Hum Immunol. 2025 Apr 03. pii: S0198-8859(25)00073-4. [Epub ahead of print]86(3): 111302
INTRODUCTION: Gaucher disease (GD) is a rare lysosomal storage disease caused by mutations in the Glucocerebrosidase (GBA) gene. The innate immunopathology of GD beyond macrophage involvement is not well characterized. In the current study, the changes in ILC subsets, γδ T and MAIT cells, TNF-α and IFN-γ cytokine levels in the peripheral blood of patients with Type 1 GD and GD carriers were evaluated.
METHODS: Peripheral blood mononuclear cells obtained from patients and controls were isolated using the Ficoll-Paque gradient method; after surface and intracellular staining, the cells were analyzed on FACSARIA III.
RESULTS: Our analyses revealed that CD8+ MAIT cells and CD8+ γδ T cells are reduced in the treated patients compared with the carriers. MAIT cell-specific IFN-γ production and absolute counts of IFN-γ+ MAIT cells significantly decreased in Type 1 GD patients who received ERT compared with healthy controls, which could be important indicators for the pathogenesis and severity of the disease. Additionally, total ILCs, particularly the ILC1 subset, were reduced in the Type I GD patients receiving ERT compared with healthy controls and the carriers.
CONCLUSION: The changes observed in ILCs, γδ T cells, MAIT cells, TNF-α and IFN-γ cytokine levels in both pre- and post-treatment Type 1 GD patients may play a vital role in the pathogenesis of GD.
Keywords: Cytokines; Gaucher disease; ILC cells; MAIT cells; γδ T cells