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Could enzyme replacement therapy promote immune tolerance in Gaucher disease type 1?
Blood Cells, Molecules & Diseases 2018 Februrary
Among the lysosomal storage disorders, Gaucher disease (GD) features some of the most striking alterations in the immune system, including increased levels of cytokines and chemokines. Although studies have demonstrated the efficacy of enzyme replacement therapy (ERT) for GD, the ideal dosage remains controversial. In this study, we report differences in levels of cytokines (IL-6, TNF-a, and IFN-y) and chemokines (IL-8, IP-10, and MCP-1) in patients with GD type 1 treated with different ERT dosages and treatment durations. Patients were recruited from two ERT centers in Brazil and divided into two groups according to treatment facility. Comparison between groups showed that patients in group 1 had received ERT for longer (p=0.0078) and at higher doses (p=0.0002) than those in group 2. Patients in group 1 exhibited decreased levels of IL-6 (p=0.0006), TNF-α (p<0.0001), IFN-γ (p<0.0001), IL-8 (p=0.0083), IP-10 (p<0.0001), and MCP-1 (p<0.0001) when compared to patients in group 2. Otherwise, patients in both groups were clinically similar, with no differences in hemoglobin, platelet, or leukocyte counts. Our data suggest that in GD type 1 the dosage and duration of therapy may be associated with establishment of peripheral tolerance and, consequently, decreased serum levels of inflammatory cytokines and chemokines.
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