Twin study shows origin of multiple sclerosis

In a study that is unparalleled worldwide, researchers at the University of Zurich (UZH) and the Ludwig-Maximilians University Munich (LMU) have discovered the influence of environmental factors in the development of multiple sclerosis (MS). According to a report from the UZH, the study investigated a cohort of monozygotic (identical) twins compiled by the LMU, where each pair had one twin with the illness and one healthy twin.

This meant that they were able to concentrate on the changes to the immune system while excluding genetic factors. Immunologist Burkhard Becher, professor at the Institute of Experimental Immunology at UZH, explains the study design: “We are exploring the central question of how the immune system of two genetically identical individuals leads to significant inflammation and massive nerve damage in one case, and no damage at all in the other.”

Using mass cytometry, the latest approaches in genetics, and machine learning, the team was not only able to identify characteristic proteins in the immune cells of the affected twins, but also to decode the entirety of all genes that are switched on in these cells. Florian Ingelfinger, a PhD candidate in the team led by Becher, states that “surprisingly” the biggest differences were found in the cytokine receptors, i.e. “the way immune cells communicate with one another”.

The researchers discovered that an increased sensitivity toward certain cytokines leads to greater activation of T cells in the blood. These are particularly effective at entering the central nervous system in humans and causing damage there. The identified cells had the characteristics of recently activated cells in the process of developing into fully functional T cells. Becher adds: “We may have discovered the cellular big bang of MS here – precursor cells that give rise to disease-causing T cells.”