Revisiting IgG antibody reactivity to Epstein-Barr Virus in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome and its potential application to disease diagnosis

Key research findings:

• Epstein-Barr virus (EBV) infection is commonly reported at the onset of ME/CFS, but could antibodies against EBV serve as biomarkers of the disease?
• No differences in antibody responses were found between blood samples from 92 ME/CFS patients and 50 healthy control subjects.
• However, when analysing only patients with a reported infectious onset of disease, antibody responses against two EBV-related antigens were stronger in the patient group; these results need confirmation.

Research abstract:

Infections by the Epstein-Barr virus (EBV) are often at the disease onset of patients suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, serological analyses of these infections remain inconclusive when comparing patients with healthy controls (HCs). In particular, it is unclear if certain EBV-derived antigens eliciting antibody responses have a biomarker potential for disease diagnosis.

With this purpose, we re-analyzed a previously published microarray data on the IgG antibody responses against 3,054 EBV-related antigens in 92 patients with ME/CFS and 50 HCs. This re-analysis consisted of constructing different regression models for binary outcomes with the ability to classify patients and HCs. In these models, we tested for a possible interaction of different antibodies with age and gender. When analyzing the whole data set, there were no antibody responses that could distinguish patients from healthy controls.

A similar finding was obtained when comparing patients with non-infectious or unknown disease trigger with healthy controls. However, when data analysis was restricted to the comparison between HCs and patients with a putative infection at their disease onset, we could identify stronger antibody responses against two candidate antigens (EBNA4_0529 and EBNA6_0070).

Using antibody responses to these two antigens together with age and gender, the final classification model had an estimated sensitivity and specificity of 0.833 and 0.720, respectively. This reliable case-control discrimination suggested the use of the antibody levels related to these candidate viral epitopes as biomarkers for disease diagnosis in this subgroup of patients.

To confirm this finding, a follow-up study will be conducted in a separate cohort of patients.

Research authors & location:

Nuno Sepúlveda, João Malato, Franziska Sotzny, Anna D Grabowska, André Fonseca, Clara Cordeiro, Luís Graça, Przemyslaw Biecek, Uta Behrends, Josef Mautner, Francisco Westermeier, Eliana M Lacerda, Carmen Scheibenbogen in Front Med (Lausanne). 2022 Jun 24;9:921101 [doi: 10.3389/fmed.2022.921101] eCollection 2022.

ME Research UK: Revisiting IgG antibody reactivity to EBV in ME/CFS and its potential application to disease diagnosis (meresearch.org.uk)