Researchers from Linköping University (Linköping, Sweden) have potentially discovered novel diagnostic biomarkers for multiple sclerosis (MS) by utilizing in vitro activation of patient-derived CD4+ T cells. Identifying these potential biomarkers will assist clinicians in determining the severity of the disease and therefore may provide the patient with personalized treatment.
The study, recently published in Cell Reports, may lead to the development of a clinically useful screening test in personalized MS treatment, which is highly required given the variable disease course and responses to current treatment.
Due to the chronic inflammatory nature of the central nervous system in MS, individuals display differing responses to treatment and levels of disease severity, therefore identification of biomarkers would provide a considerable aid in personalized treatment for the patient.
However, establishing potential biomarkers is difficult due to the complexity of the disease process.
For the investigation, the researchers compared the immune response from MS patients to healthy individuals to discern relevant genes that could translate to clinically valuable MS biomarkers. The team concentrated attention on CD4+ T cells due to their early regulation in adaptive immunity and observed a dysregulated response in patient derived CD4+ T cells.
By integrating their results with genome-wide association studies, the team was able to discover significant proteins in MS. They were able to identify four proteins that are measureable in cerebrospinal fluid and were able to utilize these biomarkers to classify patients from control individuals.
Additionally, the researchers could use these measurements to predict disease activity after 2 years and distinguish the response to natalizumab treatment in two small cohorts.
Further research and validation is still required but these biomarkers have demonstrated the potential to be implemented in a clinical setting.
“A key finding is that a combined protein score of CXCL1-3, CXCL10, CCL2, and OPN, measured in CSF, was able not only to discriminate early MS from controls … but also to predict evidence of disease activity after 2 years, a most valuable finding when deciding treatment strategies,” the researchers commented.
The researchers concluded: “Of note, the combined score … was also able to predict low or high response to treatment, which suggests that proteins relevant to the disease process are also important for the response to treatment, further strengthening the potential use of the combined score in personalized treatment.”
Sources: Hellberg S, Eklund D, Gawel DR et al. Dynamic Response Genes in CD4+ T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis. Cell. Rep., doi: 10.1016/j.celrep.2016.08.036 (2016) (Epub ahead of print);https://multiplesclerosisnewstoday.com/2016/09/23/multiple-sclerosis-biomarker-may-predict-disease-progression-treatment-response