Multiple sclerosis: possible biomarkers for early progression of disability identified
Prominent antibodies in cerebrospinal fluid
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.
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.
Christiane Gasperi, Anke Salmen, Gisela Antony, Antonios Bayas, Christoph Heesen, Tania Kümpfel, Ralf A. Linker, Friedemann Paul, Martin Stangel, Björn Tackenberg, Florian Then Bergh, Clemens Warnke, Frank Weber, Heinz Wiendl, Brigitte Wildemann, Uwe K. Zettl, Ulf Ziemann, Frauke Zipp, Hayrettin Tumani, Ralf Gold, Bernhard Hemmer: Association of Intrathecal Immunoglobulin G Synthesis With Disability Worsening in Multiple Sclerosis, Jama Neurology, April 29, 2019, DOI: 10.1001/jamaneurol.2019.0905