Expansion of antibody reactivity in the cerebrospinal fluid of multiple sclerosis patients – follow-up and clinical implications

Here we present a follow-up study of 70 patients with multiple sclerosis over 1 to 106 months. Serum and cerebrospinal fluid sample pairs were obtained from 1 to 5 consecutive lumbar punctures. CSF cell count, the IgG index, local IgG synthesis, oligoclonal bands and the antibody index for measles, rubella or varicella zoster were calculated. Results were analysed with regard to clinical characteristics of the patients.Once an intrathecal antibody response was established, it persisted. De novo antibody response against measles virus developed in 7% of the patients between the first and the second spinal tap. In two of seven patients where 5 consecutive CSF samples were available, the intrathecal antibody response expanded from one to three antigens. Furthermore, an intrathecal measles antibody production was associated with a rapid progression of the disease.These data stress the importance of activated B cells for the disease process and the clinical outcome in multiple sclerosis.An elevated immunoglobulin G (IgG) index and the presence of oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) are a hallmark of multiple sclerosis (MS) [1,2]. Although this finding is not specific for MS, 72 % percent of patients present with an elevated IgG index and even 98 % show an oligoclonal distribution of IgG bands exclusively in the CSF [3,4]. Intrathecal IgG is thought to be the product of B lymphocytes residing in the brain of MS patients after they have crossed the blood brain barrier in an activated state with the help of various co-stimulatory signals [5]. Instead of undergoing apoptosis, the B cells expand clonally within the central nervous system (CNS) giving rise to a persistent antibody production [6]. Despite intense investigations, no single antigen against which the antibodies might be directed has been isolated so far. In contrast, the intrathecal antibody response covers a large number of CNS and non-CNS antigens as well as various pathogens [7-14], includi