Possible Blood Biomarker Identified for Gaucher Disease Type 1

Possible Blood Biomarker Identified for Gaucher Disease Type 1

Researchers have identified a new marker present in the blood of type 1 Gaucher disease (GD) patients that can potentially be used in disease diagnosis and progression,  according to a study published in the journal FEBS Open Bio.

The study, “Elevation Of Glycoprotein Nonmetastatic Melanoma Protein B In Type 1 Gaucher Disease Patients And Mouse Models,” identified glycoprotein nonmetastatic melanoma protein B (gpNMB) as a potential biomarker for GD.

Although GD is caused by mutations in a single gene (GBA1, which encodes the glucocerebrosidase), patients can have a wide variety of symptom, with either the presence or absence of aggressive neurological disease, making it difficult to link a given mutation to specific symptoms.

Common to all GD variants, however, is the accumulation of a protein, called glucosylceramide, in a type of immune system cell known as macrophages. Rising levels of this protein in macrophages results in their transformation into so-called Gaucher cells, which in turn accumulate in organs such as the spleen, liver, bone marrow or lung, leading to a spectrum of symptoms.

Detecting factors released by Gaucher cells into the blood can help in effectively following Gaucher cell accumulation and disease progression, providing guidance for decisions on therapy initiation and personalized dosing. Previous studies identified the proteins chitotriosidase and CCL18 as markers for Gaucher disease, but these markers do not reflect one particular clinical manifestation of type 1 GD, but rather the total burden of the disease. Also, chitotriosidase cannot always be used, as some individuals present mutations in the corresponding gene.

To identify additional markers of Gaucher cells in patients, researchers investigated the gpNMB protein, whose elevated levels have previously been associated with the disease. The team collected blood samples from 59 type 1 Gaucher patients, ages 15 to 64, and analyzed gpNMB levels prior to and one year after patients started enzyme replacement therapy. Diagnosis of GD was confirmed by demonstration of markedly reduced glucocerebrosidase activity and the presence of a mutant GBA gene. The control group included 20 healthy volunteers.

Results showed that gpNMB was markedly increased in blood samples from the type 1 GD patients, and that the levels of this protein correlated with levels of both chitotriosidase and CCL18, prior and during therapy, which validated the findings about gpNMB. Importantly, changes in Gaucher cell markers in GD patients receiving therapy were shown to accompany comparable corrections in gpNMB levels.

Together, these findings support the use of gpNMB as a potential marker for GD.

“[O]ur finding of markedly elevated plasma gpNMB levels in symptomatic Gaucher patients warrants further investigations regarding its applicability in the clinical management of Gaucher disease as well as its role in the peculiar pathophysiology of the disorder,” the authors concluded.

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