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Association analysis between symptomology and herpesvirus IgG antibody concentrations in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis
Authors
J Ameijeiras-Alonso
P Biecek
+11 more
JM Cliff
AD Grabowska
L Graça
E Lacerda
J-S Lee
J Malato
H Mouriño
L Nacul
C Scheibenbogen
N Sepúlveda
F Westermeier
Publication date
13 July 2023
Publisher
Elsevier (Cell Press)
Doi
Abstract
Data availability statement: The data set used in this study is freely available from the United Kingdom ME/CFS biobank upon application.Supplementary data are available online at https://www.sciencedirect.com/science/article/pii/S2405844023054580?via%3Dihub#appsec2 .Copyright © 2023 The Authors. 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.This research was funded by: FCT - Fundação para a Ciência e Tecnologia, Portugal, ref. grant: SFRH/BD/149758/2019 (J.M.), and UIDB/00006/2020 (T.D.D., J.M., H.M., NS); the Polish National Agency for Academic Exchange (NAWA), ref. grant: PPN/ULM/2020/1/00069/U/00001 (N.S.). The UKMEB was established with a joint grant from the charities ME Association (including continuing support), ME Research UK and Action for ME, as well as private donors. Research reported in this manuscript was supported by the National Institutes of Health (NIH) under award number 2R01AI103629
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Last time updated on 14/09/2023