Tu119 - Effect of AHSCT on Inflammatory Mediators in Serum and CSF of RRMS Patients in the HALT-MS Study

Pradeepthi Bathala – Meso Scale Diagonostics, LLC; Jacob Wohlstadter – Meso Scale Diagonostics, LLC; Maria Teresa Cencioni – Imperial College London; Jose Fernandez Velasco – Hospital Universitario Ramón y Cajal; David Fox – University of Michigan; Linda Griffith – NIAID, NIH; Kristina Harris – Immune Tolerance Network; Noha Lim – Immune Tolerance Network; Paolo Muraro – Imperial College London; Richard Nash – Colorado Blood Cancer Institute; Martin Stengelin – Meso Scale Diagonostics, LLC; Luisa Villar – Hospital Universitario Ramón y Cajal

Abstract Text: Autologous hematopoietic stem cell transplantation (AHSCT) is a treatment option for highly active multiple sclerosis (MS). In the HALT-MS study, twenty-four participants underwent AHSCT, of which seventeen achieved durable remission. Remission following AHSCT is thought to be mediated by shifts in the reconstituted immune system favoring immunoregulation over inflammation, which we hypothesized would be reflected in cytokine and chemokine expression. We analyzed soluble markers in serum and cerebrospinal fluid (CSF) from HALT-MS participants before and after AHSCT. Objectives included determining effects of AHSCT, associations with clinical parameters, relationships between serum and CSF, and prognostic value of baseline data.

CSF levels of IgG, IgM, NfL, and GFAP, biomarkers of MS activity, were significantly altered by AHSCT at 24 months, consistent with reduced disease activity. In serum, AHSCT resulted in persistent changes in NfL but not GFAP. Serum NfL, CSF NfL, and CSF GFAP correlated with clinical activity, including EDSS and MRI measures.

Consistent with declining neuroinflammation, AHSCT decreased intrathecal levels of inflammatory cytokines and chemokines at 24 months, including IL-12/23p40, IFN-gamma, IL-6, IL-10, CCL19, CCL22, and ICAM1. In serum, AHSCT resulted in many acute changes consistent with immune ablation and reconstitution, but few persistent effects. Only two serum cytokines were significantly decreased at 24 months: TNF-alpha and MIP1-beta. Using repeated measure modeling of serum biomarkers across all timepoints, the strongest associations with disease activity were TNF-alpha and MIP1-beta.

These results demonstrate that AHSCT-induced immune reconstitution reduced serum and CSF levels of cytokines and neuroinflammatory markers, which correlated with reduced disease activity.