Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease where the immune system attacks healthy tissues and organs, causing widespread inflammation affecting skin, joints, kidneys, heart, lungs, and brain, with symptoms like fatigue, fever, rashes (especially a butterfly-shaped facial rash), joint pain, and mouth sores that vary in severity and occur in flares and remissions, triggered by genetic and environmental factors. The cause of the disease remains obscure.
A report from the Division of Immunology and Rheumatology at Stanford University School of Medicine suggests that the Epstein-Barr virus (EBV) – the virus that causes mononucleosis – may be a direct cause of SLE. The paper, published in Science Translational Medicine, and the school’s press release regarding it are available for download below. The report is very technical and beyond the ken of anyone not up to date on the latest analytic methods of molecular biology. I’ll do my best to present its findings in an intelligible way. Though, as an aside, the paper is written as if unintelligiability was a primary goal. For example, I can’t find how many SLE patients and controls were studied; though a press report (not from Stanford) says that 11 lupus patients and 10 healthy controls were studied.
The EBV is well known as the cause of infectious mononucleosis. It is transmitted via saliva. Once acquired it typically remains dormant and causes no further problem. About 95% of the population has the sleeping virus in their B cells. EBV has long been thought to play a role in the pathogenesis of SLE, though no direct proof of this linkage has been found.
T cells and B cells are the primary white blood cells (lymphocytes) responsible for the adaptive immune response, which provides specific and long-lasting protection against pathogens. While both originate in the bone marrow, they mature in different locations and perform distinct functions to defend the body.
In this study, the investigators examined the B cells of healthy controls and patients with SLE. The following is taken from the Editor’s Summary provided on the journal’s website as an effort to translate the report into English:
The authors found, using a new strategy to identify EBV-infected cells by RNA sequencing, that infected B cells were transcriptionally distinct from their uninfected counterparts. EBV-infected B cells exhibited features associated with antigen presentation, and this programming seemed likely to be directly driven by the EBV protein EBNA2. These EBV-infected B cells with antigen-presenting abilities had the capacity to activate autoreactive helper T cells, setting off a chain reaction where those T cells could activate other autoreactive B cells, including uninfected ones. In vitro studies in B cell lines provided functional support for this hypothesis. These data suggest that EBV infects and reprograms autoreactive B cells that, in turn, drive the systemic autoimmune response in SLE.
Apparently, in healthy people, fewer than 1 in 10,000 B cells contain the dormant EBV. In lupus patients, this number increases to about 1 in 400. The study’s findings, obviously, need confirmation by other labs. If confirmed, not only would a role for the EBV in SLE be highly likely, but other immune diseases might be linked to the EBV.
It’s too early to implement a therapeutic plan against the virus. A vaccine would be problematic as the virus is acquired so early in life. To be effective, it would have to be given at the moment of birth. Why the virus manifests itself many years later as infectious mononucleosis is obscure. Anti-viral drug therapy might be effective if it could reach the affected B cells. The role of EBV in so called auto-immune diseases should become clear in the next few years. If EBV is the cause they are not auto-immune.
