Markedly upregulated serum semaphorin 4A as a novel activity marker of myasthenia gravis

Abstract Myasthenia gravis (MG) is an autoantibody‐mediated disease of the neuromuscular junction. Semaphorin 4A (Sema4A) is involved in the activation of T cells in various inflammatory disorders. In this study, we aimed to investigate whether Sema4A is involved in the pathogenesis of MG. We measured serum Sema4A concentrations in 30 treatment‐naïve MG patients with acetylcholine receptor (AChR) antibodies, 7 with muscle‐specific tyrosine kinase (MuSK) antibodies and 21 normal controls. As a result, serum Sema4A levels were significantly higher in patients with AChR antibody‐positive MG and MuSK antibody‐positive MG than in controls ( p ≤ 0.0001 for both MG groups). Serum Sema4A levels were correlated with AChR antibody levels (Spearman's ρ = 0.39, p = 0.03) and MG Foundation of America clinical classification classes (Spearman's ρ = 0.38, p = 0.04) in patients with AChR antibody‐positive MG. In conclusion, high serum Sema4A levels may reflect T‐cell activation, and this molecule could be a potential marker of disease activity in MG.