In a new study published on April 11, investigators in Italy found that, in patients with relapsing-remitting multiple sclerosis (RRMS), the immune response to the Epstein-Barr virus (EBV) appeared to cycle simultaneously with their disease activity, meaning that when the virus was active, so was their MS.
The study, conducted by investigators at the Santa Lucia Foundation in Rome, Italy examined cytotoxic (CD8+) T-cells, which are cells that kill infected or abnormal cells in the body. They found an increased response to the antigens produced by active EBV in the blood of MS patients during relapses, as compared with samples taken during periods of remission. Antigens are substances that the body sees as foreign or harmful—including toxins from viruses like Epstein-Barr—and deploys an immune response to find and kill.
EBV is a member of the herpesvirus family and, according to the
Although the symptoms of mono, which include a fever, sore throat, and swollen lymph glands, eventually go away, EBV takes up a permanent residence in certain cells in the immune system where it lies dormant for years.
For people who suffer from RRMS, the cycles of disease activity can be as varied and irregular as the symptoms they produce. Multiple sclerosis is an autoimmune disease that affects the central nervous system, including the brain and spinal cord. The immune system attacks the myelin, or protective covering, of nerve cells in the brain, causing electrical “shorts” in the signaling pathways.
This can result in symptoms ranging from mild numbness to blindness or complete paralysis. In the relapsing-remitting form of MS, these attacks can last from a few days to several months. The flare-ups are followed by periods of remission where there is a lessening of disease activity.
More than 400,000 people have been diagnosed with MS in the United States, and more than 1.2 million worldwide. According to the Multiple Sclerosis Association of America, about 80 to 85 percent of MS patients are initially diagnosed with relapsing-remitting MS.
Tracking the Disease Cycles
In the study, investigators followed 113 patients with RRMS and 49 healthy control subjects over the course of four years, analyzing their blood in order to track their levels of CD8+ T-cell activity and map it to their MS disease cycles. Of the RRMS patients, 79 were on no disease modifying therapy, 20 were on Interferon Beta 1a, and 14 were on natalizumab, which is sold as Tysabri.
Patients experiencing a relapse of their MS, verified by magnetic resonance imaging (MRI) scans of the brain, also showed elevated EBV activity as measured by the presence of the CD8+ T-cells.
The researchers also studied the brain tissue of five MS patients who had donated their bodies to science. They found an interaction between an active EBV-specific protein and CD8+ T-cells in MS lesions in the brains of those patients at the time of their deaths.
Could There Be a Viral Trigger for MS?
The role of EBV as a potential trigger for multiple sclerosis has long been debated. Whether it—or any virus—directly causes the disease or creates a “perfect storm” situation whereby the immune system, in trying to eradicate the virus, goes haywire and mistakes myelin proteins as the enemy, is unclear.
According to Dr. Steven Jacobson, Chief of the Viral Immunology Section at the National Institute of Neurological Disorders and Stroke, it's important to note that "While EBV may be one of the triggers in MS...what triggers reactivation in one person may not in another." He told Healthline that MS is not a disease with a single, defined, viral trigger like AIDS, for example, which is triggered by the HIV virus.
“The results [of this study] do not answer the question of whether EBV dysregulation is a consequence or cause of MS," said Dr. Tom Ech, Program Officer of the Autoimmunity and Mucosal Immunology branch of the NIH in an interview with Healthline, "but suggest a link between EBV reactivation, antiviral immune response and disease activity during the relapsing-remitting stage of MS.”
The results of this study suggest that the ebb and flow of EBV as it cycles between dormant and active phases could set the stage for the reactivation of MS. This has led to the hypothesis that RRMS could be controlled with antiviral drugs that keep EBV in check. However, many more studies will be required to prove or disprove this theory.
"What this group [of researchers] has shown is that further studies need to be done with antiviral drugs," said Jacobson, who has been studying viruses and MS for more than 30 years at the NIH. "In fact, the 'interfere' part of the name 'interferon' [used to treat RRMS] stands for the drug's ability to interfere with viral replication within cells. This also raises the question of whether this classic therapy for MS could be used as an antiviral drug."
Although there is currently no vaccine for the Epstein-Barr virus, researchers are working diligently to develop one. Australian scientists at the Queensland Institute of Medical Research have conducted the first human trial of an
Although this newest study does provide a tantalizing glimpse into possible interactions between the immune system and viruses, it doesn't prove that EBV is a viral trigger for MS. It's not a "smoking gun," but rather another piece of the overall puzzle in what is a complex disease process.
Jacobson said that the US government, through the NIH, has been devoting more funding to MS research than ever before, including partially funding this study, as well as others involving therapies now on the market.
There are medication on the market now to help control MS symptoms, but the ultimate goal is to stop it in its tracks. "While we are able to suppress the disease activity [with the current therapies]," said Jacobson, "the key is to stop degeneration."