Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients (2019) Blomberg et al

wigglethemouse

Senior Member (Voting Rights)
Another look to see if the immune antibody signature to Human Herpes virus's in patients is different to controls.
https://www.frontiersin.org/articles/10.3389/fimmu.2019.01946/full
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.
 
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If I understood correctly it's not about exposure to herpesviruses cause these are ubiquitous and IgG did not differ between patients and controls.

If these viruses do play a role in ME/CFS, as some EBV-studies suggest, it is probably because the immune system of some ME/CFS patients respond differently to herpesviruses.

The authors of this study think that the minor differences they have found in antibody reactivities in ME/CFS samples versus controls with whole virus HHV-1 antigens and recombinant EBV EBNA6 and EA antigens form an indication for this.
 
People that die from oncogenic viral brain tumors do not have any evidence of serological antibodies to their giant brain tumors that make them die.

HHV exists in lymphatics for transmission purposes at best. So do a biopsy of the lymph nodes or a lumbar puncture (you will not get very robust results) but for sure do not this.
 
Drumroll please: presenting a paper that does not start with a version of "ME is a fatiguing condition":
Myalgic encephalomyelitis, also referred to as chronic fatigue syndrome (ME/CFS), is a common syndrome which includes post-exertional malaise (PEM), brain fog, unrefreshing sleep, hemodynamic abnormality, myalgia, and headache.
Can anybody explain what 'degree of reactivity' means?
As seen in Figure 1, the degree of HHV-1 reactivity of ME/CFS and FM patients were lower than those of blood donor controls. In contrast, the HHV-2 antigen reacted equally in the three categories. However, when the degree of reactivity (MFI) for ME/CFS and BD samples were compared using the Mann-Whitney U test, neither HHV-1, and HHV-2 antigens showed significant differences (p > 0.05).
 
Commentary: Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients
Studies to ascertain a possible relationship between herpesviruses and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have relied heavily on classical approaches, specifically, serological examination for antibodies against virus proteins, primarily structural, and/or increases in viral load (121). These data have been conflicting due in part to several features: the heterogeneity of the disease, high prevalence of the herpesviruses in the population since they can establish lifelong infections, and differences between laboratories.

Two additional problems lead to conflicting data in serological studies: which viral antigens are to be used for detection, and what is the possible relationship, if any, of these viral antigens to ME/CFS? These are important questions that must be addressed for any data to provide meaningful insight into the possible contribution of a virus to the pathophysiology of ME/CFS. Although the experimental techniques used in Blomberg's serological study were appropriate, the selection of specific herpesviruses and viral antigens studied gives a limited view of the humoral response in ME/CFS.
Open access, https://www.frontiersin.org/articles/10.3389/fimmu.2020.01400/full
 
Commentary: Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Open access, https://www.frontiersin.org/articles/10.3389/fimmu.2020.01400/full
The author Maria Ariza has published several papers with Marshall Williams and it looks like they are part of the same team looking at EBV. This is her profile
https://loop.frontiersin.org/people/170539/publications

For background Marshall Williams has a long standing ME/CFS grant which was renewed for another 5 years this year (year 11 of grant, year 6 for ME/CFS I believe).
https://projectreporter.nih.gov/project_info_description.cfm?aid=10049715&icde=31258613
 
I think this is the meat and potatoes regarding Herpes Viruses and ME/CFS that the author is trying to get across
If a causal relationship is to be established between EBV, HHV-6, or any other herpesvirus and ME/CFS, it will require addressing the role of viral proteins produced during abortive-lytic replication of the herpesviruses, which does not lead to new viral progeny, and thus, no changes in viral load would be observed.

Therefore, measuring humoral responses in patients' sera using virus lysate is not appropriate because it would only detect antibodies to proteins that are components of the virion but not to proteins expressed during abortive-lytic replication.
 
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