Neuroscience and Neurology

Identical twin study reveals non-heritable immune perturbations in multiple sclerosis

Dr. Florian Ingelfinger

Universität Zürich
Universitätsspital Zürich

Multiple sclerosis (MS) is the most common cause of neurological deficits in young adults. In Switzerland, more than 10’000 people are currently living with this disease. Both, genetic risk factors and environmental triggers, contribute to the immune-mediated destruction of the patients’ own central nervous system. However, it remains unknown how specifically heritable and non-heritable influences shape the immune system to ultimately elicit MS.

The aim of the study of Florian Ingelfinger and his colleagues was to dissect how genetic and environmental risk factors affect the immune system in MS patients and facilitate the immune-mediated disability. The scientists analyzed circulating immune cells of 61 genetically identical twin pairs, in which one twin was affected by MS and the other twin did not show any signs of the disease despite having the same genetic risk for MS. 

Florian Ingelfinger and his team used state-of-the-art technology to describe the immune profiles of the twin pairs. They exerted a combination of mass cytometry and modern methods in genetics paired with artificial intelligence to uncover characteristic proteins in the immune cells of the sick twins. Moreover, they identified all the genes that were activated in these cells. The most pronounced differences in the immune profiles of twins affected by MS were found regarding intercellular communication: The scientists observed an increased sensitivity to certain cytokines (molecules that are used by the immune system for intercellular communication) that was associated with a stronger activation of T cells in the blood of patients with MS. These T cells were more likely to migrate into the central nervous system of patients and cause damage there.

The findings of this study with identical twins indicate that environmental stimuli cause an imbalance in the communication circuits of leukocytes during the development of MS. In combination with a genetic predisposition in patients, this imbalance could lead to the activation of pathogenic T cells and thus to the development of MS. These insights are fundamental to understand how genetics and environmental factors predispose to MS and can contribute to the development of novel therapeutic approaches.

Twin study reveals non-heritable immune perturbations in multiple sclerosis. Florian Ingelfinger*, Lisa Ann Gerdes*, Vladyslav Kavaka 3 4, Sinduya Krishnarajah, Ekaterina Friebel, Edoardo Galli, Pascale Zwicky, Reinhard Furrer, Christian Peukert, Charles-Antoine Dutertre, Klara Magdalena Eglseer, Florent Ginhoux, Andrea Flierl-Hecht, Tania Kümpfel, Donatella De Feo, Bettina Schreiner, Sarah Mundt, Martin Kerschensteiner, Reinhard Hohlfeld, Eduardo Beltrán, Burkhard Becher. Nature. 2022 Mar;603(7899):152-158.
* Contributed equally