Autologous Hematopoietic Transplantation Reduces Brain Inflammatory and Axoglial Damage Biomarkers in Multiple Sclerosis.

چکیده اصلی

BACKGROUND AND OBJECTIVES: Autologous hematopoietic stem cell transplantation (AHSCT) can induce long-lasting immune tolerance and disease quiescence in patients with severe multiple sclerosis (MS), but the underlying mechanisms are not well understood. We hypothesized that AHSCT would induce persistent decreases in inflammatory cytokines, chemokines, and axoglial damage biomarkers in serum and CSF. METHODS: Longitudinal serum and CSF samples were obtained from 24 participants with severe MS undergoing AHSCT in the HALT-MS trial (NCT00288626), with serum collected at 9 time points from pretreatment through month 60 and CSF collected at 3 time points, including pretreatment, month 24, and month 48. Approximately 50 soluble biomarkers were analyzed to determine treatment-induced changes and associations with disease activity, including clinical and MRI parameters. RESULTS: AHSCT resulted in decreased expression of many proinflammatory cytokines, chemokines, and neuroinflammatory markers for several years in both serum and CSF, including neurofilament light chain (NfL). CSF levels of glial fibrillary acid protein and IL-7, on the contrary, increased after treatment. Expansion of cytomegalovirus and/or Epstein-Barr virus early after AHSCT resulted in transient increases in inflammatory cytokines in serum, but these changes did not persist. Changes in serum were largely distinct from changes in CSF, and concentrations of cytokines and chemokines in serum rarely correlated with concentrations in CSF, except for NfL. DISCUSSION: These results confirm the hypothesis that AHSCT results in long-lasting reductions in inflammatory cytokines, chemokines, and axoglial damage markers, consistent with persistent disease quiescence. The lack of relationships between biomarkers in serum and CSF suggests that these samples largely reflect distinct immunologic processes and compartments, and that analysis of CSF may be warranted for deeper understanding of disease processes in the CNS despite the challenges associated with performing lumbar punctures. Expression of IL-7 in CSF may be an underappreciated biomarker of the inflammatory state in the CNS and warrants further study.

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