New York Native's reporting on HHV-6 is being vindicated big time. What is being ignored here, of course, is the role of HHV-6 in AIDS. We all know what that is about.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease that is mainly diagnosed based on its clinical symptoms. Biomarkers that could facilitate the diagnosis of ME/CFS are not yet available; therefore, reliable and clinically useful disease indicators are of high importance. The aim of this work was to analyze the association between ME/CFS clinical course severity, presence of HHV-6A/B infection markers, and plasma levels of autoantibodies against adrenergic and muscarinic acetylcholine receptors. A total of 134 patients with ME/CFS and 33 healthy controls were analyzed for the presence of HHV-6A/B using PCRs, and antibodies against beta2-adrenergic receptors (β2AdR) and muscarinic acetylcholine receptors (M3 AChR and M4 AChR) using ELISAs. HHV-6A/B U3 genomic sequence in whole-blood DNA was detected in 19/31 patients with severe ME/CFS, in 18/73 moderate ME/CFS cases, and in 7/30 mild ME/CFS cases. Severity-related differences were found among those with a virus load of more than 1,000 copies/106 PBMCs. Although no disease severity-related differences in anti-β2AdR levels were observed in ME/CFS patients, the median concentration of these antibodies in plasma samples of ME/CFS patients was 1.4 ng/ml, while in healthy controls, it was 0.81 ng/ml, with a statistically significant increased level in those with ME/CFS (p = 0.0103). A significant difference of antibodies against M4 AChR median concentration was found between ME/CFS patients (8.15 ng/ml) and healthy controls (6.45 ng/ml) (p = 0.0250). The levels of anti-M4 plotted against diseaseseverity did not show any difference; however, increased viral load correlates with the increase in anti-M4 level. ME/CFS patients with high HHV-6 load have a more severe course of the disease, thus confirming that the severity of the disease depends on the viral load—the course of the disease is more severe with a higher viral load. An increase in anti-M4 AchR and anti-β2AdR levels is detected in all ME/CFS patient groups in comparison to the control group not depending on ME/CFS clinical course severity. However, the increase in HHV-6 load correlates with the increase in anti-M4 level, and the increase in anti-M4 level, in turn, is associated with the increase in anti-β2AdR level. Elevated levels of antibodies against β2AdR and M4 receptors in ME/CFS patients support their usage as clinical biomarkers in the diagnostic algorithm of ME/CFS.
With an estimated prevalence of 0.1%–2.2%, ME/CFS is a multisystem disease with not yet established etiology. Patients suffer from persistent exhaustion, cognitive impairment, autonomic dysfunction, chronic pain, and flu-like symptoms, leading to a substantial reduction of life quality (18). Clinical heterogeneity in disease onset (infection versus non-infection triggered), the presence of immune-associated symptoms, and divergent immunological alterations point to the existence of subgroups of ME/CFS patients with possibly different pathomechanisms. Therefore, it is important to identify clinically useful diagnostic markers to stratify the patients into subgroups to ensure the selection of more appropriate treatment for each subgroup.
HHV-6 has long been considered as one of the ME/CFS trigger factors, and recent published data indicate that HHV6-B is associated with ME/CFS disease severity (
19). The high HHV-6 load, as well as infection in active phase, has been described in patients with fibromyalgia as well (
20). According to literature sources, HHV-6 A/B may persist in many cells and tissues long after it has disappeared from the circulation and therefore herpes viruses have been repeatedly hypothesized to underlie the chronic relapsing/remitting form of ME/CFS due to their persistence in a latent form with periodic reactivation. There are data that show that HHV-6 reactivation causes symptoms of ME/CFS such as fatigue and cognitive and autonomic dysfunction (
21). Our study shows that HHV-6 persistent infection is more frequently detected among patients with severe ME/CFS than those with a mild disease course