Biomarkers of Intrathecal Inflammation in Multiple Sclerosis and Other Disorders

By Jai Perumal, MD

Assistant Professor of Neurology, Weill Cornell Medical College

SYNOPSIS: A study aimed at addressing intrathecal immune biomarkers in neuro-immunological diseases finds that the spike of activated T and B cells in both progressive and relapsing MS originated differently, with the former’s increase primarily traced to immune cells in brain tissue.

SOURCE: Kimori M, et al. Cerebrospinal fluid markers reveal intrathecal inflammation in progressive multiple sclerosis. Ann Neurol 2015;78:3-20.

Modern management of multiple sclerosis and other neuro-inflammatory diseases necessitates more thorough evaluation of intrathecal inflammation in clinical practice than the MR imaging of contrast enhancing lesions and case-specific oligoclonal bands in cerebrospinal fluid that are currently utilized, as these biomarkers are unspecific and devoid of any information into the processes spurring the inflammation. Oligoclonal bands and Elevated IgG index have a static nature that cannot aid in monitoring a patient’s evolving response to treatment and therapy. Biomarkers that could succeed where the above two cannot, as well as in-depth understanding of the immune mechanisms that precede diseases like progressive multiple sclerosis, inevitably provide more effective treatment strategies and more optimal results. Furthermore, these would ideally act as evaluative measures for various clinical trials, particularly in shorter-term therapy studies. Seeking to bridge the gap between current evidence and optimal patient care, Kimori et al analyzed alternative spinal fluid biomarkers to formulate a series of biomarker profiles that would effectively identify and diagnose various diseases as well as allow more complete monitoring of the progression of disease state.

In a 6-year independent cohorts trial composed of 386 patients—not only patients with MS, but patients with various inflammatory and non-inflammatory neurological diseases—Kimori et al analyzed an assortment of CSF biomarkers in both groups, relying on both more standard CSF tests and less routine tests like an electrochemiluminescent assay. Immune cell assays were also taken, as the CSF immune cells were the sources of the drawn biomarkers. In the analysis of results comparing test cohorts with controls, the inflammatory neurological disorders group and the MS patients saw CD27 levels that consistently and drastically differed from non-inflammatory neurological disease patients and healthy controls. Further calculations regarding certain biomarkers were conducted, the conclusion of which suggested that higher ratios of the biomarker CD27’s levels were sourced to secretions from embedded CNS immune cells. In further comparisons, patients with progressive multiple sclerosis had CD27 levels that significantly differentiated themselves from controls, other inflammatory neurological diseases and even from relapse-remitting multiple sclerosis, indicating that the inflammation of progressive MS is sourced to CNS tissue immune cells as opposed to systemic circulation of cerebrospinal fluid, as is the case with relapsing-remitting MS. The study’s model was unable to determine an individual biomarker that could identify specific disorders sufficiently (>60% accuracy); however, of the biomarkers tested, sCD27/T cell ratios proved to be the most predictive of intrathecal inflammation.