TGF-beta signaling is altered in the peripheral blood of subjects with multiple sclerosis

Multiple sclerosis (MS) is a central nervous system inflammatory disorder with evidence of peripheral immune dysregulation. Abnormalities of the immune suppressive cytokine TGF-beta have been reported, but not fully defined, in MS. Through a pathway-focused expression profiling of the peripheral blood, we found abnormalities of TGF-beta RII, SMAD4 and SMAD7 expression in subjects with MS, and reduction in the levels of TGF-beta regulated genes, indicating an overall reduction in TGF-beta signaling in MS. The response to exogenous TGF-beta was intact, however, indicating an extrinsic defect of TGF-beta signaling in MS. These results indicate that TGF-beta control is diminished in MS. Published by Elsevier B.V.