Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset

Abstract

BackgroundA 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.MethodsAntibody 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.ResultsAntibodies 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.ConclusionsThere 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.

Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease

“…(Jones and Straus 1987;Miller et al 1987). In general, individuals with aberrant (elevated) levels of EA(D) antibodies, are considered to (temporally) lack proper immunological control over endogenous latent EBV, resulting in increased viral reactivation and replication and re-expression of immunogenic early antigens, as observed in "stress" and "fatigue" cohort studies (Glaser et al 2005;Lerner et al 2012), but which are also observed in patients with certain autoimmune disorders, such as SLE and RA (Ballandraud et al 2004;Lossius et al 2012), and nasopharyngeal carcinoma (Paramita et al 2007). …”

Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome

“…Assays of blood in some patients indicate altered T helper (Th)1 and Th2 cytokine profiles, natural killer cell function and activation of the 2-5A synthetase/ RNase L antiviral pathway. [1][2][3] Infection has been reported with a wide range of viruses and bacteria, 4 including Epstein-Barr virus, [5][6][7][8] human herpes viruses 6 and 7, [9][10][11] enteroviruses, 7,12 cytomegalovirus 13,14 and lentiviruses, 15 as well as chlamydia, 7 mycoplasma 16 and borrelia species. 17 An association of ME/CFS with central nervous system (CNS) dysfunction is supported by imaging studies documenting cerebral hypoperfusion and increased white matter T2 signal consistent with chronic inflammation 18 in addition to regional differences in gray 19 and/ or white matter.…”

Combining an antiviral with rituximab in EBV-related haemophagocytic lymphohistiocytosis led to rapid viral clearance; and a comprehensive review

“…In answering (1), valacyclovir was used successfully mostly in combination with other therapies, and on grounds of immune dysregulation— including post-transplant patients, HIV, etc— in EBV-related cases of encephalitis/various forms of CNS infection,36 37 severe/complicated (eg, with hepatic involvement)/chronic infectious mononucleosis,38 hepatitis,39 chronic fatigue syndrome,40 hairy leukoplakia,41 hydroa vacciniforme,42 various types of LPDs (eg, Burkitt lymphoma),43 oral papulosis,44 periodontitis45 and lymphocytic myocarditis 46. For these conditions, which may coexist, other antiherpetics have also been used.…”