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Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis
K C O'Connor1, C Lopez-Amaya, D Gagne
1Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Abstract:
Anti-myelin basic protein (MBP) antibodies in pediatric-onset MS and controls were characterized. Serum samples were obtained from 94 children with MS and 106 controls. Paired CSF and serum were obtained from 25 children with MS at time of their initial episode of acute demyelinating syndrome (ADS). Complementary assays were applied across samples to evaluate the presence, and the physical binding properties, of anti-MBP antibodies. While the prevalence and titers of serum anti-MBP antibodies against both immature and mature forms of MBP were similar in children with MS and in controls, binding characteristics and formal Surface Plasmon Resonance (SPR) studies indicated surprisingly high binding affinities of all pediatric anti-MBP antibodies. Serum levels of anti-MBP antibodies correlated significantly with their CSF levels, and their presence in children with MS was associated with significantly increased risk of an acute disseminated encephalomyelitis-like initial clinical presentation. While antibodies to both immature and mature forms of MBP can be present as part of the normal pediatric humoral repertoire, these anti-myelin antibodies are of surprisingly high affinity, can access the CNS during inflammation, and have the capacity to modulate disease expression. Our findings identify an immune mechanism that could contribute to the observed heterogeneity in spectrum of clinical presentations in early-onset MS.
Insights
In children with multiple sclerosis (MS), anti-myelin basic protein (MBP) antibodies show high affinity. These antibodies in cerebrospinal fluid (CSF) are linked to a more severe initial presentation of MS.
Area of Science:
- Neuroimmunology
- Pediatric Neurology
- Autoimmunity
Background:
- Pediatric-onset multiple sclerosis (MS) presents with diverse clinical manifestations.
- The role of anti-myelin basic protein (MBP) antibodies in the pathogenesis and clinical heterogeneity of early-onset MS remains incompletely understood.
Purpose of the Study:
- To characterize the prevalence, binding properties, and clinical relevance of anti-MBP antibodies in children with MS.
- To investigate the relationship between serum and cerebrospinal fluid (CSF) anti-MBP antibody levels and initial clinical presentation in pediatric MS.
Main Methods:
- Serum samples from 94 children with MS and 106 controls were analyzed.
- Paired serum and CSF samples from 25 children with MS during acute demyelinating syndrome (ADS) were studied.
- Complementary assays, including Surface Plasmon Resonance (SPR), were used to assess anti-MBP antibody binding affinities.
Main Results:
- Prevalence and titers of serum anti-MBP antibodies were similar in pediatric MS and controls.
- All pediatric anti-MBP antibodies exhibited high binding affinities to both immature and mature MBP forms.
- Serum anti-MBP antibody levels correlated with CSF levels and were associated with an increased risk of acute disseminated encephalomyelitis (ADEM)-like presentations.
Conclusions:
- Anti-MBP antibodies in pediatric MS are characterized by high affinity and can access the central nervous system (CNS).
- These antibodies may modulate disease expression and contribute to the heterogeneous clinical spectrum of early-onset MS.
- High-affinity anti-myelin antibodies represent a potential immune mechanism influencing pediatric MS presentation.
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