HHV-6 AND AUTOANTIBODIES TO MUSCARINIC ACETYLCHOLINE RECEPTORS AS POTENTIAL BIOMARKERS IN THE DIAGNOSTIC ALGORITHM OF MYALGIC ENCEPHALOMYELITIS/CHRONIC FATIGUE SYNDROME

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 analyse the association between ME/CFS clinical course severity, presence of HHV-6A/B infection markers, and plasma levels of autoantibodies against muscarinic acetylcholine receptors. A total of 134 patients with ME/CFS and 33 healthy controls were analysed for the presence of HHV-6A/B using PCRs, and antibodies against 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, in 18/73 with moderate, and in 7/30 with mild ME/CFS clinical course. Severity-related differences were found among
those with the HHV-6 load of more than 1,000 copies/106 PBMCs. 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 disease severity did not show any difference; however, increased viral load correlated with the increase in
anti-M4 level. ME/CFS patients with high HHV-6 load had 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 levels was 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 correlated with the increase in anti-M4 level. Elevated levels of antibodies against M4 receptors in ME/CFS patients support their usage as clinical biomarkers in the diagnostic algorithm of ME/CFS.