A humoral response to oligodendrocyte-specific protein in MS: a potential molecular mimic.
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.
Department of Neurology and the Brain Research Institute, UCLA School of Medicine, Los Angeles, CA 90024, USA. jbronste@ucla.edu
J M
JM
Bronstein
R L
RL
Lallone
R S
RS
Seitz
G W
GW
Ellison
L W
LW
Myers
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000917:Antibody Formation; D001323:Autoantibodies / Q000134:cerebrospinal fluid*; D001402:B-Lymphocytes / Q000276:immunology*; D001921:Brain / Q000473:pathology; D057167:Claudins; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010449:Peptide Mapping; D011994:Recombinant Proteins / Q000276:immunology; D012016:Reference Values; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D001323:Autoantibodies; C120453:CLDN11 protein, human; D057167:Claudins; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins