Enzyme replacement therapy (ERT) was associated with decreased levels of inflammatory mediators in a group of patients with Gaucher disease (GD) type 1.
The study “Could enzyme replacement therapy promote immune tolerance in Gaucher disease type 1?” was published in the journal Blood Cells, Molecules & Diseases.
GD was the first lysosomal storage disorder to be effectively treated with ERT, a treatment that works by supplementing or replacing the Gaucher patient’s missing or deficient enzyme, beta-glucocerebrosidase.
In previous studies, however, researchers have highlighted concerns that patients treated with this type of therapy may develop alterations in their immune responses that target the enzyme being infused. These changes usually manifest as hypersensitivity reactions and antibodies to the replacement protein (loss of immune tolerance).
In this study, researchers set out to study how ERT affects patients’ immune responses, as the impact of ERT on the immune system of GD patients and ideal therapy dosing have not been thoroughly investigated.
To this end, they compared the levels of immune signaling molecules, cytokines and chemokines, in patients with GD treated with ERT at different dosages and with different treatment durations.
In total, they measured the levels of inflammatory cytokines and chemokines in blood samples from 31 patients with established diagnosis of GD type 1. Specifically, they measured the levels of three different cytokines – interleukin (IL)-6, Tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma; and three chemokines – IL-8, monocyte chemoattractant protein-1 (MCP-1), and IFN-gamma-inducible protein 10 (IP-10).
According to ERT duration, researchers divided patients into two groups – group 1 was treated for longer and at higher doses than group 2.
Participants in group 1 showed statistically significant lower levels of several cytokines and chemokines, specifically IL-6, TNF-alpha, IFN-gamma, IL-8, IP-10, and MCP-1, when compared to those in group 2.
Researchers observed no other differences in hematological parameters, including levels of hemoglobin, and numbers of platelets and leukocyte (two important cell components of our immune system). Additionally, patients from both groups presented no differences in clinical outcomes.
Researchers suggest that dosage and duration of treatment may be related to the development of immune tolerance. However, despite the differences in the concentration of inflammatory mediators, the effectiveness of ERT appears to be independent on the dosages administered and duration of treatment.
However, “Despite the efficacy of ERT in terms of clinical improvement, a greater understanding of the immune mechanisms involved in this treatment modality for lysosomal storage disorders is still needed, as there have been reports of potential effects of enzyme infusion on the immune system,” researchers concluded.
