Research continues on BBB involvement in AE

April 1, 2020

The blood-brain barrier (BBB) is a highly selective barrier formed by endothelial cells connected by tight junctions that separate circulating blood from the brain. An intact BBB prevents many micro- and macromolecules and immune cells from entering the brain in order to protect and maintain an optimal level of essential nutrients and neurotransmitters. There has been growing evidence that BBB disruption is associated with brain inflammatory conditions such as Alzheimer’s disease, MS and AE. In AE, autoantibodies and immune cells gain access to the brain by crossing the BBB to cause inflammation. The underlying mechanisms are still poorly understood.

Illustration – Diana Molleda

The diagnosis of AE relies mostly on clinical symptoms and antibody testing. In many cases, the antibody test comes back negative.  Clinical symptoms may also mimic other diseases making diagnosis challenging. A group in Taiwan led by Dr. Sung-Chou Li is investigating new biomarkers that could be helpful for the diagnosis of AE and in facilitating the clinician’s decision to initiate prompt treatment. Their focus is on the S100A gene family as these genes are deeply involved in inflammation-related diseases.

In this study, the group used AE patient serum and a new in vitro BBB model to demonstrate that S100A6 promoted antibody-producing B cells to penetrate the BBB. S100A6 is a small calcium-binding protein and is involved in the regulation of cellular functions like proliferation and the cellular response to different stress factors.

Since DNA methylation (which changes the function of genes by adding a methyl-group to the DNA) plays important role in many autoimmune diseases, the group also conducted a genome-wide examination of DNA methylation to search for potential disease genes. They identified S100A6 and S100A11 as the candidate disease genes of AE.

Further studies are likely to improve our understanding of AE, particularly regarding how S100A6 protein facilitates B lymphocyte infiltration as well as possible other factors in AE serum that might contribute to this phenomenon. Hopefully, such studies will reveal novel therapeutic targets for the treatment of AE.

You can read the full article here