Altered monocyte expression and expansion of non-classical monocyte subset in XXXX @entity1 .

@entity1 @entity8 @entity56943 @entity5750 @entity310 @entity10736 @entity1503 @entity6994 @entity4071 @entity9589 @entity2383
BACKGROUND: The main defect of immunoglobulin A @entity8 ( @entity6994 ) lies within the immune system and in peripheral blood mononuclear cells rather than in the kidney. Previously, we found an altered gene expression in monocytes compared with B and T cells isolated from @entity6994 @entity1 ; thus, our aim here has been to study this subset at a genome-wide and functional level. METHODS: A total of 39 @entity6994 @entity1 and 37 @entity1503 ( @entity1503 ) were included in this study, and microarray technology was used to evaluate global gene expression differences in monocytes isolated from @entity6994 @entity1 and @entity1503 . Aberrantly expressed genes and pathways were then validated on an independent set of @entity6994 @entity1 with RT-PCR western blot and flow cytometric analysis. RESULTS: Gene expression differences in monocytes from @entity6994 @entity1 and @entity1503 primarily involved apoptosis signalling, @entity2383 , @entity9589 signalling. Both the extrinsic and intrinsic apoptotic pathways seem to be implicated; in particular, the protein levels of @entity56943 and @entity10736 were upregulated thus confirming the altered mitochondrial and death receptor homeostasis. Furthermore, the basal intracellular protein levels of @entity310 in monocytes were lower in @entity6994 @entity1 compared with @entity1503 . We validated at protein level an enhanced apoptotic phenotype and a different subset distribution in monocytes from @entity6994 @entity1 . We found that the non-classical monocyte subset ( @entity5750 (+) @entity4071 (+)) was significantly expanded in all @entity6994 @entity1 tested even though the total monocyte count remained unchanged. CONCLUSIONS: Our findings demonstrate, for the first time, an aberrant modulation of the mitochondrial respiratory system in monocytes isolated from @entity6994 @entity1 . Furthermore, the aberrant expansion of the ( @entity5750 (+) @entity4071 (+)) subset could explain the enhanced apoptotic phenotype seen in these cells thus revealing their potential role in the pathogenesis of @entity6994 .
