Cerebrospinal fluid oligoclonal immunoglobulin gamma bands and long-term disability progression in multiple sclerosis: a retrospective cohort study

Virginija Danylaité Karrenbauer,Ali Manouchehrinia,Jan Hillert,Sahl Khalid Bedri

doi:10.1038/s41598-021-94423-x

Virginija Danylaité Karrenbauer, Ali Manouchehrinia + Show 2 more

Open Access

https://doi.org/10.1038/s41598-021-94423-x

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Abstract

Multiple sclerosis (MS) patients with immunoglobulin gamma (IgG) oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) have different genetic backgrounds and brain MRI features compared to those without. In this study, we aimed to determine whether CSF-OCB status is associated with long-term disability outcomes. We used Swedish MS register data on clinically definite MS patients with known OCB status. Date of birth, age at MS onset, and time to sustained Expanded Disability Status Scale (EDSS) milestones 3, 4, and 6; time to conversion to secondary progressive (SP) MS, sex, and immunomodulatory treatment (IMTs) duration were collected. Multivariate Cox regression models were used to investigate the association between OCB status and risk of reaching each milestone. The OCB-positive group reached disability milestones at an earlier time and younger age. OCB-positivity significantly increased the risk of reaching EDSS 3.0 (HR = 1.29, 95% CI 1.12 to 1.48, P < 0.001) and 4.0 (HR = 1.38, 95% CI 1.17 to 1.63, P < 0.001). The OCB-positive group had a 20% higher risk of conversion to SPMS. CSF-OCB presence is associated with higher risk of reaching EDSS milestones and conversion to SPMS. Our findings suggest higher disease modifying effect of OCB presence in the early inflammatory stages of MS.

Highlights

Multiple sclerosis (MS) patients with immunoglobulin gamma (IgG) oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) have different genetic backgrounds and brain MRI features compared to those without
Age at MS onset was 1.9 years earlier in OCB-positive group compared with OCB-negative (standardized mean difference (SMD): 0.17, p < 0.001)
In the OCB-negative group, platform immunomodulatory treatments (IMTs) were started on average at a 2.5 years older age in the OCBnegative group compared with OCB-positive (SMD: 0.24, p < 0.001)

Summary

Introduction

Multiple sclerosis (MS) patients with immunoglobulin gamma (IgG) oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) have different genetic backgrounds and brain MRI features compared to those without. We aimed to determine whether CSF-OCB status is associated with longterm disability outcomes. The OCB-positive group had a 20% higher risk of conversion to SPMS. CSF-OCB presence is associated with higher risk of reaching EDSS milestones and conversion to SPMS. Abbreviations CI Confidence interval CIS Clinically isolated syndrome CNS Central nervous system CSF Cerebrospinal fluid EDSS Expanded disability status scale HLA Human leukocyte antigen HR Hazard ratio IgG Immunoglobulin G IgM Immunoglobulin M IMT Immunomodulatory treatment MS Multiple sclerosis OCB Oligoclonal bands PP Primary progressive RR Relapsing remitting SD Standard deviation SP Secondary progressive SPMS Secondary progressive multiple sclerosis. Given the paucity of evidence, we conducted a registry based study to investigate whether OCB confers higher risk of long-term disability worsening in MS

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