Investigators at Stanford University and their collaborators have identified a mechanism for how the Epstein-Barr virus (EBV), a known risk factor for multiple sclerosis, may prompt the immune system to attack brain cells to trigger MS. In a study published in
Nature, antibodies derived from cells in the spinal fluid were shown to recognize and bind to a component of EBV and also shown to recognize and bind to a similar molecule on brain cells that have been implicated in MS. This suggests that the molecule on brain cells mimics the structure of the EBV component and can set off an autoimmune process.
This study follows a
recent announcement of new proof that EBV infection occurs in advance of the onset of MS and acts with other risk factors to cause the disease. Both studies provide a firm rationale for developing therapies and vaccines to thwart EBV and potentially stop MS or prevent its onset.
Background
- EBV: The Epstein-Barr virus is spread primarily through contact with infected saliva. It is very common, and most people are infected by it, generally without harm, in childhood. In adolescence and adulthood, it can cause infectious mononucleosis, a disease that increases the risk of later developing MS. The virus stays in the body throughout a person’s lifetime, and has been linked to certain cancers and autoimmune diseases. There is currently no treatment that can eliminate the virus from a person’s system.
Details of the Study
- Through a series of steps, researchers led by Dr. William Robinson found evidence that up to one-fourth of people with MS had antibodies circulating in the blood and spinal fluid that recognized and bound to both a product of the EBV virus and a component of the brain cells that produce myelin, the nerve-insulating sheath that is a key target of immune attacks and destruction in MS.
- This “cross-reactivity” means that when the immune system is doing its job to try to fight EBV, it may also attack myelin-making cells. The team further evaluated this scenario by introducing the segment of EBV into mice with an MS-like disease, which made it worse.
- This study was supported in part by a special initiative in which the JDRF, Lupus Research Alliance, and National MS Society joined forces to identify common mechanisms of autoimmunity.
- This and other studies provide the rationale for developing therapies and vaccines that target EBV. Importantly, this study suggests that any EBV vaccine to be developed should not include the particular EBV component (EBNA1) that might cross-react and cause an autoimmune reaction to myelin-making cells.
“Clonally Expanded B Cells in Multiple Sclerosis Bind EBV EBNA1 and GlialCAM,” by Tobias V. Lanz, R. Camille Brewer, Peggy P. Ho, Jae-Seung Moon, Kevin M. Jude, Daniel Fernandez, Ricardo A. Fernandes, Alejandro M. Gomez, Gabriel-Stefan Nadj, Christopher M. Bartley, Ryan D. Schubert, Isobel A. Hawes, Sara E. Vazquez, Manasi Iyer, J. Bradley Zuchero, Bianca Teegen, Jeffrey E. Dunn, Christopher B. Lock, Lucas B. Kipp, Victoria C. Cotham, Beatrix M. Ueberheide, Blake T. Aftab, Mark S. Anderson, Joseph L. DeRisi, Michael R. Wilson, Rachael J. M. Bashford-Rogers, Michael Platten, K. Christopher Garcia, Lawrence Steinman & William H. Robinson, was published in
Nature on January 24, 2022.