS  Google Scholar 

  38. 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  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elena Bargagli.

Additional information

All the authors have no conflict of interest to declare

The present work was performed at Department of Clinical Medicine and Immunology Respiratory Disease Section, no funding sponsors to declare.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bargagli, E., Bennett, D., Maggiorelli, C. et al. Human Chitotriosidase: a Sensitive Biomarker of Sarcoidosis. J Clin Immunol 33, 264–270 (2013). https://doi.org/10.1007/s10875-012-9754-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-012-9754-4

Keywords

Navigation