The study, “Accuracy of chitotriosidase activity and CCL18 concentration in assessing type I Gaucher disease severity. A systematic review with meta-analysis of individual participant data,” was published in the journal Haemotologica.
Gaucher disease is caused by a mutation in the GBA gene, which leads to abnormal production of the enzyme beta-glucocerebrosidase. This results in accumulation of a fatty substance called glucocerebroside inside immune cells called macrophages, which then become Gaucher cells.
The course of Gaucher is difficult to predict, and for that reason, scientists and physicians have been working to identify biomarkers that could be used to assess disease activity and severity.
The activity of the enzyme chitotriosidase is one of the biomarkers that has been proposed to monitor disease activity. This enzyme is produced by Gaucher cells, and its activity levels correlate with typical Gaucher manifestations, such as low platelet counts, and liver and spleen enlargement.
Yet, measuring chitotriosidase is technically complex and not standardized across laboratories, the researchers said.
Levels of the cytokine CCL18 in the blood have also been proposed as a biomarker for Gaucher. A cytokine is a molecule that regulates immune and inflammatory response.
Like chitotriosidase, CCL18 is also produced by Gaucher cells, and its higher concentration in the blood of people with Gaucher compared to the general population has been correlated with several signs and symptoms of the disease.
Although both have been used interchangeably as biomarkers of disease activity and severity, few studies have compared the accuracy between these biomarkers.
To address this gap, an international team performed a meta-analysis (a statistical analysis pooling data from multiple studies) to assess the accuracy of chitotriosidase and CCL18 in predicting disease severity in patients with type 1 Gaucher, the most common form of the disease.
The researchers used three online databases — Medline, Embase, and CENTRAL — to search for relevant studies published from 1995 t0 2017. Nine studies had data on individual participants. Ultimately, the analysis included 334 patients with type 1 Gaucher.
Patients were considered to have severe disease when their liver volume was at least 1.25-times higher than normal, spleen volume was at least 5-times higher than normal, hemoglobin levels were under 11 g/dL (normal range 12.0 to 17.5 g/dL), and platelet counts were under 100 x 109/L (normal range 150-450 x 109/L).
Results revealed that, taken collectively as a compound primary outcome, these parameters were associated with a 5.3-fold increase in the mean activity levels of chitotriosidase, and with a 3.0-fold increase in the levels of CCL18 in the blood.
The accuracy of both biomarkers at distinguishing patients who met all criteria of severe disease were similar (0.82 for chitotriosidase activity and 0.84 for CCL18 levels). Combining the two biomarkers did not surpass the accuracy of CCL18 alone.
These estimates remained consistent in separate analyses of each included study, and across different age and treatment groups.
“In conclusion, CCL18 concentration is as accurate as chitotriosidase activity in assessing hematological [blood] and visceral parameters of GD [Gaucher disease] severity and can be measured in all GD patients,” the researchers wrote.
“This meta-analysis supports the use of CCL18 rather than chitotriosidase activity for monitoring GD activity in routine practice,” they added.
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