In multiple sclerosis, the immune system goes rogue, mistakenly attacking the brain and spinal cord tissues. The debilitating result of this cellular assault includes the loss of mobility and cognitive impairment. Despite years of research, neuroscientists are still unclear about the exact cause of MS. However, they have pinpointed certain genetic and environmental factors as being critical.
In a recent study published in the journal Nature, a team of researchers looked at the genetics of twins for more insights into MS drivers. They recruited a cohort of 61 monozygotic twins where one of the pair had received an MS diagnosis while the other was healthy. Genetically, the twins were identical. But, despite having the maximum risk of developing MS (at least using current theoretical frameworks), the healthy twin showed no clinical signs of having the condition.
This experimental model is particularly unique, as researchers were able to exclude the possibility of genetic influences and zero in on the differences in the twins' immune systems. To achieve this, the researchers used a combination of techniques such as single-cell genetic analyses powered by artificial intelligence and mass cytometry, which enabled them to deeply profile immune cells on a molecular level. Their work generated a massive dataset, which the team had to build custom machine learning algorithms to parse through the data and extract patterns.
"Surprisingly, we found the biggest differences in the immune profiles of MS affected twins in to be in the cytokine receptors," said Florian Ingelfinger, one of the researchers on the study, adding that cytokines are how immune cells communicate with each other. "The cytokine network is like the language of the immune system."
The twin with MS was found to have T cells that were hypersensitive to specific cytokines, activating more cells and increasing the chances that they would migrate into the central nervous system and wreak havoc there. The team also discovered a unique subset of precursor T cells in these patients, which they demonstrated give rise to MS-causing immune cells.
According to the researchers, these results have transformed our current understanding of the genetic and environmental influences of MS development. The team expressed their gratitude for the study participants who enabled this breakthrough finding.