Analysis oftarget anfigens in oerebrospinal oligoclonal bands in multiple sclerosis patients

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Cerebrospinal fluid (CSF) oligoclonal lgG band (OS) is an important laboratory finding in multiple sclerosis (MS). Since its clinical implication and target antigens remain to be elucidated, we conducted the following analyses. We applied the sensitive isoelectric focusing (IEF) method to detect OB in MS and found that the frequencies of OB were 67.9% in conventional MS (CMS) and 10% in optic-spinal MS (OSMS). Interestingly, the brain MRI findings in OB-negative CMS patients were often atypical. We studied the CSF lgG epitopes with the phage display method. Common aminoacid sequences were detected in each case, and they were frequently homogenous to herpes viral proteins. However, those sequences in each patient were unique. We analyzed the 3 CSF samples of an OB-positive patient and consistently detected the identical sequences homologous to EB viral proteins. Among them, the sequence homologous to EB viral ZEBRA protein reacted more to CSF than serum in VVestern blot, suggesting the relevance to OB. The GST fusion proteins were synthesized, and the CSF lgG reacted to the fusion protein were precipitated in the GST pull down assay. After the absorption, the CSF was subjected to IEF, but the banding pattern of OB was unchanged. Therefore, each band of OB probably consists of multiple antibodies. The viral IL-1O was not detected in any CSF sample obtained during relapse. Some patients have linear trigeminal root lesions, and these unique lesions are similar to those caused by herpes simplex viral infection in animals. The CSF antibody titers to herpes virus were elevated in one OB-positive patient with such lesion during relapse. Our study demonstrated the pathogenetic significance of OB in MS. The peptide sequences shown to react to CSF lgG in MS in the present study may be an important information to further analyze the target antigens of OB.