Association analysis between symptomology and herpesvirus IgG antibody concentrations in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis
Tiago Dias Domingues,
João Malato,
Anna D. Grabowska,
Ji-Sook Lee,
Jose Ameijeiras-Alonso,
Przemysław Biecek,
Luís Graça,
Helena Mouriño,
Carmen Scheibenbogen,
Francisco Westermeier,
Luis Nacul,
Jacqueline M. Cliff,
Eliana Lacerda,
Nuno Sepúlveda
Affiliations
Tiago Dias Domingues
Departamento de Estatística e Investigação Operacional, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal; Faculty of Mathematics & Information Science, Warsaw University of Technology, Warsaw, Poland
João Malato
Faculty of Mathematics & Information Science, Warsaw University of Technology, Warsaw, Poland; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
Anna D. Grabowska
Department of Biophysics, Physiology, And Pathophysiology, Medical University of Warsaw, Warsaw, Poland
Ji-Sook Lee
Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
Jose Ameijeiras-Alonso
Department of Statistics, Mathematical Analysis and Optimization, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Przemysław Biecek
Faculty of Mathematics & Information Science, Warsaw University of Technology, Warsaw, Poland
Luís Graça
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
Helena Mouriño
Departamento de Estatística e Investigação Operacional, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal; Faculty of Mathematics & Information Science, Warsaw University of Technology, Warsaw, Poland
Carmen Scheibenbogen
Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
Francisco Westermeier
Department of Health Studies, Institute of Biomedical Science, FH Joanneum University of Applied Sciences, Graz, Austria; Centro Integrativo de Biología y Química Aplicada (CIBQA), Universidad Bernardo O'Higgins, Santiago, Chile
Luis Nacul
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; BC Women’s Hospital, Vancouver, BC V6H 3N1, Canada
Jacqueline M. Cliff
Department of Life Sciences and Centre for Inflammation Research and Translational Medicine, Brunel University London, United Kingdom
Eliana Lacerda
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
Nuno Sepúlveda
Faculty of Mathematics & Information Science, Warsaw University of Technology, Warsaw, Poland; Faculty of Mathematics & Information Science, Warsaw University of Technology, Warsaw, Poland; Corresponding author. Faculty of Mathematics & Information Science, Warsaw University of Technology, Warsaw, Poland
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.
