Are ME/CFS symptoms related to levels of human herpes virus antibodies?

ME/CFS and multiple sclerosis (MS) – an autoimmune disease – share some similarities. They are both complex, multisystem diseases and have overlapping symptoms including debilitating fatigue, sensitivity to light, and cognitive dysfunction. Interestingly, the development of both diseases has also been linked to infection by herpes viruses.

Viruses, specifically human herpes viruses, and how they may be involved in the development and disease course of ME/CFS is an ongoing area of research. For example, a study funded by ME Research UK is currently investigating whether viral activity can contribute to the disease process in ME/CFS.

Another recent study, using data from the UK ME/CFS Biobank (whose creation was part funded by ME Research UK), considered whether viral activity could also be linked to the symptoms experienced by people with ME/CFS and MS, and whether there were differences in the findings between the two diseases.

What did the study do? 

The study used data from the UK ME/CFS Biobank and included 46 people with MS and 222 people with ME/CFS (diagnosed using either the 1994 CDC criteria for CFS, sometimes referred to as the Fukuda criteria, or the 2003 Canadian Consensus Criteria for ME/CFS). 

Those with ME/CFS were divided into four subgroups based on what the participants reported was the trigger for their illness:

  1. Unknown trigger  (42 people),
  2. Non-infectious trigger (42 people),
  3. An infection that was not confirmed by a lab test at the time of the event (96 people), or
  4. An infection confirmed by lab test at the time of the event (46 people).

The researchers collated information on the concentration of antibodies produced in response to a herpes virus infection in blood samples from the participants.

They then considered whether there was an association between the herpesvirus antibodies, and the presence or absence of the number of symptoms experienced over the last 7 days relating to post-exertional malaise, sleep function, the immune system, interactions between nerves and hormones (neuroendocrine system), cognition, and pain.

This was done both overall for people with ME/CFS, and in each of the disease trigger subgroups. The results were compared with those for people with MS.

What were the key findings?

Differences in symptoms 

People with ME/CFS reported that they had experienced a higher total number of symptoms over the last 7 days compared with people with MS. Those with ME/CFS also reported experiencing symptoms more frequently than those with MS. The most common symptom experienced by people with ME/CFS, both overall and in each of the four disease trigger groups, was post-exertional malaise lasting more than 24 hours.

The two ME/CFS infectious trigger subgroups (confirmed, or unconfirmed by a lab test) had a symptom profile most similar to that of people with MS. Interestingly, these two ME/CFS subgroups were composed mostly of people with mild to moderate ME/CFS.

Associations between symptoms and antibodies 

Certain symptoms were found to be associated with antibodies for herpesviruses. For each of the disease groups, these were:

ME/CFS overall: brain fog, chest and abdominal pain

ME/CFS subgroups: 

  1. Unknown trigger: neck weakness, fever or chills;
  2. Non-infectious trigger: difficulty retaining information;
  3. Infection not confirmed by a lab test: short term memory problems and post exertional malaise; and
  4. Infection confirmed by lab test: light-headedness and bladder problems.

MS: eyesight disturbances, bladder problems, difficulty understanding and negative impact of stress.

Antibodies may differentiate some ME/CFS subgroups

Complex analysis suggested that three ME/CFS subgroups – unknown disease trigger, non-infectious trigger, and a confirmed infectious trigger – could be distinguished from the MS group. However, the subgroup whose trigger was an unconfirmed infection could not.


This study found that while herpesvirus antibodies were associated with some symptoms in both people with ME/CFS and MS, there were more antibody-symptom associations for people with MS overall. The results also showed that the antibody-symptom associations identified could not be used to differentiate all people with ME/CFS from those with MS – this differentiation is important because it is something that would be required for a biomarker for ME/CFS.

The authors acknowledge some limitations of the study, and note that while antibodies to particular viruses are a marker of a past active infection, they are unable to provide information on when the infection occurred, or indeed if the virus is currently active or not. This means that the researchers were not able to distinguish whether the herpesvirus infection happened before or after the onset of ME/CFS or MS.

In addition, this was a cross-sectional study, which only provides information regarding a particular snapshot in time. Given the fluctuating nature of symptoms in ME/CFS, future research is needed using a study design that follows participants up over time, taking repeat measurements of information.

Another limitation of this research is that it considers people with ME/CFS diagnosed using two different criteria – the Fukuda criteria, and the Canadian Consensus Criteria – together. These two criteria have different symptom requirements for a diagnosis, and this may have an impact on the results observed in this study. Future research should consider people diagnosed with ME/CFS using different criteria separately, or, where the number of participants allows, consider how the results differ by diagnostic criteria used.

Takeaway messages

  • People with ME/CFS experienced more symptoms, more often than those diagnosed with MS.
  • Associations were observed between antibodies to herpesvirus and symptoms in people with ME/CFS and in those with MS.
  • The exact symptoms with the strongest associations with antibodies differed between people with ME/CFS and those with MS.
  • Despite the differences, these antibody-symptom associations could not be used to accurately distinguish all people with ME/CFS from those with MS.
  • More research is needed which captures the fluctuating nature of symptoms in ME/CFS.
Verified by MonsterInsights