The role of @entity1356 in the pathophysiology of XXXX .

@entity1 @entity32 @entity650 @entity14818 @entity11773 @entity558 @entity1910 @entity1356 @entity26165 @entity6800 @entity2939 @entity4841 @entity8649
INTRODUCTION: @entity14818 ( @entity14818 ) is a disabling @entity8649 , characterized by a chronic @entity1910 , an M-protein, @entity4841 , and other signs of systemic @entity32 . @entity1356 ( @entity1356 antibodies are highly effective, but the pathophysiology is still largely unknown. Here we studied the effect of in-vivo @entity1356 inhibition on serum markers of @entity32 and cellular immune responses. METHODS: Eight @entity1 with @entity14818 received monthly subcutaneous (s.c.) injections with 150 mg canakinumab for six months. Blood was drawn for measurement of serum markers of @entity32 (12 times per @entity1 ) and for functional and phenotypic analysis of both freshly isolated and toll-like receptor (TLR)-ligand-stimulated peripheral blood mononuclear cells (PBMCs) (five times per @entity1 ). All data were compared to results of healthy controls. RESULTS: @entity650 levels in serum and in lysates of freshly isolated PBMCs and serum myeloid-related protein ( @entity11773 )/14 and S100A12 levels correlated with disease activity. In vitro, @entity558 stimulation resulted in higher @entity650 and @entity1356 production in PBMCs from symptomatic @entity14818 @entity1 compared to healthy controls, whereas @entity1 cells were relatively hyporesponsive to poly:IC and Pam3Cys. The mRNA microarray of PBMCs showed distinct transcriptomes for controls, symptomatic patients and anti- @entity1356 -treated @entity1 . Numbers of T- and B-cell subsets as well as M-protein concentrations were not affected by @entity1356 inhibition. Free light chain levels were elevated in 4 out of 8 @entity1 . CONCLUSIONS: In conclusion, @entity1 PBMCs are hyperresponsive to @entity558 , and clinical efficacy of @entity1356 inhibition in @entity1 with @entity14818 is associated with in-vivo and ex-vivo suppression of @entity32 . Interestingly, @entity1 PBMCs showed divergent responses to @entity26165 , @entity6800 and @entity2939 ligands. Our data underscore that @entity1356 plays a pivotal role in @entity14818 .
