Antibodies that destroy myelin in multiple sclerosis may cross-react with casein, a milk protein.

Multiple sclerosis (MS) is a neurodegenerative and autoimmune disease caused when the immune system attacks myelin proteins on nerves, mistaking them for proteins produced by pathogens. The cause of this immune confusion is complex but may involve exposure to proteins found in cow’s milk, which anecdotally worsen MS symptoms for some patients. New research supports this anecdotal evidence, finding that MS autoantibodies cross-react with casein, the principal protein in cow’s milk.

In order to create antibodies that react to new pathogens, B cells (a type of immune cells) use somatic hypermutation, a process during which they intentionally mutate regions of their DNA involved in antibody production. These rapid mutations are needed to increase antibody repertoire, the collection of an individual’s B cell receptor and antibody sequences; however, somatic hypermutation can result in the creation of autoantibodies, which bind to self-proteins produced by the body. While autoimmune B cells are usually destroyed shortly after creation, lingering autoimmune cells can proliferate and lead to diseases such as type 1 diabetes, rheumatoid arthritis, and MS. One reason autoantibodies persist is cross-reactivity with other proteins, such as those produced by pathogens or absorbed from the diet, especially in cases where gut leakiness increases the introduction of new proteins to the blood.

The investigators gave one group of mice an injection of casein with adjuvants, which are compounds added to vaccines to increase the body’s antibody response. To compare casein to other milk proteins, they also immunized one group of mice with alpha-lactalbumin and another with beta-lactoglobulin, both whey proteins, for a total of three mouse groups. Changes in behavior and nerve degeneration were observed at 13, 20, or 40 days after immunization. The researchers also collected blood samples from 39 patients with MS and 23 patients with other neurological diseases in order to test for cross-reactivity of autoantibodies with casein.

Mice immunized with casein exhibited a range of MS symptoms such as weakness and disorientation, while mice immunized with whey proteins did not. Immunization with casein led to a progressive increase in casein-reactive antibodies and deterioration of myelin in nerves of the lower spinal cord. The researchers found that casein-immunized mice produced autoantibodies that cross-react with myelin-associated glycoprotein (MAG), a protein produced by nerve cells called oligodendrocytes, which have a similar structure to casein. Finally, they found that 42 percent of participants with MS had casein-reactive antibodies compared to only 28 percent of participants with other neurological disorders.

While it is not clear from these results what role dairy consumption plays in the development of MS, the authors suggest that some patients with MS may benefit from restricting dairy in their diet.

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