Chitotriosidase: a biomarker of activity and severity in patients with sarcoidosis

Abstract

Background: Serum chitotriosidase is a promising biomarker that has shown high specificity and sensitivity in patients with sarcoidosis. The aim of this study was to investigate correlations between serum chitotriosidase, clinical phenotypes, disease localizations and different radiological lung involvement and to identify clinical features associated with over-expression of chitotriosidase in a large cohort of sarcoidosis patients.

Methods: Chitotriosidase activity was evaluated in a population of 694 consecutive patients (males 39%, age 55.8 ± 12.8 years). Clinical and respiratory functional characteristics, Clinical Outcome Scale (COS) classification, clinical phenotypes proposed by the GenPhenResA project, and radiological assessment, including CT scan, were collected. Serum sampling and clinical and functional assessments at follow-up were also included.

Results: Significantly higher chitotriosidase activity was observed in sarcoidosis patients than in healthy controls (p < 0.0001). Evidence of lung fibrosis with reticular abnormalities and traction bronchiectasis at High resolution CT, presence of multiple extrapulmonary sarcoid localizations and increased 24-h urinary excretion of calcium were associated with significantly higher chitotriosidase activity (p < 0.005). Patients with remitted or minimal disease had lower values of chitotriosidase than patients with persistent disease. At follow-up, patients who required an increase in steroid dose showed an increase in its activity.

Conclusions: Chitotriosidase is a reliable biomarker of sarcoidosis. It is increased in patients with sarcoidosis correlating with disease activity, severity and multiorgan dissemination. Steroid therapy tended to reduce chitotriosidase expression, however it responded in cases of disease relapse.

Keywords: Biomarkers; Chitotriosidase; Clinical evaluation; Sarcoidosis.

Fig. 1

Comparison of chitotriosidase activity in steroid-free and treated sarcoidosis patients and healthy controls. Data expressed as mean ± standard deviation. ***: p < 0.0001. One-way ANOVA

Fig. 2

Correlation between chitotriosidase activity and ACE levels in the sarcoidosis cohort (n = 669) (R = 0.3513, p < 0.0001). Pearson’s correlation coefficient

Fig. 3

Comparison of Chitotriosidase activity in Sarcoidosis patients, classified on the basis of the number of extrapulmonary localizations. Data expressed as mean ± standard deviation. **: p < 0.01; ***: p < 0.0001. One-way ANOVA

Fig. 4

Comparison of chitotriosidase activity in different GenPhenResA phenotypes. 1: abdominal; 2: ocular-cardiac-cutaneous-central nervous system; 3: muscoloskeletal-cutaneous; 4: pulmonary; 5: extrapulmonary. Data expressed as mean ± standard deviation. ***: p < 0.0001; *: p < 0.05. One-way ANOVA

Fig. 5

Comparison of chitotriosidase activity in relation to COS classification. Significant differences emerged between COS 1 and COS 5–6–8-9 patients (p < 0.0001 in all cases), COS 2 and COS 5–6-9 patients (p < 0.05, p < 0.05 and p < 0.0001, respectively), COS 4 and COS 5–6–8-9 patients (p < 0.001, p < 0.001, p < 0.05 and p < 0.0001, respectively), COS 5 and COS 7 patients (p < 0.05) and COS 7 and COS 9 patients (p < 0.001). Data expressed as mean ± standard deviation. One-way ANOVA

Fig. 6

Log-rank test comparing outcome (increase in daily dose of steroid) in sarcoidosis patients with basal chitotriosidase above or below the cut-off of 126 nmol/ml/h. (Chi-square = 10.396; p = 0.001). Long rank test

Fig. 7

Line plots of Chitotriosidase activity at basal and follow-up sampling: a therapy modification, improved; b therapy modification, worsened; c therapy modification, stable. *: 0.0012. Paired t test