UNASSIGNED: @entity8410 and @entity32969 ( @entity32969 ), which control B cell homeostasis, are therapeutic targets in @entity792 . @entity24603 -Fc (atacicept), a soluble fusion protein containing the extracellular domain of the @entity8410 - @entity32969 receptor @entity24603 , was applied in clinical trials. However, disease activity in @entity15 unexpectedly increased, whereas in @entity1252 , atacicept was beneficial. In this study, we show that an endogenous soluble @entity24603 (sTACI) exists in vivo. @entity24603 proteolysis involved shedding by a disintegrin and metalloproteinase 10 releasing sTACI from activated B cells. The membrane-bound stub was subsequently cleaved by y-secretase reducing ligand-independent signaling of the remaining C-terminal fragment. The shed ectodomain assembled ligand independently in a homotypic way. It functioned as a decoy receptor inhibiting @entity8410 - and @entity32969 -mediated B cell survival and NF-kB activation. We determined sTACI levels in @entity792 with established hyperactivation of the @entity8410 - @entity32969 system. sTACI levels were elevated both in the cerebrospinal fluid of the brain-restricted @entity792 @entity15 correlating with intrathecal IgG production, as well as in the serum of the systemic @entity792 @entity1252 correlating with disease activity. Together, we show that @entity24603 is sequentially processed by a disintegrin and metalloproteinase 10 and y-secretase. The released sTACI is an immunoregulator that shares decoy functions with atacicept. It reflects systemic and compartmentalized B cell accumulation and activation.

The Immunoregulator Soluble XXXX Is Released by ADAM10 and Reflects B Cell Activation in Autoimmunity.

@entity24603 :: ('23495', 'Gene') :: ['TACI'] @entity8410 :: ('10673', 'Gene') :: ['BAFF'] @entity1252 :: ('MESH:D008180', 'Disease') :: ['systemic lupus erythematosus'] @entity32969 :: ('8741', 'Gene') :: ['a proliferation-inducing ligand', 'APRIL'] @entity792 :: ('MESH:D001327', 'Disease') :: ['autoimmune disease', 'autoimmune diseases'] @entity15 :: ('MESH:D009103', 'Disease') :: ['multiple sclerosis']
@entity24603 :: (23495,Gene) :: ['TACI']
