Prominent Antibodies in Cerebrospinal Fluid

Multiple sclerosis: possible biomarkers for early progression of disability identified

cerebrospinal fluid
Prof. Bernhard Hemmer, talking with his staff members. Image: M. Jooss / TUM

The progression of multiple sclerosis (MS) can vary markedly from one patient to the next, yet until now there has been no reliable way to predict whether and, if so, to what extent disability is likely to develop. In a research project of the Disease-Related Multiple Sclerosis Competence Network (KKNMS), a working group at the Technical University of Munich (TUM) has recently shown that elevated levels of specific antibodies in the nervous system are telltale signs of early and rapidly progressing disability.

To diagnose multiple sclerosis, doctors sample cerebrospinal fluid (CSF) by a procedure known as a spinal tap or lumbar puncture. The research team, headed by Professor Bernhard Hemmer, director of the Neurology Department at the TUM’s Klinikum rechts der Isar and chair of the KKNMS, examined CSF samples from 637 MS patients who were observed regularly over a period of four years to monitor their disability status.

Data for the study were drawn from the National MS Patient Cohort of the KKNMS, which includes 1,376 patients enrolled at 18 study sites since 2010. The patients’ data and biological samples were collected at baseline, one year later and every two years thereafter.

Elevated IgG values as possible biomarkers

The group was able to show that elevated levels of a specific antibody in the nervous system, immunoglobulin G (IgG), are associated with an increased risk of disability, irrespective of the occurrence of relapses or treatment with disease-modifying drugs. Progression also occurred earlier in patients with elevated CSF levels of antibodies than in patients with normal antibody levels.

Elevated antibody concentrations in the CSF indicate that those antibodies are being produced in the central nervous system, a process known as intrathecal IgG synthesis. Four years after baseline, 28.4% of patients with intrathecal IgG synthesis but only 18.1% of patients without IgG synthesis experienced a fall in their EDSS score, which measures disability status.

“Our data show that a routine lab test of cerebrospinal fluid is also useful for assessing the long-term course of multiple sclerosis. Knowledge of such parameters can help us assess the prognosis of patients more reliably and provides a better basis for sound therapeutic decisions,” says Professor Bernhard Hemmer, MD, summarizing the study findings. Links between other routine CSF parameters and deterioration of the disability status were investigated, but no such correlations were found.