February 4, 2022

A potential new cause of the autoimmune disease multiple sclerosis (MS) was discovered by researchers partly funded by the Lupus Research Alliance. Published in the prestigious journal Nature, the study results provide strong evidence that a virus can trigger the development of MS. The LRA invested in this work to help understand the connection between viruses and autoimmune diseases including lupus. This LRA funding is associated with the Common Mechanisms in Autoimmunity grant partnership with the JDRF and National Multiple Sclerosis Society to support innovative research exploring commonalities and differences in the immune system that drive distinct autoimmune diseases.

The research was led by the LRA grantee William Robinson, MD, PhD, a Professor of Medicine and Chief of the Division of Immunology and Rheumatology at Stanford University and a Staff Physician at VA Palo Alto. Dr. Robinson’s clinical research laboratory investigates the development of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. His goal is to demonstrate various causes of autoimmune diseases, and to leverage these findings to advance prevention strategies and novel treatments for patients.

Identifying a Cause of Multiple Sclerosis
The research field has long thought that viruses may cause autoimmune diseases. However, the science has not been clear and definitive causes of autoimmunity have remained a mystery. The current research findings from the Robinson laboratory show that the Epstein-Barr virus (EBV) may be the cause of MS in some patients.

EBV is a common type of herpes virus that generally infects most people during their teenage years.  In some individuals it causes infectious mononucleosis, also known as “mono” or “kissing disease”.  However, the latest research from Dr. Robinson and his team shows that in some people the immune system becomes confused and generated immune responses that target both EBV and proteins in the myelin sheath – the insulating layer around nerves that allows electrical impulses to transmit quickly along the nerve cells.

The research team initially analyzed antibodies from spinal fluid, that are detected in routine diagnostic tests for evaluation of MS. They showed that a unique type of antibodies, called oligoclonal bands, were produced by B cells in the spinal fluid of MS patients but not healthy individuals. B cells are a type of immune cells responsible for producing antibodies, which play a key part in immunity.

Establishing the Connection Between MS and EBV
Proteins produced by viruses that mimic proteins in the body can confuse the immune system. Dr. Robinson and colleagues found that when a person is infected with EBV, the person’s immune system tries to clear the virus by producing antibodies against it. However, in some patients with MS the anti-EBV response cross-reacts with the myelin sheath.  This cross-reactive immune response damages the insulating myelin sheath layer around nerves and thereby causes MS. When the insulating myelin sheath is damaged, the nerve electrical signals cannot properly travel, which leads to debilitating symptoms. The immune attack happens because the immune system produces antibodies that crossreact with an EBV protein called EBNA1 and the body’s own glial cell adhesion molecule (GlialCAM), which is expressed by glial cells that produce the myelin sheath that provides the insulating coating to nerves.  Additional studies showed that approximately 20—35% of patients with MS have antibodies in their blood that bind tightly to both EBNA1 and GlialCAM.

Importance of this Work for Lupus Patients
While data in the recently published article focused on the relationship between MS and EBV, this finding has important implications for all autoimmune diseases. The tools and methods used in these studies can be applied to lupus research. In fact, Dr. Robinson’s laboratory has ongoing studies related to lupus and EBV – partially supported by the LRA — since it is possible that EBV and other viruses may trigger lupus disease onset.

LRA Chief Scientific Officer Teodora Staeva said, “We are encouraged by this important discovery by Dr. Robinson and his team. Clearly identifying a cause for MS could lead to new preventive and treatment strategies. I am particularly excited about Dr. Robinson’s similar line of investigation in lupus and look forward to the outcomes of this study and their implications for individuals with lupus.”