A humoral response to oligodendrocyte-specific protein in MS - A potentialmolecular mimic

Objective: To determine the antibody response to oligodendrocyte-specific p rotein (OSP) in patients with MS. Background: OSP is a recently identified CNS-specific myelin protein that is abundant and therefore a candidate auto antigen in MS. Methods: The presence of anti-OSP antibodies was determined using Western blot analysis, peptide blots, and ELISA in patients with MS a nd 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 contr ol subjects. Peptide mapping determined that the antibody response was dire cted to a seven aa peptide (OSP 114-120), which has 71% homology with sever al common pathogenic proteins. Using OSP 114-120 as antigen, ELISAs were pe rformed on CSF from 85 MS and 51 control patients. Eighty percent of the sa mples from RRMS patients followed at the University of California at Los An geles 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 foun d 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 thos e using OSP peptides. Conclusions: There is a specific humoral response dir ected against a region of OSP in RRMS patients that cross-reacts with sever al common viral peptides. This suggests a possible role for molecular mimic ry in the development of MS.