MS: Genetic predisposition alone does not lead to the disease
In multiple sclerosis (MS), the cells of the immune system turn against their own body and attack the central nervous system. There is still no cure for the autoimmune disease. In a twin study, researchers may have discovered the cellular big bang of MS.
Scientists from the University of Zurich (UZH) and the LMU Klinikum Munich have examined the immune system of identical twin pairs to unravel the influence of environment and genetics on MS. The researchers may have discovered progenitor cells of the disease-causing T cells.
Cause still unclear
Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system, is the most common cause of neurological impairment in young adults. With the disease, your own immune system attacks your brain and spinal cord.
This leads to mostly progressive neurological dysfunctions such as visual disturbances, sensory disturbances, motor deficits (e.g. limitation of the ability to walk) as well as cognitive limitations.
Although the cause of MS is still unknown, a variety of genetic risk factors and environmental factors have been linked to the disease.
Genetic risk variants linked to MS development
Studies in recent years have clearly shown that genetic risk variants are inextricably linked to the development of MS.
“Through our study, we were able to show that approximately half of the composition of our immune system is determined by genetics,” explains Dr. Florian Ingelfinger, doctoral student at the Institute for Experimental Immunology at the University of Zurich, in a Message.
The new study, published in the journal “Nature” has been published.
According to the information, 61 identical – i.e. genetically identical – twin pairs were examined in this study, of which one twin suffers from MS and the other twin is healthy.
“Although the healthy twins also carry a maximum familial risk for the occurrence of MS, there were no clinical signs of MS in them,” says PD Dr. medical Lisa Ann Gerdes, neuroimmunologist at the Institute for Clinical Neuroimmunology at the LMU Klinikum and head of the MS TWIN STUDY.
Genetic influences could be excluded
Thanks to this unique cohort of identical twin pairs, genetic influences could be excluded when comparing twins with and without MS.
“We dare to tackle the central question of how the immune system of two genetically identical individuals can lead to this clear inflammatory reaction and massive nerve damage in just one case, while the other twin is not damaged at all,” says Prof. Becher from the Institute for Experimental Immunology at UZH.
This allows the team to track the changes in the immune system that ultimately trigger MS in a twin in a targeted manner and free of genetic influences, while the twin sister or twin brother is spared the disease.
Greater activation of T cells
The researchers use the latest technologies to describe the so-called immune profiles of the twin pairs in great detail.
“Amazingly, we found the greatest differences in the immune profiles of sick twins in so-called cytokine receptors, i.e. in the way in which immune cells communicate with each other. The cytokine network is the language of the immune system, so to speak,” explains Dr. finger finger
The scientists discovered that increased sensitivity to certain cytokines leads to greater activation of T cells in the blood of patients with MS. These are particularly capable of migrating into the central nervous system of the patient and causing damage there.
According to the release, the identified cells showed characteristics of recently activated cells that were in the process of developing into fully functional T cells. “We may have discovered the cellular big bang of MS here – progenitor cells from which disease-causing T cells develop,” says Prof. Becher.
better understand the origin of the disease
“The findings of this study are particularly valuable in comparison with previous studies on MS, which do not control for genetic predisposition,” emphasizes Prof. Becher.
“In this way, we decipher which part of the immune dysfunction in MS is influenced by genetic components and which by environmental factors. This is of fundamental importance in order to understand how the disease develops.”
The twin pairs were recruited for the study as part of the national MS TWIN STUDY at the Institute for Clinical Neuroimmunology at the LMU Klinikum in Munich.
“We owe the unique opportunity to decode genetics and environment in multiple sclerosis solely to our patients who have agreed to this study,” says PD Dr. Lisa Ann Gerdes. (ad)
Author and source information
This text corresponds to the specifications of medical specialist literature, medical guidelines and current studies and has been checked by medical professionals.
Swell:
- University of Zurich: Multiple sclerosis: twin study decodes influence of environment and genetics, (accessed: February 21, 2022), University of Zurich
- Florian Ingelfinger, Lisa Gerdes et al.: Twin study reveals non-heritable immune perturbations in multiple sclerosis; in: Nature, (veröffentlicht: 16.02.2022), Nature
Important NOTE:
This article contains general advice only and should not be used for self-diagnosis or treatment. He can not substitute a visit at the doctor.