Human Chitotriosidase: A Potential New Marker of Sarcoidosis Severity

Abstract

Sarcoidosis is a multisystemic granulomatous disorder of unknown etiology. The unpredictable clinical course of the disease has prompted research into biomarkers useful for predicting outcome. Among the potential markers of sarcoidosis, a recently proposed indicator was chitotriosidase, a chitinase produced by activated macrophages. Chitotriosidase is involved in the defense against pathogens containing chitin. Increased concentrations of chitotriosidase have been observed in a number of lysosomal storage diseases including Gaucher disease and more recently also in sarcoidosis. In 2004, significantly higher serum chitotriosidase activity was reported for the first time in sarcoidosis patients with respect to controls (p < 0.01); a similar increase was subsequently observed in bronchoalveolar lavage of these patients. In 2007, an increase in enzyme activity was described in juvenile sarcoidosis. Chitotriosidase activity was found to be correlated with angiotensin-converting enzyme levels in serum, radiological stages and quantitative high-resonance CT score for sarcoidosis, suggesting that this enzyme could be a potential marker of disease severity worthy of further study. To evaluate the sensitivity and specificity of this marker, further analysis was done in other granulomatous and diffuse lung diseases. Here, we review the principal literature and the recent evidence of chitotriosidase as a possible marker of sarcoidosis.

Evaluation of CHI3L-1 and CHIT-1 Expression in Differentiated and Polarized Macrophages

“…This discrepancy can reflect a long-range contribution exerted by CHIT-1 operant with macrophage differentiation and polarization. Numerous evidences report the central role of CHIT-1 in the expanding spectrum of disorders ranging from granulomatous disease such as sarcoidosis [20] to a large amount of infections including mycobacterial diseases such as tuberculosis [38] and leprosy [39]. In this contest, a great attention must be given to the fact that these enzymes are produced by differentiated macrophages themselves; they can also damage the host tissues and may be implicate in the progression of a number of chronic inflammatory diseases.…”

“…Subsequently, the levels of this enzyme were found elevated not only in Niemann-Pick disease [18] but also in other pathological conditions including β-thalassemia [19], sarcoidosis [20], multiple sclerosis [21], atherosclerosis [22], and in parasitic infections such as Plasmodium falciparum malaria [23]. Interestingly, other investigations have suggested that CHIT-1 could have a crucial role even in pathological conditions, such as coronary artery disease [24], acute ischemic stroke [25], cerebrovascular dementia, and Alzheimer's disease [26].…”

Established and experimental medical therapy of pulmonary sarcoidosis

“…Chitotriosidase may prove to be a useful marker, but still needs to be evaluated [68]. Proteomic changes have also been reported with treatment with infliximab [34].…”

The puzzling clinical spectrum and course of juvenile sarcoidosis

“…Likewise increased values are obtained in bronchoalveolar lavage. [58] In 2007, an increase in enzyme activity was observed in juvenile sarcoidosis. Chitotriosidase activity was found to be correlated with SACE and lung CT score for sarcoidosis, indicating that this enzyme could be a potential marker of disease severity.…”