• Multiple sclerosis: Study with twins unt

    From ScienceDaily@1:317/3 to All on Wed Feb 16 21:30:48 2022
    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

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