TO trigger multiple sclerosis, genetics are not enough. It is necessary, yes, but by itself it is not enough. The “Big Bang” that causes the disease is in fact a bad communication between the cells of the immune system, which are then activated in an excessive way and cause damage to the central nervous system. The discovery comes from a study that compared 61 pairs of homozygous twins, that is, they share the same genetic heritage, in which only one of the two developed multiple sclerosis. “To our surprise we saw that the biggest difference between the twin’s immune systems was in the cytokine receptors, which are the substances that immune cells use to communicate with each other. The cytokine network can be considered the language of the immune system “, explained Florian Ingelfinger of the Institute of Experimental Immunology at the University of Zurich, who together with Lisa Ann Gerdes and Eduardo Beltrán of the Ludwig Maximilian University of Munich led the study published today on the pages of Nature.
The relative importance of genetics
In recent years there have been several studies that have demonstrated the fundamental role of some genetic risk factors in the development of this inflammatory disease, in which the immune system, as if “mad”, affects the brain and spinal cord leading to cognitive deficits and engines. However, none of these alone is enough to trigger the disease. So much so that even today the causes of MS are unknown. Now, thanks to this truly unique sample of volunteers, it has been possible to understand how the immune systems of two genetically identical individuals can cause massive damage to the nervous system in one case, and nothing in the other. “Although healthy twins also carry the genetic variant in their DNA that is a risk factor for the disease, they do not show any signs of it,” noted Gerdes. This allowed genetic factors to be excluded from the equation and to focus exclusively on environmental ones. “We used the most advanced techniques in the field of genetics, combined with artificial intelligence algorithms – continues Gerdes – to identify not only the characteristics of immune cells, but also to decode all the genes that are active within these cells”.
A communication error
So what is it that triggers the disease? A communication error caused by an increased sensitivity of some cytokines – molecules involved in the processes of inflammation – which leads to an excessive activation of the T cells of the immune system present in the blood of people with MS. These cells (which have the characteristics of cells that are becoming fully functional) take their way into the central nervous system and cause damage there. “We may have discovered the cellular Big Bang of multiple sclerosis,” said Burkhard Becher of the University of Zurich and leader of the international group that conducted the research: “These cells are ready to turn into enemies of the body.”
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