Several biomarkers for diagnosis of multiple sclerosis, disease evolution and response to medication (current or expected) are under research.
They are expected to play an important role in the near future of MS.[3] Biomarkers can be classified according to several criteria.
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[13] About biomarkers for MRI images, Radial Diffusivity has been suggested as a biomarker associated with the level of myelination in MS lesions.
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.
[14] Glial fibrillary acidic protein (GFAP) has been indicated as a possible biomarker for the progression of MS.
[15] Currently the only clear biomarker that predicts a response to therapy is the presence of anti-MOG autoantibodies in blood.
Comparative Effectiveness Research (CER) is an emerging field in Multiple Sclerosis treatment.
A good example could be the discovery that the presence of a gene called SLC9A9 appears in people who fail to respond to interferon β therapy[18][19] or that the disregulation of some transcription factors define molecular subtypes of the disease[20] Other good example could be the Hellberg-Eklund score for predicting the response to Natalizumab.
For an example about research in this area, it has been found that fingolimod is specially suitable for patients with frequently relapsing spinal cord lesions with open-ring enhancement.
[28] The presence of anti-MOG, even with CDMS diagnosis, can be considered as a biomarker against MS disease modifying therapies like fingolimod.
[31] As of 2014 no biomarker with perfect correlation has been found,[32] but some of them have shown a special behavior like IgG- and IgM- oligoclonal bands[33][34] in the cerebrospinal fluid and autoantibodies against neurotropic viruses (MRZ reaction) [35] and the potassium channel Kir4.1.
Currently it has been proposed the protein SLC9A9 (gen Solute carrier family 9) as biomarker for the response to interferon beta.
[54] There is also an overexpression of IgG-free kappa light chain protein in both CIS and RR-MS patients, compared with control subjects, together with an increased expression of an isoforms of apolipoprotein E in RR-MS.[55] Expression of some specific proteins in circulating CD4+ T cells is a risk factor for conversion from CIS to clinically defined multiple sclerosis.
There is current evidence that at least 60 circulating miRNAs would be dysregulated in MS patient's blood and profiling results are continuously emerging.
Circulating miRNAs are highly stable in blood, easy to collect, and the quantification method, if standardized, can be accurate and cheap.
Blood circulation is slower in MS patients and can be measured using contrast[70] or by MRI[71] Interleukin-12p40 has been reported to separate RRMS and CIS from other neurological diseases[72] The most specific laboratory marker of MS reported to date, as of 2016, is the intrathecal MRZ (Measles, Rubella and Varicella) reaction showing 78% sensitivity and 97% specificity.
This observation has been linked to the activity of the infiltrating leukocytes and activated microglia, and to the damage to the axons[76] and to the oligodendrocytes damage, supposed to be the main cleaning agents for glutamate[77] Also a specific MS protein has been found in CSF, chromogranin A, possibly related to axonal degeneration.
[80] Plasma Cells in the cerebrospinal fluid of MS patients could also be used for diagnosis, because they have been found to produce myelin-specific antibodies.
This showed that some patients diagnosed with PPMS shared an inflammatory profile with RRMS and SPMS, while others didn't.
The pre-active lesions are clusters of microglia driven by the HspB5 protein, thought to be produced by stressed oligodendrocytes.
[94] Retinal cells are considered part of the CNS and present a characteristic thickness loss that can separate MS from NMO[95] Currently it is possible to distinguish between the three main clinical courses (RRMS, SPMS and PPMS) using a combination of four blood protein tests with an accuracy around 80% [96] Currently the best predictor for clinical multiple sclerosis is the number of T2 lesions visualized by MRI during the CIS, but it has been proposed to complement it with MRI measures of BBB permeability[97] It is normal to evaluate diagnostic criteria against the "time to conversion to definite".
Magnetic resonance (MRI) and positron emission tomography (PET) are two techniques currently used in MS research.
Serum TNF-α and CCL2 seem to reflect the presence of inflammatory responses in primary progressive MS.[105] As previously reported, there is an antibody against the potassium channel protein KIR4.1[36] which is present in around a half of MS patients, but in nearly none of the controls, pointing towards a heterogeneous etiology in MS.