Differences in immune-related semaphorin levels in the CSF and serum of newly diagnosed, treatment-naive patients with relapsing-remitting multiple sclerosis: a case-control study.

Background: The pathogenesis of multiple sclerosis (MS) remains incompletely elucidated. Semaphorins play an active role in the immune and nervous systems by regulating receptor-mediated adhesion mechanisms. Immunosemaphorins have recently emerged as diagnostic biomarkers or therapeutic targets in MS. Objectives: This study aimed to investigate alterations in semaphorins (Sema) 3A, 3F, 4A, 4D, and 7A in newly diagnosed, treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS). Methods: In this prospective case-control study, semaphorin levels were evaluated by enzyme-linked immunosorbent assay in 40 consecutive patients (serum and cerebrospinal fluid (CSF)) and 40 healthy controls (serum). Results: Serum levels of Sema3A, Sema4A, Sema4D, and Sema7A were lower in RRMS patients than in healthy controls and remained significant after correction for multiple testing. In exploratory analyses, OCB count was negatively correlated with serum Sema4A and Sema7A and positively correlated with CSF Sema7A. Patients with an OCB count ≥12 had lower serum levels of Sema3F, Sema4A, and Sema7A. Sema4D levels were higher in patients with an IgG index ≥0.7. Patients with infratentorial lesions had lower serum Sema4A levels and higher CSF Sema4A levels. Conclusion: Low serum levels of Sema3A may be diagnostically relevant in RRMS. Low serum levels of Sema7A and elevated CSF levels may be associated with inflammatory immune activation. Further studies are needed for Sema3F, Sema4A, and Sema4D.