Using B Cell Characteristics as Predictors of Multiple Sclerosis in Clinically Isolated Syndrome Patients
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Clinically isolated syndrome (CIS) is the diagnosis of patients who have experienced a single event due to nerve demyelination of the white matter of the central nervous system. This can be due to numerous causes, both autoimmune and infectious. We hypothesized that CIS patients with B cell characteristics like those seen in multiple sclerosis (MS) patients would develop clinically definite MS. We have determined that, like MS patients, several CIS patients have an increased frequency of VH4-expressing CD19\super +\nosupersub B cells in their cerebrospinal fluid (CSF) compared to peripheral B cells from healthy donors (HCPB) or CSF B cells from patients with neurological diseases not related to MS. However, VH4 bias was a moderate predictor for conversion to MS. Nevertheless, detailed analysis of antibody V-gene repertoires revealed eight codons that are significantly more mutated in the MS CSF than HCPB VH4-expressing B cells. This MS-specific antibody signature includes 25% of all mutations within the repertoires of CSF-derived B cells from MS patients. We then used the prevalence of this signature to predict if CIS patients converted to MS within two years of repertoire sampling. Indeed, we accurately predicted conversion to MS in 10 of 11 CIS patients. The B cell VH4 antibody signature can potentially be used as a diagnostic and prognostic tool for MS.