Association analysis between symptomology and herpesvirus IgG antibody concentrations in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS) are two complex and multifactorial diseases whose patients  experience persistent fatigue, cognitive impairment, among other shared symptoms.  The onset of these diseases has also been linked to acute herpesvirus infections  or their reactivations. In this work, we re-analyzed a previously-described  dataset related to IgG antibody responses to 6 herpesviruses (CMV -  cytomegalovirus; EBV - Epstein-Barr virus; HHV6 - human herpesvirus-6; HSV1 and  HSV2 - herpes simplex virus-1 and -2, respectively; VZV - varicella-zoster virus)  from the United Kingdom ME/CFS biobank. The primary goal was to report the  underlying symptomology and its association with herpesvirus IgG antibodies using  data from 4 disease-trigger-based subgroups of ME/CFS patients (n = 222) and  patients with MS (n = 46). The secondary objective was to assess whether  serological data could distinguish ME/CFS and its subgroup from MS using a  SuperLearner (SL) algorithm. There was evidence for a significant negative  association between temporary eye insight disturbance and CMV antibody  concentrations and for a significant positive association between bladder  problems and EBV antibody concentrations in the MS group. In the ME/CFS or its  subgroups, the most significant antibody-symptom association was obtained for  increasing HSV1 antibody concentration and brain fog, a finding in line with a  negative impact of HSV1 exposure on cognitive outcomes in both healthy and  disease conditions. There was also evidence for a higher number of significant  antibody-symptom associations in the MS group than in the ME/CFS group. When we  combined all the serological data in an SL algorithm, we could distinguish three  ME/CFS subgroups (unknown disease trigger, non-infection trigger, and an  infection disease trigger confirmed in the lab at the time of the event) from the  MS group. However, we could not find the same for the remaining ME/CFS group  (related to an unconfirmed infection disease). In conclusion, IgG antibody data  explains more the symptomology of MS patients than the one of ME/CFS patients.  Given the fluctuating nature of symptoms in ME/CFS patients, the clinical  implication of these findings remains to be determined with a longitudinal study.  This study is likely to ascertain the robustness of the associations during  natural disease course.