Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS) that disrupts communication from the body to the brain. It’s characterized by the inflammation and demyelination of nerve cells found in the brain, spinal cord, vision and muscles. Changes in the cerebral spinal fluid (CSF) is an indicator of inflammation, and disruption in the blood brain barrier (BBB) for MS patients.¹ In a paper recently published in A Journal of Neurology, Goris et al., investigates the possible biomarkers of MS to determine the presence of immunoglobulin G (IgG) and oligoclonal bands (OCB) in the CSF, in patients from different demographics and genders. With a disease so aggressive and no possible cures, diagnosis is not always a straightforward process so multiple reliable biomarkers are needed to monitor and diagnose patients with MS to prevent misdiagnosis. 

Background

There are many molecular biomarkers used in identifying patients with MS, but specific test detecting antibodies, and the use of magnetic resonance imaging to detect brain and spinal cord lesion are frequently used.² MS patients contain an increase in IgG levels and the findings of OCB in the CSF^3,4. Patients with MS were analyzed from nine different countries to investigate genetic and ethnicity factors by combining genome wide single nucleotide polymorphism (SNP).³  

Methods

Patients included in this study were analyzed and screened for MS with an MRI and a spinal puncture used for DNA sequence to determine the presence of OCB and IgG. 6950 patients from nine different countries, were used in this study to screen and analyze genetic factors involved by genotyping. The cells were screened and replicated into SNP data for testing of common human leukocyte antigens (HLA) genes in the CSF.³ The presence of antibodies in the CSF is not the only evidence shown in MS patients, the loss of brain cells and grey matter are evident in patients by using an MRI to assess the damage.⁵ The use of proton magnetic resonance spectroscopy (1H-MRS) is also used to measure alterations in lesions, gray and white matter of the brain and the spinal cord.⁶ Other possible biomarkers used to determine MS but not as popular is through the extraction of RNA from red blood cells that are able to get through the BBB and initiate destruction of nerves.¹

Results

Researchers found that Increase in IgG was highly associated with OCB presence, and gender was also correlated with the presence of both biomarkers. Females had a higher IgG index and OCB positive than in males. OCB positivity was found in 88% and high IgG index in 64% of patients with MS. Patients with higher IgG index and OCB status had a higher severity score of MS are usually found higher in females than in males. The presence of OCB is associated with an increase in disease activity and a greater risk for brain deterioration.⁷ 

Possible therapies for MS is the use of mesenchymal stem cells (MSC) in tissue protection by the encouraging re-myelination in damaged cells of the brain.⁸ Stem cell research is a growing treatment that can be used to repair damaged cells. Other treatments include INF therapy, which is associated with anti-inflammatory used in delaying the migration of T-cells across the BBB, which causes inflammatory and damage to axons and myelin sheaths.⁹ In addition to pharmacological treatments, rehabilitation is recommended to optimize daily functions in motility, communication and daily functions. The use of physical therapy (PT) can help improve physical functions, muscle power and pain levels.¹⁰ 

 This study investigates large genetic differences, the presence of IgG and OCB status in different demographics in patients with MS. Inflammation in the brain is reflected by alterations in the CSF which may correlate with disease progression. Researching large data sets of patients in different demographics is useful in determining gender correlation and genetic variations. Many factors continue misdiagnosis that can increase harm and prolong adequate treatment needed, for example the presence of OCB in CSF is not limited to MS, but can also indicate a variety of chronic inflammatory diseases which can pose as a problem in diagnosing. Other biomarkers should be used in assessing MS in patients such as MRI scans and 1H-MRS as they show the presence of lesions and any alterations in the brain and spinal cord. Researching accurate biomarkers for MS is a growing research topic that will not only benefit the science industry but help patients be diagnosed properly and be treated early. 

Figure 1 

Figure Legend: Possible biomarkers used to diagnose patients with MS, and possible therapies to help reduce inflammation and improve cell and physical function. 1. Magnetic resonance imaging, 2. Human leukocyte antigen, 3. Immunoglobulin G, 4. Oligoclonal bands, 5. Proton magnetic resonance spectroscopy, 6. Mesenchymal stem cells for multiple sclerosis, 7. Interferon β, 8. Physical therapy. 

[+] References

[+] Other Work By Deborah Rosca