Chitotriosidase is a protein in the human body that functions as an enzyme, meaning it helps speed up specific chemical reactions. It is classified as a glycosyl hydrolase, belonging to the family 18 glycosylases. This enzyme is naturally present in both healthy individuals and those with various medical conditions.
Biological Function and Origin
The primary biological function of chitotriosidase is its ability to break down chitin, a complex sugar molecule found in the exoskeletons of insects and the cell walls of fungi. While humans do not naturally produce chitin, this enzyme represents an evolutionarily conserved defense mechanism against chitin-containing pathogens like fungi and parasites. Chitotriosidase is predominantly produced and secreted by specialized immune cells known as activated macrophages and neutrophils. These macrophages become highly active during acute and chronic inflammatory conditions, leading to increased chitotriosidase enzyme activity.
Chitotriosidase as a Disease Biomarker
Chitotriosidase levels are measured clinically because their elevation indicates increased macrophage activity associated with various diseases. It is an important biomarker for Gaucher disease, a lysosomal storage disorder where specific lipids accumulate in macrophages. In these patients, levels can be hundreds to a thousand-fold higher than normal, making it useful for both diagnosing the condition and monitoring treatment effectiveness. Elevated levels are also observed in other conditions where macrophage activation is a prominent feature, including Niemann-Pick disease, sarcoidosis (a disorder characterized by inflammatory cell clusters), and certain fungal infections. The enzyme’s levels can also be elevated in conditions like chronic obstructive pulmonary disease (COPD), atherosclerosis, and some cancers.
Testing and Interpreting Levels
Chitotriosidase levels are measured through a blood test, specifically from a serum or plasma sample. A “normal” range for chitotriosidase activity is generally considered to be below 80-90 nmol/h/mL in healthy individuals, though variations exist depending on age and laboratory methods. Elevated levels suggest increased macrophage activity, indicating underlying conditions like lysosomal storage disorders or inflammatory diseases. This test is performed as part of a broader diagnostic evaluation and should not be interpreted in isolation. For conditions like Gaucher disease, monitoring levels over time helps assess disease progression or treatment effectiveness, with a decrease often indicating a positive response.
Genetic Influences on Chitotriosidase Activity
Specific genetic variations, known as polymorphisms, in the CHIT1 gene can influence chitotriosidase activity. A common polymorphism involves a 24-base pair duplication in exon 10 of the CHIT1 gene, which can lead to reduced or completely absent enzyme activity. Approximately 6% of the Caucasian population may be homozygous for this duplication, meaning they have two copies of the altered gene and thus lack chitotriosidase activity. This genetic deficiency is important to consider when interpreting test results, as a low or absent level might be due to this genetic factor rather than a lack of disease activity. Genetic testing can confirm these polymorphisms.