Herpesviruses Serology Distinguishes Different Subgroups of Patients From the United Kingdom Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Biobank.
Tiago Dias Domingues, Anna D Grabowska, Ji-Sook Lee, Jose Ameijeiras-Alonso, Francisco Westermeier, Carmen Scheibenbogen, Jacqueline M Cliff, Luis Nacul, Eliana M Lacerda, Helena Mouriño, Nuno Sepúlveda
Author Information
Tiago Dias Domingues: Departamento de Estatística e Investigação Operacional, Faculdade de Ciências, Universidade de Lisboa, Lisboa, 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.
Francisco Westermeier: Institute of Biomedical Science, Department of Health Studies, FH Joanneum University of Applied Sciences, Graz, Austria.
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.
Jacqueline M Cliff: Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Luis Nacul: Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Eliana M Lacerda: Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Helena Mouriño: Departamento de Estatística e Investigação Operacional, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal.
Nuno Sepúlveda: CEAUL-Centro de Estatística e Aplicações da Universidade de Lisboa, Lisboa, Portugal.
The evidence of an association between Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and chronic herpesviruses infections remains inconclusive. Two reasons for the lack of consistent evidence are the large heterogeneity of the patients' population with different disease triggers and the use of arbitrary cutoffs for defining seropositivity. In this work we re-analyzed previously published serological data related to 7 herpesvirus antigens. Patients with ME/CFS were subdivided into four subgroups related to the disease triggers: S-42 patients who did not know their disease trigger; S-43 patients who reported a non-infection trigger; S-93 patients who reported an infection trigger, but that infection was not confirmed by a lab test; and S-48 patients who reported an infection trigger and that infection was confirmed by a lab test. In accordance with a sensitivity analysis, the data were compared to those from 99 healthy controls allowing the seropositivity cutoffs to vary within a wide range of possible values. We found a negative association between S and seropositivity to Epstein-Barr virus (VCA and EBNA1 antigens) and Varicella-Zoster virus using specific seropositivity cutoff. However, this association was not significant when controlling for multiple testing. We also found that S had a lower seroprevalence to the human cytomegalovirus when compared to healthy controls for all cutoffs used for seropositivity and after adjusting for multiple testing using the Benjamini-Hochberg procedure. However, this association did not reach statistical significance when using Benjamini-Yekutieli procedure. In summary, herpesviruses serology could distinguish subgroups of ME/CFS patients according to their disease trigger, but this finding could be eventually affected by the problem of multiple testing.
