Cerebrospinal Fluid Immunoglobulins and Viral Antibodies in Multiple Sclerosis

Abstract

AbstractAgarose isoelectric focusing (AIF) of cerebrospinal fluid (CSF) and serum from 998 patients revealed two or more oligoclonal bands in CSF from 95% of patients with multiple sclerosis (MS) and 14% of patients with a variety of neurological disorders, including in 22 of 68 patients with paraesthesia, 19 of 162 with cerebral infarction, 5 of 17 with dementia of unknown cause, 12 of 53 with polyneuropathy and 3 of 4 with systemic lupus erythematosus. AIF is a valuable alternative for the demonstration of oligoclonal bands in routine clinical work, superior to Polyacrylamide IF because of easiness in handling, non-toxicity, and separation also of high molecular size proteins.AIF and subsequent immunofixation with radiolabeled anti-human IgG Fc fragment antiserum carried out on unconcentrated CSF from 287 patients revealed oligoclonal IgG bands in 98% of MS patients and 21% of patients with other neurological disorders. The method is of value especially when only small CSF volumes are available.Polyacrylamide IF followed by immunofixation with viral antigens and autoradiography revealed production within the central nervous system (CNS) of antibodies against at least one of 4 different viruses in 21 of 25 patients with MS, and production within the CNS of antibodies against at least one of 6 different viruses in 8 of 9 patients with acute cerebrovascular disease who were selected because they had oligoclonal bands in CSF. In both MS and cerebrovascular disease, the intrathecally produced viral antibodies detected on the autoradiograms could be traced to oligoclonal and/or polyclonal CSF IgG bands on the corresponding IF plates but the majority of oligoclonal IgG bands remained unidentified regarding antibody specificity, and the viral antibodies demonstrated constituted most probably only a minor portion of the intrathecally produced IgG. They may reflect a non-specific, compartmentalized polyclonal B cell activation that is perhaps induced by lipophilic membrane components which are released as a consequence of demyelination or brain tissue destruction.