Tracking the causes of multiple sclerosis by comparing the immune systems of twins

The Swiss MS Society provided us with its interim report upon their recent research initiative run by the Institute of Experimental Immunology at Zurich University (UZH). The University is investigating the extent to which genetic factors promote the development of multiple sclerosis, in a collaboration with doctors and scientists from the Ludwig Maximilian University (LMU) of Munich.

New research approaches

The cause of the disease is still unclear and is probably favored by a variety of environmental influences and genetic predispositions. Current therapies are very non-specific and sometimes have severe side effects.

“In order to develop more specific drugs, we are currently trying to identify the cell types that contribute to the development of the autoimmune reaction,” says Florian Ingelfinger,  doctoral student in the research group of Professor Burkhard Becher, Director of the Institute of Experimental Immunology and Member of the Scientific Advisory Group of the Swiss MS Society (SMSG) in the podcast, which he recorded as part of his doctoral thesis (available here in German language).

While more than 80 years of research have fundamentally improved our knowledge of the immune system, the transferability of findings from animal models to human multiple sclerosis, for example, is limited. For this reason, research has been carried out mainly on humans in recent years and the immune system of healthy people has been compared with that of MS patients.

Comparison of twin pairs

The research group led by Professor Burkhard Becher also takes this approach. “We want to find out how hereditary predisposition in combination with environmental factors contributes to the development of MS,” explains Ingelfinger. To eliminate human genetic variability and a large part of environmental factors, the UZH researchers are studying identical and non-identical twins, one of whom has MS and the other is healthy.

In order to find out which parts of the immune system are modulated by genetic factors and which are modulated by environmental influences, the research group has constructed a statistical model using a data set of healthy identical and non-identical twin pairs.

Artificial intelligence analysis

In order to get a detailed view of the twins’ immune system as possible, the research group uses mass cytometry (CyTOF). Individual immune cells are not labeled with fluorescent dyes as before, but with heavy metal ions instead. The marked immune cells are then fed into a plasma in which any biological material does burn – and only the heavy metal ions remain. The mass spectrometer can then be used to draw conclusions about the proteins of the immune cells. The result is a flood of data for more than 20 million cells.

“In order to identify possible patterns in the different types of immune cells, we use state-of-the-art artificial intelligence algorithms,” says Ingelfinger.

Genes do play an important role

By using such algorithms, the research group has now been able to identify a specific type of T-cell that divides much faster in the sick twins than in healthy ones, and which are more likely to attack the central nervous system. “Interestingly, these cells also show an unusual communication pattern, which has been observed so far in animal models of multiple sclerosis.” Another finding of the previous study, according to Ingelfinger, is that about 50 percent of the immune system is controlled by genetics. “So half of the functioning of our immune systems are owed to our parents,” Ingelfinger is convinced.

The study, promoted by Florian Ingelfinger is financially supported by the European Research Council (ERC) with € 2.5 million and is next to investigate the development of MS-like diseases (e.g. Neuromyelitis Optica) in order to be able to predict new so-called biomarkers for disease progression and therapy (success or failure) in the future. “Closing this gap in the treatment of MS,” says Ingelfinger, “would be the crowning achievement of a doctoral thesis.”

Translated from German original text (with minor adjustments) by Christoph Thalheim, with permission by Carlotta Superti-Furga, employee UZH News.