Leukocyte Imbalances in Mucopolysaccharidoses Patients

Mucopolysaccharidoses (MPSs) are rare inherited lysosomal storage diseases (LSDs) caused by deficient activity in one of the enzymes responsible for glycosaminoglycans lysosomal degradation. MPS II is caused by pathogenic mutations in the IDS gene, leading to deficient activity of the enzyme iduronate-2-sulfatase, which causes dermatan and heparan sulfate storage in the lysosomes. MPS VI has dermatan sulfate lysosomal storage, owing to a deficiency of arylsulfatase B, due to pathogenic mutations in the ARSB gene. Alterations in the immune system of MPSs mouse models have been described but the data is still scarce concerning MPSs patients. Herein, we study different leukocyte populations in MPS II and VI disease patients. MPS VI, but not MPS II patients, have a decrease percentage of Natural Killer (NK) cells and monocytes when compared with controls. No alterations were identified in the percentage of T, invariant NKT and B cells in both groups of MPS disease patients. However, we uncovered alterations in the naïve versus memory status of both helper and cytotoxic T cells in MPS VI disease patients compared to control group. Indeed, MPS VI disease patients have a higher frequency of naïve T cells and consequently lower frequency of memory T cells than control subjects. Altogether, these results reveal MPS VI disease-specific alterations in some leukocyte populations, suggesting that the type of substrate accumulated and/or enzyme deficient in the lysosome may have a particular effect on the normal cellular composition of the immune system.