Herpesviruses Serology Distinguishes Different Subgroups of Patients From the United Kingdom Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Biobank.

Abstract

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(0)-42 patients who did not know their disease trigger; S(1)-43 patients who  reported a non-infection trigger; S(2)-93 patients who reported an infection  trigger, but that infection was not confirmed by a lab test; and S(3)-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(1) 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(3) 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.