title: Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology.
abstract: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) are debilitating diseases with overlapping symptomology and there are currently no validated tests for definitive diagnosis of either syndrome. While there is evidence supporting the premise that some herpesviruses may act as possible triggers of ME/CFS, the involvement of herpesviruses in the pathophysiology of GWI has not been studied in spite of a higher prevalence of ME/CFS in these patients. We have previously demonstrated that the deoxyuridine triphosphate nucleotidohydrolases (dUTPase) encoded by Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), and varicella-zoster virus (VZV) possess novel functions in innate and adaptive immunity. The results of this study demonstrate that a significant percentage of patients with ME/CFS (30.91-52.7%) and GWI (29.34%) are simultaneously producing antibodies against multiple human herpesviruses-encoded dUTPases and/or the human dUTPase when compared to controls (17.21%). GWI patients exhibited significantly higher levels of antibodies to the HHV-6 and human dUTPases than controls (P = 0.0053 and P = 0.0036, respectively), while the ME/CFS cohort had higher anti-EBV-dUTPase antibodies than in both GWI patients (P = 0.0008) and controls (P < 0.0001) as well as significantly higher anti-human dUTPase antibodies than in controls (P = 0.0241). These results suggest that screening of patients' sera for the presence of various combinations of anti-dUTPase antibodies could be used as potential biomarkers to help identify/distinguish patients with these syndromes and better direct treatment.
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio.
authors.forename: Peter
authors.initials: P
authors.lastname: Halpin
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio.|Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio.
authors.forename: Marshall Vance
authors.initials: MV
authors.lastname: Williams
authors.affiliation: NOVA Southeastern University, Institute for Neuro Immune Medicine, Fort Lauderdale, Florida.|Miami VA Medical Center, Miami, Florida.
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Klimas
authors.affiliation: NOVA Southeastern University, Institute for Neuro Immune Medicine, Fort Lauderdale, Florida.|Miami VA Medical Center, Miami, Florida.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Fletcher
authors.affiliation: NOVA Southeastern University, Institute for Neuro Immune Medicine, Fort Lauderdale, Florida.|University of Miami, Miami, Florida.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Barnes
authors.affiliation: Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio.|Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio.
authors.forename: Maria Eugenia
authors.identifier: 0000-0003-2560-5367
authors.initials: ME
authors.lastname: Ariza
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D001323:Autoantibodies / Q000097:blood*; D015331:Cohort Studies; D003937:Diagnosis, Differential; D015673:Fatigue Syndrome, Chronic / Q000175:diagnosis* / Q000276:immunology; D005260:Female; D004854:Herpesvirus 4, Human / Q000201:enzymology* / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018923:Persian Gulf Syndrome / Q000175:diagnosis* / Q000276:immunology; D011755:Pyrophosphatases / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase
keywords: Epstein-Barr virus; antibodies; chronic fatigue syndrome; deoxyuridine triphosphate nucleotidohydrolase; human herpesvirus 6; varicella-zoster virus