Human chitotriosidase: a sensitive biomarker of sarcoidosis

J Clin Immunol. 2013 Jan;33(1):264-70. doi: 10.1007/s10875-012-9754-4. Epub 2012 Aug 10.

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.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • Female
  • Follow-Up Studies
  • Hexosaminidases / blood
  • Hexosaminidases / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / blood
  • Peptidyl-Dipeptidase A / metabolism
  • Phenotype
  • Prognosis
  • Reproducibility of Results
  • Sarcoidosis / diagnosis*
  • Sarcoidosis / enzymology*
  • Sarcoidosis / immunology
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Biomarkers
  • Hexosaminidases
  • chitotriosidase
  • Peptidyl-Dipeptidase A