Scientists pinpoint antibodies which may drive MS

A new study suggests that antibodies directed against a protein found in both nerve cells and their supporting cells could play a part in driving multiple sclerosis (MS). Researchers looked at immune responses to over 23,000 human proteins and found that the MLC1 protein stood out as a key target for B-cells taken from people living with MS.

B-cells are a type of immune cell that produce antibodies. Although these antibodies are essential for fighting infections, it is thought that in MS some antibodies mistakenly attack healthy brain cells, triggering an immune response that can lead to nerve damage.

Previous work has identified several proteins that might be targeted in MS, including the brain protein GlialCAM, but there does not seem to be a single antigen common to all cases. Finding additional targets like MLC1 could help pave the way for more effective treatments.

In the study, researchers collected B-cells from 20 people living with MS and nine people without the condition. They exposed these cells to more than 23,000 different proteins. The results revealed that B-cells from people living with MS produced stronger antibody responses to various proteins, with MLC1 attracting particular interest.

MLC1 is present in nerve cells and astrocytes – the star-shaped cells that support nerve function. It is known to interact with GlialCAM. Alicia Weier, a doctoral student at the University of Bonn and one of the lead authors, explained that MLC1 is an interesting candidate because it is expressed on both astrocytes and neurons and works in partnership with GlialCAM.

Further analysis confirmed the original findings. People living with MS had higher levels of anti-MLC1 antibodies in both their blood and the fluid around their brain. These antibodies were also raised in samples from individuals with other inflammatory neurological conditions.

In the final phase of the study, the researchers injected anti-MLC1 antibodies into mice with an MS-like condition. The antibodies bound strongly to neurons in the brain’s outer layer and four out of the seven mice given the antibodies died within a day, while all the mice that did not receive the antibodies survived. The results suggest that anti-MLC1 antibodies may contribute to making the disease more severe.