Dendritic cells in patients with type I Gaucher disease are decreased in number but functionally normal

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

“…The estimated life expectancy for splenectomized GD is lower than that for nonsplenectomized patients, and the causes of death linked to splenectomy were malignancies, cardiovascular disease, and cerebrovascular disease (104,105,114,118,177,181). In a retrospective study, the incidence of malignancies in a cohort of patients with GD1 showed no statistically significant difference relative to agematched subjects.…”

“…Both myeloid and plasmacytoid DC and the yield of the monocyte-derived DC were obtained due to a decrease in GM-CSF and IL-4 stimulation. CD34ϩ cell differentiation in the presence of GM-CSF, SCF, TNF-␣, and IL-4 into mature DCs was normal (95,118,122).…”

“…Patients with GD exhibit quantitative defects in their DCs as demonstrated by decreased circulating DC precursors in both myeloid and plasmacytoid types (95,118,122). Numbers of myeloid (mDC) and plasmacytoid (pDC) DCs were decreased.…”

“…However, cases of type I GD coexisting with relatively low serum immunoglobulins, impaired antibody production, and recurrent bacterial infections have been described (82,83,87). All of these underscore that ineffective T cell control exposes GD patients to inflammatory reactions, poor immune responses against infectious agents, and impaired immune surveillance associated with an increased risk of neoplasm (93,95,118,122,161,165). A contrasting point of view suggests that GC accumulation may result to several evolutionary advantages (79,88,83), as secondary biochemical pathways upstream and downstream of GC that regulate phospholipid metabolism are affected in GD.…”

Severe Impairment of Regulatory T-Cells and Th1-Lymphocyte Polarization in Patients with Gaucher Disease

“…Clinical and experimental studies have shown that GD patients exhibit various immunological abnormalities, such as increased susceptibility to infections (Aker et al 1993;Maródi et al 1995), numerical dendritic cell defects (Micheva et al 2006), and an increased incidence of B-lymphoproliferative disorders and solid tumors (Arends et al 2013). Laboratory findings include elevated levels of acute-phase proteins (Rogowski et al 2005) and serum immunoglobulin levels (de Fost et al 2008), frequent occurrence of monoclonal gammopathy (Arends et al 2013), detection of various autoantibodies in patients' serum (Shoenfeld et al 1995), and increased plasma levels of proinflammatory cytokines, including IL-1b, IL-6, IL-8, IL-10, TNF-a, and TGF-b (Allen et al 1997;Barak et al 1999;Michelakakis et al 1996;Deegan et al 2005;Pérez Calvo et al 2000).…”