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A humoral response to oligodendrocyte-specific protein in MS: a potential molecular mimic
J M Bronstein1, R L Lallone, R S Seitz
1Department of Neurology and the Brain Research Institute, UCLA School of Medicine, Los Angeles, CA 90024, USA. jbronste@ucla.edu
Objective:
To determine the antibody response to oligodendrocyte-specific protein (OSP) in patients with MS.
Background:
OSP is a recently identified CNS-specific myelin protein that is abundant and therefore a candidate autoantigen in MS.
Methods:
The presence of anti-OSP antibodies was determined using Western blot analysis, peptide blots, and ELISA in patients with MS and in other neurologic and normal control subjects.
Results:
Using Western blot analysis, seven patients with relapsing-remitting MS (RRMS) were found to contain anti-OSP antibodies in their CSF that were not present in control subjects. Peptide mapping determined that the antibody response was directed to a seven aa peptide (OSP 114-120), which has 71% homology with several common pathogenic proteins. Using OSP 114-120 as antigen, ELISAs were performed on CSF from 85 MS and 51 control patients. Eighty percent of the samples from RRMS patients followed at the University of California at Los Angeles had an ELISA reading above 0.55 optical density units, whereas all 20 control CSF samples had values less than 0.55 U. Similar results were found in specimens from an outside research bank. ELISAs performed on CSF using homologous viral peptides as antigen showed a close correlation with anti-OSP 114-120 ELISA readings, and in some, the readings were higher than those using OSP peptides.
Conclusions:
There is a specific humoral response directed against a region of OSP in RRMS patients that cross-reacts with several common viral peptides. This suggests a possible role for molecular mimicry in the development of MS.
Insights
Multiple sclerosis patients show a specific antibody response to oligodendrocyte-specific protein (OSP). This immune reaction, particularly in relapsing-remitting MS, may involve molecular mimicry with viral peptides, suggesting a potential cause for MS.
Area of Science:
- Neuroimmunology
- Autoimmunity in CNS disorders
Background:
- Oligodendrocyte-specific protein (OSP) is a CNS myelin protein and a potential autoantigen in multiple sclerosis (MS).
- Understanding autoimmune targets in MS is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the antibody response against OSP in patients diagnosed with MS.
- To identify specific OSP epitopes targeted by antibodies in MS patients.
Main Methods:
- Western blot analysis and peptide blots were used to detect anti-OSP antibodies in cerebrospinal fluid (CSF).
- Enzyme-linked immunosorbent assays (ELISAs) were employed to quantify antibody levels against OSP peptides in MS and control cohorts.
- Peptide mapping identified the specific OSP region (OSP 114-120) targeted by antibodies.
Main Results:
- Anti-OSP antibodies were detected in the CSF of seven relapsing-remitting MS (RRMS) patients, but not in controls.
- Antibody response was primarily directed against the OSP 114-120 peptide, which shares homology with common pathogenic proteins.
- ELISAs confirmed a significantly higher prevalence of anti-OSP 114-120 antibodies in RRMS patients compared to controls.
- CSF antibody levels against OSP peptides correlated with those against homologous viral peptides.
Conclusions:
- A specific humoral immune response targets a region of OSP in RRMS patients.
- This response exhibits cross-reactivity with common viral peptides, suggesting a role for molecular mimicry in MS pathogenesis.
- Findings indicate OSP may be an autoantigen in MS, potentially triggered by viral infections.