Twin study identifies the role of genetics and environment in multiple sclerosis

Researchers from the University of Zurich, Munich’s LMU Klinikum hospital, have studied the immune system of monozygotic twins in order to determine the impact of genetics and the environment on multiple sclerosis. They may have found precursor cells for the disease-causing T cell cells.

Multiple sclerosis is a chronic inflammatory condition of the central nervous systems and is the leading cause for neurological impairment in young adults. MS occurs when the brain and spinal cord are attacked by the patient’s immune systems. This can lead to neurological deficits such damaged sight, sensory disturbances, motor problems, and other symptoms. Limiting the ability to walk and cognitive impairment. Although the cause is not yet known, MS has been linked to several environmental factors and genetic risk factors.

MS can’t be caused by genetic predisposition.

Recent studies have shown that multiple sclerosis can be caused by genetic risk variants. Florian Ingelfinger is a PhD candidate at UZH Institute of Experimental Immunology. “Based on our research, we were able… to show that approximately half of the composition of the immune system is determined through genetics,” he says. 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 Beltrán 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. The study examined 61 pairs of monozygotic monozygotic twins in which one twin was affected by MS and the other was healthy. The twins were therefore identical from a genetic perspective. Lisa Ann Gerdes explains that healthy twins also had the highest MS risk, but they showed no clinical signs.

Twin study eliminates genetic influences

This unique group of identical twins allowed researchers to exclude genetic influences through comparing twins with multiple sclerosis and those without. Burkhard Becher explains, “We are investigating the central question of whether the immune system of two genetically identical individuals causes significant inflammation and nerve damage in one case and no damage in the other.” The international team of scientists was able to use identical twins to determine if there was a genetic influence on MS and track the immune system changes that ultimately led to the onset of MS in one twin.

Artificial intelligence and single-cell technologies at the cutting edge

The twins’ immune profiles are described in great detail using state-of the-art technologies by the researchers. Florian Ingelfinger explained that the researchers use a combination o mass cytometry and modern genetics paired together with machine learning to not just identify the immunogenic proteins of the sick twin but also to decode all the genes that are activated in these cells. Eduardo Beltrán, an expert in single-cell genomics, adds: “This ensures that we obtain as much information as currently technically possible from these valuable samples.” To extract the relevant insights from this vast dataset, the team uses a variety customised algorithms that are based on artificial Intelligence.

An error in the communication with immune cells

“We were surprised to find that the cytokine-receptors are the areas where there are the greatest differences in immune profiles between MS-afflicted twins. The way that immune cells communicate with each other. Ingelfinger says that the cytokine network acts as the language of the immune systems. The researchers discovered that patients with multiple-sclerosis are more sensitive to certain cytokines and have higher activation rates of T cells in their blood. These T cells are more prone to migrate into patients’ central nervous systems and cause damage. The cells that were identified showed characteristics of newly activated cells. These cells were in the process to becoming fully functional T cells. Becher says, “We may have found the cellular big bang MS here – precursor cell that gives rise to disease-causing-T cells.”

Understanding the impact of genes and environment on MS is an important foundation

Burkhard Bercher states that “the findings of this research are especially valuable in contrast to previous MS studies that do not control genetic predisposition.” “We are now able to determine which part MS’ immune dysfunction is influenced more by genetic than environmental factors. This is crucial for understanding the pathogenesis of the disease. The LMU Klinikum recruited twins for the study. Lisa Ann Gerdes said, “This unique opportunity of unraveling the influence genetics and environment on multiple sclerosis was entirely thanks to our patients that agreed to join the study.”