Casein may contribute to MS developmentMarch 01, 2022
Cow's milk protein triggers autoimmune response, inducing neuronal damage in mice
Patients suffering from Multiple Sclerosis (MS) often complain of more severe disease symptoms after consuming dairy products. Researchers of the Cluster of Excellence ImmunoSensation2 at the University of Bonn, together with colleagues at the University of Erlangen-Nuremberg, have now found a possible cause for this: Casein, a protein in cow's milk, can trigger inflammation that damages myelin sheaths around nerve cells. The study was able to demonstrate this link in mice, but also found evidence of a similar mechanism in humans. The researchers therefore recommend that certain groups of affected individuals avoid dairy products. The study has now been published in the journal PNAS.
The prompt for the study came from MS patients: "We hear again and again from people affected by MS, that they feel worse when they consume milk, cottage cheese or yogurt," explains Stefanie Kürten from the Institute of Anatomy at University Hospital Bonn. "We are interested in the cause of this correlation."
The professor of neuroanatomy is considered a renowned expert on multiple sclerosis. She began the study in 2018 at the University of Erlangen-Nuremberg. A year and a half ago, she moved to Bonn, where she continued the work together with her research group. "We injected mice with different proteins from cow's milk," she says. "That way, we wanted to find out if there was a component to which they reacted with disease symptoms." The researchers did indeed find what they were looking for: When they administered the cow's milk constituent casein together with an enhancer substance to the animals, the mice went on to develop neurological disorders. Electron microscopy showed damage to the myelin sheaths.
In multiple sclerosis, the body's immune system destroys the myelin sheath of nerve fibers. The consequences range from paresthesia and vision problems to movement disorders. Also in the mice analyzed, the myelin sheath was massively perforated - apparently triggered by casein administration. "We suspected that the reason was a misdirected immune response, similar to that seen in MS patients," explains Rittika Chunder, who is a postdoctoral fellow in Prof. Kürten's research group. "The body's defenses actually attack the casein, but in the process they also destroy proteins involved in the formation of myelin."
Such cross-reactivity can occur when two molecules are very similar, at least in parts. The immune system then in a sense mistakes them for each other. "We compared casein to different molecules that are important for myelin production," Chunder says. "In the process, we came across a protein called MAG. It looks remarkably similar to casein in some respects - so much so that in the experimental animals, antibodies to casein were also active against MAG."
This means that in the casein-treated mice, the body's own defenses were also directed against MAG, destabilizing the myelin. But to what extent can the results be transferred to people affected by MS? To answer this question, the researchers added casein antibodies from mice to human brain tissue. These did indeed accumulate in the cells responsible for myelin production in the brain.
The study found that the B cells, responsible for antibody production, in the blood of people with MS respond particularly strongly to casein. Presumably, the affected individuals developed an allergy to casein at some point as a result of consuming milk. Now, as soon as they consume fresh dairy products, the immune system produces masses of casein antibodies. Due to cross-reactivity with MAG, these also damage the myelin sheath around the nerve fibers.
However, this only affects MS patients who are allergic to cow's milk casein. "We are currently developing a self-test with which affected individuals can check whether they carry corresponding antibodies," says Kürten. "At least this subgroup should refrain from consuming milk, yogurt, or cottage cheese."
It is possible that cow's milk also increases the risk of developing MS in healthy individuals. Because casein can also trigger allergies in them - which is probably not even that rare. Once such an immune response exists, cross-reactivity with myelin can in theory occur. However, this does not mean that hypersensitivity to casein necessarily leads to the development of multiple sclerosis, the professor emphasizes. This would presumably require other risk factors. This connection is nevertheless worrying, Kürten says: "Studies indicate that MS rates are elevated in populations where a lot of cow's milk is consumed."
In addition to the University of Bonn, the Friedrich-Alexander-Universität Erlangen-Nürnberg, Klinikum St. Marien Amberg and Stanford University School of Medicine were also involved. The study was funded by the German Research Foundation (DFG), the IZKF-ELAN program of the University of Erlangen-Nuremberg, and private donors.
Rittika Chunder et al.: Antibody cross-reactivity between casein and myelin-associated glycoprotein results in central nervous system demyelination with implications for the immunopathology of multiple sclerosis; PNAS DOI: https://doi.org/10.1073/pnas.2117034119
Prof. Dr. Stefanie Kürten
Institute of Anatomy
University Hospital Bonn