Rinsho Shinkeigaku (Clinical Neurology)

Progress of the Year 2014

Sema4A as a biomarker predicting responsiveness to IFN β treatment

Yuji Nakatsuji, M.D.1)

1)Department of Neurology, Osaka University Graduate School of Medicine

Approximately one-third of patients with multiple sclerosis (MS) exhibit markedly high-level-expression of Sema4A. The expression of Sema4A is increased on DCs in MS patients and shed from these cells in a metalloproteinase-dependent manner. DC-derived Sema4A is critical for Th17 cell differentiation, and MS patients with high Sema4A levels exhibit Th17 skewing. Furthermore, patients with high Sema4A levels have more severe disabilities and are unresponsive to IFN-β treatment. We investigated whether recombinant Sema4A abrogates the efficacy of IFN-β in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Administration of Sema4A concurrently with IFN-β abrogated the efficacy of IFN-β. These effects of Sema4A were attributed to promote Th1 and Th17 differentiation and to increase adhesive activation of T cells to endothelial cells, even in the presence of IFN-β.Thus unresponsiveness to IFN-β treatment of MS patients with high Sema4A was also confirmed by model mice EAE. We recommend assaying Sema4A first, and then selecting DMD other than IFN-β for patients with high Sema4A.
Full Text of this Article in Japanese PDF (331K)

(CLINICA NEUROL, 54: 972|974, 2014)
key words: multiple sclerosis, Sema4A, biomarker, interferon, responder

(Received: 23-May-14)