Several biomarkers for diagnosis of multiple sclerosis, disease evolution and response to medication (current or expected) are under research. While most of them are still under research, there are some of them already well stablished:
oligoclonal bands: They present proteins that are in the CNS or in blood. Those that are in CNS but not in blood suggest a diagnosis of MS. MRZ-Reaction: A polyspecific antiviral immune response against the viruses of measles, rubella and zoster found in 1992. In some reports the MRZR showed a lower sensitivity than OCB (70% vs. 100%), but a higher specificity (69% vs. 92%) for MS. free light chains (FLC). Several authors have reported that they are comparable or even better than oligoclonal bands.
They can be of several types like body fluid biomarkers, imaging biomarkers or genetic biomarkers. They are expected to play an important role in the near future of MS.
Classification
Biomarkers can be classified according to several criteria. It is common to classify them according to their source (imaging biomarkers, body fluid biomarkers and genetic biomarkers) or their utility (diagnosis, evolution and response to medication)
Among the imaging biomarkers in MS the most known is MRI by two methods, gadolinium contrast and T2-hypertense lesions, but also important are PET and OCT.
Among the body fluid biomarkers the most known are oligoclonal bands in CSF but several others are under research.
Genetic biomarkers are under study but there is nothing conclusive still.
Addressing the classification by its utility we have diagnosis biomarkers, evolution biomarkers and response to medication biomarkers.
Biomarkers for diagnosis
Apart from its possible involvement in disease pathogenesis, vitamin D has been proposed as a biomarker of the disease evolution.
Diagnosis of MS has always been made by clinical examination, supported by MRI or CSF tests. According with both the pure autoimmune hypothesis and the immune-mediated hypothesis, researchers expect to find biomarkers able to yield a better diagnosis, and able to predict the response to the different available treatments.
As of 2016 no specific biomarker for MS has been found, but several studies are trying to find one. Some researchers are focusing also in specific diagnosis for each of the clinical courses
Some people focus on blood tests, given the easy availability for diagnosis. Among the studies for blood tests, the highest sensitivity and specificity reported to date is testing circulating erythrocytes (s=98.3%, e=89.5%). Also a good result was obtained using methylation patterns of circulating cell debris are specific for a number of conditions, including RRMS There are ongoing efforts to be able to diagnose MS by analysing myelin debris into the blood stream.
As of 2014, the only fully specific biomarkers found were four proteins in the CSF: CRTAC-IB (cartilage acidic protein), tetranectin (a plasminogen-binding protein), SPARC-like protein (a calcium binding cell signalling glycoprotein), and autotaxin-T (a phosphodiesterase) This list was expanded in 2016, with three CSF proteins (Immunoglobulins) reported specific for MS. They are the following immunoglobulins: Ig γ-1 (chain C region), Ig heavy chain V-III (region BRO) and Ig-κ-chain (C region)
For existing damage and disease evolution
During a clinical trial for one of the main MS drugs, a catheter was inserted into the brain's ventricles of the patients. Existing damage was evaluated and correlated with body fluids. Thanks to the courage of these volunteers, now we know that in PPMS, neurofilament light chain (NF-L) level, in CSF and serum, is a sensitive and specific marker for white matter axonal injury
About biomarkers for MRI images, Radial Diffusivity has been suggested as a biomarker associated with the level of myelination in MS lesions. However, it is affected also by tissue destruction, which may lead to exaggeration of diffusivity measures. Diffusivity can be more accurate. Distinct patterns of diffusivity in MS lesions suggest that axonal loss dominates in the T1 hypointense core and that the effects of de/remyelination may be better detected in the "T2-rim", where there is relative preservation of structural integrity.
Glial fibrillary acidic protein (GFAP) has been indicated as a possible biomarker for the progression of MS. The blood level of GFAP increases when astrocytes are damaged or activated, and elevated levels of the protein's cellular component correlate with severity of MS symptoms.