Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012;7(11):e47891.
doi: 10.1371/journal.pone.0047891. Epub 2012 Nov 14.

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

A Martin Lerner  1 , Maria E Ariza, Marshall Williams, Leonard Jason, Safedin Beqaj, James T Fitzgerald, Stanley Lemeshow, Ronald Glaser
Affiliations

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

A Martin Lerner et al. PLoS One. 2012.

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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts. A. Martin Lerner and Safedin Beqaj have ownership of CFS LLC, which owns U.S. patents for diagnosis and treatment of CFS and pending patents distinguishing Groups A and B CFS: PAT. NO. Patent Title 6,894,056 Method for diagnosing and alleviating the symptoms of chronic fatigue syndrome 6,537,997 Method for diagnosing and alleviating the symptoms of chronic fatigue syndrome 6,399,622 Method for diagnosing and alleviating the symptoms of chronic fatigue syndrome 6,258,818 Method for diagnosing and alleviating the symptoms of chronic fatigue syndrome 5,872,123 Method for diagnosing and alleviating the symptoms of chronic fatigue syndrome 5,464,020 Diagnosing and treating subacute cardiac dysfunction 5,357,968 Diagnosing and treating subacute myocarditis 5,213,106 Diagnosing and treating chronic fatigue syndrome by electrocardiographic monitoring of T-waves Pending Methods for diagnosis and treatment of chronic fatigue syndrome Ohio State University and CFS LLC have submitted a patent, EBV DNA polymerase and EBV dUTPase in EBV subset of CFS. Additionally, CFS LLC owns Certificates of Registration issued under the seal of the Copyright Office for the following work: Functional Activity Appraisal Energy Index Score. Health Care Worker Assessment; Quantitative CFS Physical Activity Assessment; Grading Scale for Energy Index Questionnaire. CFS: Based Upon Functional Capacity; EIPS: Energy Index Point Score Chart. A Functional Capacity Measurement Tool for Chronic Fatigue Syndrome (CFS) Patients. Safedin Beqaj is employed by Pathology, Inc. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide to authors.

Figures

Figure 1
Figure 1. This diagnostic decision tree identifies Group A CFS patients.
Figure 2
Figure 2. Neutralizing antibodies against EBV-encoded DNA polymerase and dUTPase in EBV subset CFS patients and controls.
Neutralizing Antibodies Against EBV-encoded DNA polymerase (units/ml) and dUTPase (units/ml×10) in patients according to control versus patients with CFS who were treated with valacyclovir.
Figure 3
Figure 3. Antibody response to EBV encoded proteins DNA polymerase and dUTPase during treatment with valacyclovir.
Duration of Antibody Response to EBV Encoded Proteins EBV DNA Polymerase and EBV dUTPase During Treatment with Valacyclovir.
See this image and copyright information in PMC

References

    1. Lerner AM, Beqaj SH, Gill K, Edington J, Fitzgerald JT, et al. (2010) An update on the management of glandular fever (infectious mononucleosis) and its sequelae caused by Epstein-Barr virus (HHV-4): new and emerging treatment strategies. Virus Adaptation and Treatment 2: 135–145.
    1. Lerner AM, Beqaj SH, Fitzgerald JT, Gill K, Gill C, et al. (2010) Subset-directed antiviral treatment of 142 herpesvirus patients with chronic fatigue syndrome. Virus Adaptation and Treatment 2: 47–57.
    1. Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, et al. (1999) A community-based study of chronic fatigue syndrome. Arch Intern Med 159: 2129–2137. - PubMed
    1. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, et al. (1994) The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 121: 953–959. - PubMed
    1. Carruthers B, Jain A, DeMeirleir K, Peterson D, Klimas NG, et al. (2003) Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Clinical Working Case Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue Syndrome 11: 7–115.

Publication types