ISOLATION AND CHARACTERIZATION OF AN OLIGODENDROCYTE PRECURSOR-DERIVED B-CELL EPITOPE IN MULTIPLE-SCLEROSIS

In a search for possible central nervous system-specific autoantigens in multiple sclerosis (MS), a X-phage protein expression library was c onstructed from an oligodendrocyte-precursor cell line. The library wa s screened with pooled cerebrospinal fluid (CSF) from 54 patients with definite MS according to the criteria of Poser. Pooled CSF samples fr om 44 patients with other neurological diseases including bacterial me ningitis and viral encephalitis were used as control. A total of 1,000 ,000 colonies were screened and 6 positive clones were detected. At th e DNA level none of the sequences showed significant homology to a kno wn coding sequence. All 6 clones contained an open reading frame for s mall peptides ranging from 14 to 38 amino acids. It was noteworthy tha t 5 clones contained a common sequence of 7 amino acids, which was hig hly homologous to a translated consensus Alu repeat epitope. Screening of sera and CSF from patients with MS showed that approximately 44% r eacted with these so-called Alu peptides, end-point antibody titers in their sera ranging from 1:1,000 to 1:25,000. In addition, some sample s selected by their reactivity with Ab peptides stained intensively th e cytoplasm of oligodendrocyte precursors but not of astrocytes ex viv o. We postulate that autoantibodies to a hitherto unknown oligodendroc yte precursor-derived B-cell epitope could contribute to the pathogene sis in a subgroup of MS patients.