Evolving Identification of Blood Cells Associated with Clinically Isolated Syndrome: Importance of Time since Clinical Presentation and Diagnostic MRI.

Stephanie Trend,David Nolan,Marzena Fabis-Pedrini,Anderson Jones,Robyn Lucas,Sian Geldenhuys,David Booth,Prue Hart,Scott Byrne,Allan Kermode,William Carroll

doi:10.3390/ijms18061277

Abstract

It is not clear how the profile of immune cells in peripheral blood differs between patients with clinically isolated syndrome (CIS) and healthy controls (HC). This study aimed to identify a CIS peripheral blood signature that may provide clues for potential immunomodulatory approaches early in disease. Peripheral blood mononuclear cells (PBMCs) were collected from 18 people with CIS, 19 HC and 13 individuals with other demyelinating conditions (ODC) including multiple sclerosis (MS). Individuals with CIS separated into two groups, namely those with early (≤14 days post-diagnostic magnetic resonance imaging (MRI); n = 6) and late (≥27 days; n = 12) blood sampling. Transitional B cells were increased in the blood of CIS patients independently of when blood was taken. However, there were two time-dependent effects found in the late CIS group relative to HC, including decreased CD56bright NK cells, which correlated significantly with time since MRI, and increased CD141+ myeloid dendritic cell (mDC2) frequencies. Higher CD1c+ B cells and lower non-classical monocyte frequencies were characteristic of more recent demyelinating disease activity (ODC and early CIS). Analysing cell populations by time since symptoms (subjective) and diagnostic MRI (objective) may contribute to understanding CIS.

Highlights

Isolated syndrome (CIS) is often the first indication of multiple sclerosis (MS), though prediction of disease course in individuals with Clinically isolated syndrome (CIS) is challenging, with few markers to predict conversion to MS [1]
To investigate whether we could find a CIS-specific signature, we initially compared the frequency of peripheral blood mononuclear cell (PBMC) subsets in all people with CIS to those with other demyelinating conditions (ODC) and healthy controls (HC) (Table A1)
Unless the similarity between HC and CIS is an effect of the small sample size of our early CIS group, these findings suggest that CIS is immunologically distinct from ODC in their capacity for immune cells to stabilise to “normal” levels after a demyelinating event in the central nervous system (CNS)

Summary

Introduction

Isolated syndrome (CIS) is often the first indication of multiple sclerosis (MS), though prediction of disease course in individuals with CIS is challenging, with few markers to predict conversion to MS [1]. Blood samples taken from people with other acute demyelinating conditions (and recent clinically-evident disease) were included to provide evidence as to whether changes observed were generally associated with MRI demyelination or were specific to CIS at high risk of conversion to MS. We found that when time since MRI diagnosis and clinical presentation was accounted for in the CIS group, changes to cell subset frequencies in sampled blood emerged that differentiated those with recent diagnosis from those with a delay since diagnosis.

Study Participant Demographics

B Transitional B cells

Study Participants

Flow Cytometry

Statistical Analyses