Analysing Antibody Responses against EBV-derived Antigens in ME/CFS

Project description

In previous experiments, Prof. Scheibenbogen and her team found that antibody responses against two Epstein-Barr-Virus (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.

In previous experiments – using data from Prof. Carmen Scheibenbogen’s group at Charité Universitätmedizin Berlin – Dr Sepúlveda identified a number of EBV-derived proteins (antigens) that were increased or decreased in ME/CFS patients compared with control subjects.

Dr Sepúlveda has now extended this work by looking specifically for antibody signatures that could serve as biomarkers for ME/CFS, and focussing on patients with an infectious trigger at their disease onset. The research was conducted in collaboration with a number of other researchers, including Prof. Scheibenbogen in Berlin, and Dr Eliana Lacerda at the London School of Hygiene & Tropical Medicine. The group analysed antibody responses against 3,054 EBV-derived antigens in 92 patients with ME/CFS and in 50 healthy control subjects. Fifty-four of the patients reported an acute infection at the time their disease began. The first round of analyses did not find any antibodies associated with ME/CFS, but this changed when the patients were divided into subgroups based on their disease onset. While there were still no associations among those with a non-infectious or unknown disease trigger, in ME/CFS patients with an infection at disease onset two antibody responses were stronger than seen in healthy controls.

Further analyses showed that these two responses could distinguish this subgroup from controls with a high sensitivity and specificity, and may therefore have potential in the diagnosis of these ME/CFS patients with an infectious trigger, specifically those affected by EBV. Importantly, the researchers plan to confirm these findings in other cohorts of patients from the UK ME/CFS Biobank. They also suggest that the specific EBV-derived antigens identified may provide some evidence of how the reactivation of EBV plays a role in the development of ME/CFS.

(Description adapted from project websites: see link above)