Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and deoxyribonucleotide polymerase in a chronic fatigue syndrome subset

PLoS One. 2012;7(11):e47891. doi: 10.1371/journal.pone.0047891. Epub 2012 Nov 14.

Abstract

Background: A defined diagnostic panel differentiated patients who had been diagnosed with chronic fatigue syndrome (CFS), based upon Fukuda/Carruthers criteria. This diagnostic panel identified an Epstein-Barr virus (EBV) subset of patients (6), excluding for the first time other similar "clinical" conditions such as cytomegalovirus (CMV), human herpesvirus 6 (HHV6), babesiosis, ehrlichiosis, borreliosis, Mycoplasma pneumoniae, Chlamydia pneumoniae, and adult rheumatic fever, which may be mistakenly called CFS. CFS patients were treated with valacyclovir (14.3 mg/kg q6h) for ≥ 12 months. Each patient improved, based upon the Functional Activity Appraisal: Energy Index Score Healthcare Worker Assessment (EIPS), which is a validated (FSS-9), item scale with high degree of internal consistency measured by Cronbach's alpha.

Methods: Antibody to EBV viral capsid antigen (VCA) IgM, EBV Diffuse Early Antigen EA(D), and neutralizing antibodies against EBV-encoded DNA polymerase and EBV-encoded dUTPase were assayed serially approximately every three months for 13-16 months from sera obtained from patients with CFS (6) and from sera obtained from twenty patients who had no history of CFS.

Results: Antibodies to EBV EA(D) and neutralizing antibodies against the encoded-proteins EBV DNA polymerase and deoxyuridine triphosphate nucleotidohydrolase (dUTPase) were present in the EBV subset CFS patients. Of the sera samples obtained from patients with CFS 93.9% were positive for EA(D), while 31.6% of the control patients were positive for EBV EA(D). Serum samples were positive for neutralizing antibodies against the EBV-encoded dUTPase (23/52; 44.2%) and DNA polymerase (41/52; 78.8%) in EBV subset CFS patients, but negative in sera of controls.

Conclusions: There is prolonged elevated antibody level against the encoded proteins EBV dUTPase and EBV DNA polymerase in a subset of CFS patients, suggesting that this antibody panel could be used to identify these patients, if these preliminary findings are corroborated by studies with a larger number of EBV subset CFS patients.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antibodies, Neutralizing / immunology*
  • Antigens, Viral
  • DNA-Directed DNA Polymerase / immunology
  • Fatigue Syndrome, Chronic / immunology*
  • Fatigue Syndrome, Chronic / virology
  • Female
  • Herpesvirus 4, Human / genetics*
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Male
  • Middle Aged
  • Pyrophosphatases / immunology

Substances

  • Antibodies, Neutralizing
  • Antigens, Viral
  • Epstein-Barr virus early antigen
  • DNA-Directed DNA Polymerase
  • Pyrophosphatases
  • dUTP pyrophosphatase