Analysing antibody responses against EBV-derived antigens in ME/CFS

Principal investigators

Dr Nuno Sepúlveda & Prof. Carmen Scheibenbogen


London School of Hygiene & Tropical Medicine and Charité Universitätmedizin Berlin

Start date

October 2020


This project is funded by ME Research UK with the financial support of The Fred and Joan Davies Bequest.

Background and aim

Dr Nuno Sepúlveda

The emergence of so-called ‘long COVID’ has highlighted the potential long-term health consequences of infection with a virus like SARS-CoV-2, leading to symptoms such as fatigue, muscle pain and brain fog that may last for weeks or months.

Of course, this is a familiar scenario to many people with ME/CFS whose illness started shortly after being infected with a virus. Not to mention the similarities in symptoms between ME/CFS and long COVID.

So it is no surprise that significant biomedical research into the causes of ME/CFS over the years has focused on the role of viral infection as a trigger for the illness. In particular, specific viruses such as Epstein-Barr virus (EBV) and human endogenous retroviruses (HERVs) have attracted special attention.

While HERVs are currently being investigated by Prof. Oltra in Valencia, the involvement of EBV in ME/CFS forms the basis of another study awarded funding by ME Research UK.

Dr Nuno Sepulveda at the London School of Hygiene & Tropical Medicine in collaboration with Prof. Carmen Scheibenbogen at Charité Universitätmedizin Berlin are investigating responses to EBV as a possible biomarker for ME/CFS.

Nearly all people are infected with EBV at some time in their lives, and in most cases the immune system efficiently takes care of the virus. This leaves the individual with adaptive immunity – antibodies that can recognise and eliminate future EBV infections.

However, EBV can cause glandular fever in children and young adults, and has been associated with the development of a number of autoimmune conditions such as lupus, rheumatoid arthritis and multiple sclerosis (i.e. diseases caused by an abnormal immune response).

EBV has also long been suggested as a trigger for ME/CFS, and Dr Sepulveda highlights four main reasons for this:

  1. Most humans are chronically infected with EBV.
  2. The virus is already known to cause several diseases, including autoimmune conditions.
  3. It produces proteins similar to ones that are found in the body.
  4. People with ME/CFS are often found to have active EBV infections or antibody reactivity against EBV.

In previous experiments, Prof. Scheibenbogen and her team found that antibody responses against two EBV-derived proteins (antigens) in particular were increased in people with ME/CFS compared with healthy control subjects. These two antigens are similar to the human proteins lactoperoxidase and thyroid peroxidase

Dr Sepulveda’s group then took that data and analysed it further to identify more antigens that were increased or decreased in ME/CFS patients compared with control subjects.

The results were used to develop a statistical model that could predict a diagnosis of ME/CFS based on the antibody responses to those antigens. The model was particularly sensitive in identifying ME/CFS patients with an infectious trigger for their illness.

The investigators believe these findings are a very promising stage in the search for biomarkers for ME/CFS, so it is very important to test whether they can be confirmed in other groups of patients.

The aim of their new study is therefore to do just that – to evaluate the top fifteen EBV-derived antibody responses in samples from 100 people with ME/CFS, 50 healthy control subjects and 50 patients with multiple sclerosis, all obtained from the UK ME/CFS Biobank.

If the initial findings are confirmed, and these responses can be used as disease-specific biomarkers able to discriminate people with ME/CFS, that would be a huge and much-needed step forward in the diagnosis of this illness.

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