Cross-reactive idiotypy in cerebrospinal fluid immunoglobulins in multiple sclerosis

Abstract

The presence of oligoclonal bands in cerebrospinal fluid (CSF) in multiple sclerosis (MS) indicates a restricted heterogeneity of immunoglobulin (Ig). The portion of myelin basic protein encompassing residues 80-96 contains epitopes frequently recognized by T and B cells of MS patients. To define further this restricted heterogeneity and to direct further efforts to identify an antigenic target of CSF oligoclonal bands, the presence of idiotope (Id)-bearing antibodies sharing an Id with a murine monoclonal antibody to myelin basic protein peptide 80-89 was examined in the CSF of MS patients. CSF samples from 57 patients with clinically definite MS and 45 patients with other neurological diseases were standardized for amount of IgG and analyzed by immunoblotting for detection of Id-bearing antibodies. Id-bearing Ig was detected in the CSF of 79% of MS patients and 16% of other neurological disease patients. Further statistical analysis revealed an 84% specificity, an 86% positive predictive value, and a 76% negative predictive value of the test. The probability that a positive screening result indicated MS was 81%. Thus, antibodies containing a cross-reactive Id are present preferentially in the CSF of patients with MS compared with those with other neurological diseases. An immune network that has limited V region gene usage likely exists in the CSF and central nervous system of patients with MS and may provide evidence about antigens relevant to the pathogenesis of MS.