Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients


Jonas Blomberg, Muhammad Rizwan, Agnes Böhlin-Wiener, Amal Elfaitouri, Per Julin, Olof Zachrisson, Anders Rosén and Carl-Gerhard Gottfries


Section of Clinical Microbiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden


Myalgic encephalomyelitis, also referred to as chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by myalgia and a sometimes severe limitation of physical activity and cognition. It is exacerbated by physical and mental activity. Its cause is unknown, but frequently starts with an infection. The eliciting infection (commonly infectious mononucleosis or an upper respiratory infection) can be more or less well diagnosed. Among the human herpesviruses (HHV-1-8), HHV-4 (Epstein-Barr virus; EBV), HHV-6 (including HHV-6A and HHV-6B), and HHV-7, have been implicated in the pathogenesis of ME/CFS. It was therefore logical to search for serological evidence of past herpesvirus infection/reactivation in several cohorts of ME/CFS patients (all diagnosed using the Canada criteria). Control samples were from Swedish blood donors. We used whole purified virus, recombinant proteins, and synthetic peptides as antigens in a suspension multiplex immunoassay (SMIA) for immunoglobulin G (IgG). The study on herpesviral peptides based on antigenicity with human sera yielded novel epitope information. Overall, IgG anti-herpes-viral reactivities of ME/CFS patients and controls did not show significant differences. However, the high precision and internally controlled format allowed us to observe minor relative differences between antibody reactivities of some herpesviral antigens in ME/CFS versus controls. ME/CFS samples reacted somewhat differently from controls with whole virus HHV-1 antigens and recombinant EBV EBNA6 and EA antigens. We conclude that ME/CFS samples had similar levels of IgG reactivity as blood donor samples with HHV-1-7 antigens. The subtle serological differences should not be over-interpreted, but they may indicate that the immune system of some ME/CFS patients interact with the ubiquitous herpesviruses in a way different from that of healthy controls.


Blomberg et al., Frontiers in Immunology, 2019 August 14; 10:1946


This research was funded by the Olle Engkvist foundation, The Swedish ME Association, ME Research UK, Solve ME/CFS, The Swedish Cancer Society and Open Medicine Foundation.

Comment by ME Research UK

Published recently in Frontiers in Immunology is a new study – funded partly by ME Research UK – from the late Prof. Jonas Blomberg in Sweden. The researchers looked for evidence of past infection with, or reactivation of, the human herpesviruses HHV-4 (also known as Epstein–Barr virus), HHV-6 and HHV-7, which have been implicated in the pathogenesis of ME/CFS. Immunoglobulin G reactivity levels to these viruses were similar in serum samples from patients and control subjects, indicating that none of these herpesviruses are more common or intense in ME/CFS patients than in the rest of the population. However, the researchers did find subtle differences in antibody reactivities to whole virus HHV-1 antigens and some recombinant HHV-4 antigens in ME/CFS samples, suggesting that the immune system of patients may interact with these viruses in an abnormal way.

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