Chitotriosidase (CHIT1) is an enzyme classified as a chitinase, meaning it breaks down chitin. It is produced and secreted primarily by activated macrophages, which are large white blood cells involved in engulfing foreign particles and cellular debris. High levels of this enzyme in the bloodstream or other bodily fluids reliably indicate persistent, widespread macrophage activation. This heightened activity is a common feature in various conditions, leading to its clinical use as a diagnostic and monitoring tool.
The Biological Role of Chitotriosidase
The function of Chitotriosidase in the human body is related to the immune system. As a chitinase, its ancestral role is to degrade chitin, a structural component found in the cell walls of fungi, the exoskeletons of insects, and the shells of crustaceans. Since humans do not produce chitin, the enzyme’s activity is thought to be a defense mechanism against chitin-containing pathogens, such as certain fungi or parasitic organisms.
The enzyme is produced by macrophages and neutrophils mobilized during an immune response. CHIT1 secretion is triggered by specific immune signals, including interferons and tumor necrosis factor. Therefore, detecting this enzyme signals that the macrophage system is highly active, often in response to inflammation, infection, or the accumulation of materials the body is attempting to clear.
Why Chitotriosidase is Measured
Chitotriosidase is measured because its activity level in the blood acts as a biomarker of macrophage activation and overall inflammatory burden. Since macrophages are central to many chronic diseases, elevated CHIT1 levels reflect disease activity and severity. The enzyme is secreted into the bloodstream, making it easily detectable through a standard blood test that measures its activity using a synthetic substrate.
The enzyme is frequently used to monitor a patient’s response to treatment over time. A decrease in CHIT1 activity generally correlates with successful therapy and reduced disease burden, while an increase can signal disease progression or relapse. Interpretation of results requires caution due to a common genetic variation in the CHIT1 gene. Approximately six percent of the general population is homozygous for a 24-base pair duplication, which results in a complete deficiency of the active enzyme, leading to a false-negative result even in the presence of severe disease. For these individuals, doctors may measure other related biomarkers, such as the chemokine CCL18, to accurately gauge macrophage involvement.
Chitotriosidase in Gaucher Disease
Chitotriosidase measurement is the most sensitive and widely used biochemical marker for Gaucher disease. Gaucher disease is a genetic lysosomal storage disorder caused by a deficiency in the enzyme beta-glucocerebrosidase, leading to the accumulation of glucosylceramide within lysosomes. This accumulation occurs mainly within macrophages, transforming them into large, lipid-laden Gaucher cells that infiltrate organs like the liver and spleen.
These activated Gaucher cells dramatically overproduce and secrete Chitotriosidase into the circulation. In severe cases, serum Chitotriosidase activity can be elevated by as much as 1,000-fold above normal levels. The enzyme’s activity levels correlate strongly with clinical indicators, including the size of the liver and spleen and the severity of bone involvement.
Monitoring Chitotriosidase activity is integral to managing the disease, particularly for tracking the effectiveness of Enzyme Replacement Therapy (ERT). Following the start of ERT, the high CHIT1 levels typically decrease rapidly, often halving within the first eight months of treatment. The continued decline in activity confirms that the therapy is successfully reducing the Gaucher cell burden and overall disease activity.
Chitotriosidase in Other Health Conditions
While it is the primary biochemical marker for Gaucher disease, elevated Chitotriosidase activity is also observed in a range of other chronic inflammatory and storage disorders, reflecting generalized macrophage activity. This includes other lysosomal storage disorders, such as Niemann-Pick disease and certain types of gangliosidosis. In these cases, the accumulation of different substances within macrophages triggers the overproduction of CHIT1.
High levels are consistently found in patients with Sarcoidosis, a disease characterized by the formation of inflammatory masses called granulomas. The enzyme’s activity in sarcoidosis often correlates with the extent and severity of the disease, and it can decrease following treatment with corticosteroids. Elevated CHIT1 has also been noted in chronic conditions like Thalassemia, where macrophage activity is heightened due to the clearance of damaged red blood cells. It is also elevated in some parasitic infections, such as malaria. In all these other conditions, Chitotriosidase functions as a supportive marker of disease activity and macrophage involvement, though it is not typically considered the definitive diagnostic marker as it is in Gaucher disease.