Multiple sclerosis: Study with twins untangles environmental and genetic influences
Date:
February 16, 2022
Source:
University of Zurich
Summary:
Researchers have studied the immune system of pairs of monozygotic
twins to identify the influence of the environment and of genetics
in cases of multiple sclerosis. In the process, they may have
discovered precursor cells of the disease-causing T cells.
FULL STORY ========================================================================== Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and the most common cause of neurological impairment in
young adults. In MS, the patient's own immune system attacks the brain
and spinal cord, resulting in cumulative neurological deficits such as
damaged sight, sensory disturbances, motor deficits (e.g. limiting the
ability to walk) as well as cognitive impairment. Although the cause of
MS is still unclear, a variety of genetic risk factors and environmental influences have already been linked to the disease.
========================================================================== Genetic predisposition alone does not lead to MS Studies in recent years
have clearly shown that genetic risk variants are a necessary condition
for developing multiple sclerosis. "Based on our study, we were able
to show that about half of the composition of our immune system is
determined by genetics," says Florian Ingelfinger, a PhD candidate at the
UZH Institute of Experimental Immunology. The study by the team led by immunologist Burkhard Becher, professor at the Institute of Experimental Immunology at UZH, and the research groups of Lisa Ann Gerdes and Eduardo Beltra'n of the Institute of Clinical Neuroimmunology at the LMU Klinikum, shows that these genetic influences, while always present in MS patients,
are not on their own sufficient to trigger multiple sclerosis. In the
study, 61 pairs of monozygotic twins where one twin is affected by MS
whereas the co-twin is healthy were examined. From a genetic point of
view, the twins were thus identical.
"Although the healthy twins also had the maximum genetic risk for MS,
they showed no clinical signs of the disease," says Lisa Ann Gerdes.
Twin study eliminates genetic influences Thanks to this globally unique
cohort of identical twins, the researchers were able to exclude genetic influences by comparing twins with and without multiple sclerosis. "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," explains Burkhard Becher. Using identical twins enabled the international team of scientists
to rule out the genetic influence and specifically track the immune system changes that were ultimately responsible for triggering MS in one twin.
Cutting-edge single-cell technologies and artificial intelligence The researchers harness state-of-the-art technologies to describe the immune profiles of the twin pairs in rich detail. "We use a combination of
mass cytometry and the latest methods in genetics paired with machine
learning to not only identify characteristic proteins in the immune
cells of the sick twin in each case, but also to decode the totality of
all the genes that are switched on in these cells," Florian Ingelfinger explains. Eduardo Beltra'n, an expert in single-cell genomics, adds:
"This ensures that we obtain as much information as currently technically possible from these valuable samples." The team uses a variety of tailored algorithms based on artificial intelligence to extract relevant insights
from this immense dataset.
==========================================================================
An error in the communication of immune cells "Surprisingly, we found the biggest differences in the immune profiles of MS affected twins in to be
in the cytokine receptors, i.e. the way immune cells communicate with one another. The cytokine network is like the language of the immune system,"
says Ingelfinger. The researchers found that increased sensitivity to
certain cytokines leads to greater activation of T cells in the blood
of patients with multiple sclerosis. These T cells are more likely to
migrate into the central nervous system of patients and cause damage
there. The identified cells were found to have the characteristics of
recently activated cells, which were in the process of developing into
fully functional T cells.
"We may have discovered the cellular big bang of MS here -- precursor
cells that give rise to disease-causing T cells," says Becher.
Important foundation for understanding the influence of genetics and environment on MS "The findings of this study are particularly valuable
in comparison to previous studies of MS which do not control for genetic predisposition," says Burkhard Becher. "We are thus able to find out which
part of the immune dysfunction in MS is influenced by genetic components
and which by environmental factors. This is of fundamental importance
in understanding the development of the disease." The participating
twins were recruited for the study at the LMU Klinikum. "This unique opportunity to unravel the influence of genetics and environment in
multiple sclerosis is entirely thanks to our patients who agreed to join
the study," said Lisa Ann Gerdes.
Funding The study was supported by the Deutsche Forschungsgemeinschaft
within the framework of the German Excellence Strategy and the Munich
Cluster for Systems Neurology, as well as by the Gemeinnu"tzige Hertie Stiftung, the Bayerischer Landesverband der Deutschen Multiple Sklerose Gesellschaft (DMSG), the Bundesverband der DMSG, the Dr. Leopold und
Carmen Ellinger Stiftung, the Verein zur Therapieforschung fu"r MS
Kranke e.V., the Swiss National Science Foundation, the Studienstiftung
des deutschen Volkes and the European Research Council (ERC) under the
European Union's Horizon 2020 research and innovation programme.
special promotion Explore the latest scientific research on sleep and
dreams in this free online course from New Scientist -- Sign_up_now_>>> ========================================================================== Story Source: Materials provided by University_of_Zurich. Note: Content
may be edited for style and length.
========================================================================== Journal Reference:
1. Florian Ingelfinger, Lisa Gerdes et al. Twin study reveals
non-heritable
immune perturbations in multiple sclerosis. Nature, 16 February
2022 DOI: 10.1038/s41586-022-04419-4 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/02/220216112303.htm
--- up 10 weeks, 4 days, 7 hours, 13 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)