Epstein-Barr Virus (EBV) and Lupus

This article examines the relationship between the Epstein-Barr virus (EBV) and the development of lupus.

 

Introduction

Epstein-Barr virus (EBV) is a relatively common virus that affects individuals all over the world. EBV is a member of the herpes family of viruses and is also known as human herpesvirus 4 (HHV4).  EBV is usually passed through saliva, and while some may never experience any symptoms, others may eventually become ill and develop what is commonly known as mononucleosis (or “mono”).  There have been many studies showing a connection between lupus and EBV infections though the mechanism is not well understood.  There are some aspects of this connection that would be helpful to know.

Who is at risk, and what causes EBV?

Anyone can be at risk for becoming infected with EBV. For many, it may lay dormant without expressing symptoms. James Steckelberg, M.D. of the Mayo Clinic writes, “most EBV infections aren’t noticeable, even when they’re most active in your body. By age 35, most everyone has antibodies to EBV, including past infection.” For others with compromised immune systems, however, symptoms may develop and the individual may become very sick as though having a lingering cold or flu virus.

According to the Centers for Disease Control and Prevention (CDC), the easiest way to spread the virus is through:

  • Kissing (the reason mono is often referred to as the “kissing” disease).
  • Sharing drinks, straws and cups, or sharing food and using the same utensils.
  • Using the same toothbrush.
  • Playing with toys an infected child has drooled on.

The disease can also spread through other bodily fluids, however, such as blood, semen and even during organ transplants.

What are the Symptoms of EBV?

According to the CDC, when a normally healthy child contracts EBV, they usually do not show any symptoms other than maybe being mildly sick. When a teenager or adult contracts EBV, however, they may experience more severe symptoms including:

  • Feeling tired, run-down and extremely fatigued.
  • Fevers, aches and chills.
  • A sore, inflamed throat.
  • Swollen glands or lymph nodes in the neck.
  • Liver swelling.
  • Rashes and hives.

The time form the initial infection to the time that these symptoms first appear is called the incubation period and that can take 4 to 6 weeks.  For individuals diagnosed with EBV, the duration of the symptoms can be highly variable, though they usually start feeling better within two to four weeks.  This depends upon the intensity of symptoms and any other health conditions they might have. It is important to note that an individual may be infectious – able to pass the virus on to someone else via their saliva – for several weeks or even months after they stop feeling sick themselves.

As someone who has had mono twice (early in my teens and then again in my early 20’s), I can attest to experiencing each and every one of the above symptoms. At first, it felt like a nagging cold that would not go away.  I kept pushing through it until I developed a chronic sore throat, laryngitis and exhaustion. In hindsight, I realized I had been sick for over a month. I finally went to my healthcare practitioner and tested positive for mono. I was told to rest and limit my activities for four weeks, but I remember feeling tired and lethargic for months, which can be common.

How is EBV diagnosed and treated?

According to the CDC, EBV can be diagnosed during a visit with a healthcare practitioner. It may be challenging to diagnose at first because EBV mimics other viral illnesses. It is important to follow up with a healthcare practitioner if your symptoms do not go away after a couple of weeks. A simple blood test can check for the antibodies that are present with EBV.

EBV can be treated much like the common cold or flu. The CDC suggests getting plenty of rest and drinking plenty of fluids if an individual has active EBV. Over-the-counter medicines such as fever reducers and pain relievers often help. According to research finding at Johns Hopkins, symptoms usually last around three to four weeks and individuals are often told to limit their activity. In more severe cases, prednisone may be prescribed to treat symptoms such as the pain and inflammation of an unrelenting sore and swollen throat.

What is the relationship between EBV and lupus?

Researchers have noted that while 99.5% of adults with SLE are infected with EBV, so is approximately 95% of the healthy population.  So, EBV infections are not always a specific cause.  The correlation between EBV and SLE is more significant, however, when looking at children. Of healthy children studied, 70% were found to be infected with EBV.  However, 99.6% of children with SLE are infected. Since healthy children are not old enough to have built up the EBV antibody levels of an adult, it stands to reason that there may indeed be a relation between EBV and autoimmune disease and a strong argument for more research.

This research goes on to explain how SLE and “EBV-induced IM (infectious mononucleosis) are known to have similar symptoms and clinical manifestations, indicating an association.” The researchers noted that there is a “presence of rheumofactor and antibodies against cellular components like DNA, histones, and ribonucleoproteins” in both individuals with SLE and EBV-induced IM. An article published in the July 2012 issue of the journal Current Opinion in Rheumatology supports these finding, suggesting that how EBV manifests may influence who develops SLE and how SLE develops. Both articles suggest the roles cytotoxic T cells – the T cells that kill virally infected cells – and plasmacytoid dendritic cells – cells with antigen-presenting potential – may play in the relationship between the expression of EBV and SLE.

In 2018, researchers further explored how the presence of EBV may change how our immune system behaves. According to Cincinnati Children’s Hospital, when an individual gets a viral or bacterial infection, the B cells found in our bodies create an abundance of antibodies to defend itself from the illness and make us well. When an individual contracts EBV, however, EBV itself takes over an individual’s B cells and “re-programs” them in order to take control, negatively impacting health.

In a 2018 study conducted by Cincinnati Children’s Hospital, experts discovered that EBV takes control of B cells by using tiny proteins or “transcription factors.” Transcription factors are already present on human genomes and affect how specific cells behave. When EBV “re-writes” transcription factors, however, B cells do not behave as expected, putting individuals at risk for developing several other diseases in addition to mono including:

What made this study possible now rather than 10 years ago is technology – the “genomic methods” that were not available in the early part of this century have been developed paving the way for greater opportunities for research. Researchers of this study found a protein that is produced by EBV – EBNA2 – that binds to the same genomes that are associated with the diseases listed above. What researchers have found is that when there are clusters of EBNA2 proteins present in an individual’s genome, there is a greater risk for that individual to develop lupus.

Cincinnati Children’s Hospital’s researchers are hoping that these promising discoveries encourage experts who study other diseases to come together to support each other and further advance research.

In Conclusion

Though not one of the classic overlap disease, EBV may play a significant role in lupus and SLE. If you are an individual with lupus, you more than likely have been infected with and experienced symptoms of EBV. As researchers and healthcare professionals learn more and more about these health conditions and how they may be related, they will also be able to develop safer, more effective treatments for keeping individuals with autoimmune diseases such as lupus healthy.

References

About Epstein-Barr virus (EBV). (2018). Retrieved from: https://www.cdc.gov/epstein-barr/about-ebv.html

Auwaerter, P. (2019). Epstein-Barr virus. Retrieved from: https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540208/all/Epstein_Barr_Virus#3

Draborg, A., Duus, K., & Houen, G. (2012). Epstein-Barr virus and systemic lupus erythematosus. Clinical and Developmental Immunology. Retrieved from: http://downloads.hindawi.com/journals/jir/2012/370516.pdf

Harley, J., Chen, X., Pujato, M., Miller, D., Maddox, A., Forney, C., …Weirauch, M. (2018). Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity. Nature Genetics. 50(5) 699-707. Retrieved from:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022759/pdf/nihms939557.pdf

James, J.A., Neas, B. R., & Moser, K.L.  (2001). Systemic lupus erythematosus in adults is associated with previous Epstein- Barr virus exposure. Arthritis and Rheumatism, 44(5), 1122–1126.

James, J. & Robertson, J. (2012). Lupus and Epstein-Barr. Current Opinions in Rheumatology. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562348/pdf/nihms436498.pdf

Mono virus linked to seven serious diseases. (2018). Retrieved from: https://www.cincinnatichildrens.org/news/release/2018/mono-virus

Steckelberg, J. (n.d.). Mononucleosis and Epstein-Barr: What’s the connection? Retrieved from: https://www.mayoclinic.org/diseases-conditions/mononucleosis/expert-answers/mononucleosis/faq-20058444

Author: Liz Heintz

Liz Heintz is a technical and creative writer who received her BA in Communications, Advocacy, and Relational Communications from Marylhurst University in Lake Oswego, Oregon. She most recently worked for several years in the healthcare industry. A native of San Francisco, California, Liz now calls the beautiful Pacific Northwest home.

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