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Peptide specificity of anti-myelin basic protein antibodies in patients with acute optic neuritis and the HLA system
F Sellebjerg1, J L Frederiksen, T Olsson
1Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.
Abstract:
Multiple sclerosis (MS) may be an autoimmune disease, partially caused by autoreactivity to myelin basic protein (MBP) and other central nervous system proteins. Acute optic neuritis (ON) is a frequent first symptom of MS. The role of the HLA system in anti-MBP antibody production in ON was investigated employing a restriction fragment length polymorphism system for genomic HLA-DQ and -DR typing and an immunospot assay for the detection of individual cells secreting antibodies to three different synthetic MBP peptides. Thirty-two out of 40 patients (80%) with ON had cells in cerebrospinal fluid secreting anti-MBP peptide antibodies while this occurred in 10/19 patients with other neurological diseases (53%; mainly in patients with inflammatory diseases in the central nervous system). This difference was statistically significant (P = 0.03). None of the three examined peptides were immunodominant in any patient group. It was found, however, that presence of HLA DR15, which is associated with MS, may be associated further with predominant production of antibodies to the MBP amino acids 63-88 in patients with ON (P = 0.002, corrected for multiple comparisons).
Insights
Multiple sclerosis patients with optic neuritis show significant anti-myelin basic protein (MBP) antibody production in cerebrospinal fluid. The HLA-DR15 gene variant may link to specific antibody responses in optic neuritis.
Area of Science:
- Neuroimmunology
- Immunogenetics
Background:
- Multiple sclerosis (MS) is a central nervous system autoimmune disease.
- Acute optic neuritis (ON) is a common initial symptom of MS.
- Autoreactivity to myelin basic protein (MBP) is implicated in MS pathogenesis.
Purpose of the Study:
- To investigate the role of the HLA system in anti-MBP antibody production in patients with ON.
- To determine if specific HLA types are associated with antibody responses to MBP peptides in ON.
Main Methods:
- Genomic HLA-DQ and -DR typing using restriction fragment length polymorphism.
- Immunospot assay to detect antibody-secreting cells in cerebrospinal fluid (CSF).
- Detection of antibodies against three synthetic MBP peptides.
Main Results:
- 80% of ON patients had CSF cells secreting anti-MBP peptide antibodies, significantly higher than other neurological disease patients (53%, P=0.03).
- No single MBP peptide was immunodominant across patient groups.
- The MS-associated HLA-DR15 genotype correlated with predominant antibody production to MBP amino acids 63-88 in ON patients (P=0.002).
Conclusions:
- CSF B-cell reactivity to MBP peptides is common in ON.
- HLA-DR15 may influence the specificity of the autoimmune response in ON, potentially contributing to MS development.