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. In MPS VI, there is dermatan sulfate lysosomal accumulation due to pathogenic mutations in the ARSB gene, leading to arylsulfatase B deficiency. Alterations in the immune system of MPS mouse models have already been described, but data concerning MPSs patients is still scarce. 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 discovered 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 memory T cell frequency 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 deficiency in the lysosome may have a particular effect on the normal cellular composition of the immune system.

Buffy Coat Processing Impacts on Monocytes' Capacity to Present Lipid Antigens.

Buffy Coats, generated from a blood donor's whole blood bag unit, are commonly used in biomedical research as a source of leukocytes due to the high number of cells that can be recovered from each Buffy Coat. Buffy Coats are leukocyte-enriched residual units obtained by centrifugation of whole blood. At the blood bank, blood can be processed using two different protocols according to the time interval between blood collection and processing. When blood collection and processing occur on the same day, it gives rise to Fresh Blood Buffy Coats. Alternatively, if blood processing only happens on the day after blood collection, Overnight Blood Buffy Coats are created. In this study, we aimed to address whether these two different Buffy Coat-processing protocols could differently impact monocyte function as antigen-presenting cells. For this purpose, we analyzed in the same experiment monocytes isolated from Fresh Blood and from Overnight Blood Buffy Coats. We assessed lipid antigen presentation by CD1d to invariant Natural Killer T (iNKT) cells. CD1d is a non-polymorphic MHC class I-like protein, which facilitates the study of antigen presentation among allogeneic samples. The results show that monocytes from Fresh Blood Buffy Coats have a better capacity to present antigens by CD1d, and consequently to activate iNKT cells, when compared to monocytes from Overnight Blood Buffy Coats. The differences observed were not explained by disparities in monocyte viability, CD1d expression, or basal activation state (monocyte expression of CD40 and CD80). Buffy Coats are a valid source of blood cells available daily. Hence, the type of protocol for Buffy Coat processing should be carefully considered in day-to-day research, since it may lead to different outcomes.

The Biology of Lysosomes: From Order to Disorder.

Since its discovery in 1955, the understanding of the lysosome has continuously increased. Once considered a mere waste removal system, the lysosome is now recognised as a highly crucial cellular component for signalling and energy metabolism. This notable evolution raises the need for a summarized review of the lysosome's biology. As such, throughout this article, we will be compiling the current knowledge regarding the lysosome's biogenesis and functions. The comprehension of this organelle's inner mechanisms is crucial to perceive how its impairment can give rise to lysosomal disease (LD). In this review, we highlight some examples of LD fine-tuned mechanisms that are already established, as well as others, which are still under investigation. Even though the understanding of the lysosome and its pathologies has expanded through the years, some of its intrinsic molecular aspects remain unknown. In order to illustrate the complexity of the lysosomal diseases we provide a few examples that have challenged the established single gene-single genetic disorder model. As such, we believe there is a strong need for further investigation of the exact abnormalities in the pathological pathways in lysosomal disease.