Emerging and Established Biomarkers
The chart below displays a partial list of current and potential biomarkers for MS.
The first biomarkers listed are those seen through imaging, using magnetic resonance imaging (MRI), optical coherence tomography (OCT), and visual evoked potential (VEP) testing.
The second biomarkers listed are those found within bodily fluids – also referred to as “humoral” – and often relating to antibodies and immune responses.
These two types of biomarkers represent promising areas of research aimed at diagnosing MS earlier, determining the prognosis of one’s MS more precisely, and pinpointing optimal treatments for each individual with MS.
Imaging Biomarkers
| BIOMARKER | SIGNIFICANCE/ROLE |
| MRI – central vein sign | Small vein running through the center of a brain lesion. Indicates inflammation and demyelination. Supports diagnosis of MS. |
| MRI – gadolinium enhancement | White “enhanced” region on MRI following injection of the contrast agent gadolinium. Indicates an active lesion with inflammatory activity. |
| MRI – location of lesions | Correlates with types of symptoms a person is experiencing or likely will experience. Helps to classify type of MS. Identifying lesions in multiple locations can help fulfill McDonald criteria for “dissemination in space.” |
| MRI – paramagnetic rim lesions | MS lesions encircled by a thin, dark rim of iron-rich cells. Marker of increased risk for disability progression and brain atrophy. |
| Optical coherence tomography | Non-invasive procedure that uses light waves to examine the retina and measure its layers and structures. Can identify optic nerve inflammation and help confirm the diagnosis of MS. |
| Visual evoked potential testing | Non-invasive test that tracks brain waves to assess a person’s visual pathway, which consists of the eye, optic nerve, and brain. Abnormal findings can indicate optic nerve inflammation due to MS or other causes. |
Fluid Biomarkers
| AQP4-IgG | Test for antibodies to aquaporin-4, or AQP4. Can help shift diagnostic focus from MS to neuromyelitis optica spectrum disorders (NMOSD). |
| Cerebrospinal fluid (CSF) IgG Index | Measure of immunoglobulins (disease-fighting glycoproteins also known as antibodies) in the spinal fluid. Elevated levels reflect abnormal immune activity in the CNS. Can help in the diagnosis of MS, although other potential causes must be considered. |
| Chemokine (C-X-Cmotif) ligand13 (CXCL13) |
A protein that acts as a signaling molecule to attract B cells to the central nervous system. Emerging biomarker being assessed for use in MS monitoring and management. |
| Glial fibrillary acidic protein (GFAP) | A filament in astrocytes, which are cells that support neurons. Released into the spinal fluid and blood following a brain injury, GFAP is a newer biomarker being evaluated for its role in monitoring MS. |
| JCV antibody testing | Test for antibodies to the John Cunningham virus, or JCV, which in rare cases can lead to a potentially fatal inflammatory brain condition known as progressive multifocal leukoencephalopathy (PML). Used to determine a person’s status when considering starting certain disease-modifying therapies whose immunosuppressive effects may increase risk for PML in people with JCV antibodies. |
| MOG-IgG | Test for antibodies to myelin oligodendrocyte glycoprotein (MOG). Positive result can indicate that a person experiencing a demyelinating event has myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) rather than MS. |
| Kappa free light chains (kFLCs) | Small proteins in immunoglobulins. Levels can be increased due to chronic inflammation in the central nervous system, as occurs in MS and other neurologic conditions. |
| Neurofilament light chain (NfL) | Proteins released into the cerebrospinal fluid and blood following damage to axons – the projections at the end of nerve cells that transmit electrical impulses. Serum levels of NfL can be used to predict MS outcomes and monitor response to therapy. |
| Oligoclonal bands | Clusters of immunoglobulin proteins in the CSF that can indicate chronic inflammation. Elevated levels support a diagnosis of MS after considering other possible causes. |