Tag: EBV

Clinical activity of folinic acid in patients with chronic fatigue syndrome

Abstract:

A high incidence of severe B-cell immunodeficiency and chronic reactivated Epstein-Barr virus (EBV) infection in patients with chronic fatigue syndrome (CFS) is reported herein. Of the 58 patients evaluated, 100% had evidence of prior EBV exposure and 72% had evidence for reactivated EBV infection. Notably, 94% of CFS patients had B-cell immunodeficiency with a marked depletion of their CD19+IgM+ mature B-lymphocyte population. A remarkable 81% of CFS patients experienced subjective improvement of their symptoms after treatment with folinic acid (CAS 58-05-9, leucovorin). The findings provide unprecedented evidence that CFS frequently is a folinic acid responsive clinical entity accompanied by B-cell immunodeficiency and inappropriate antibody responses to EBV.

 

Source: Lundell K, Qazi S, Eddy L, Uckun FM. Clinical activity of folinic acid in patients with chronic fatigue syndrome. Arzneimittelforschung. 2006;56(6):399-404. https://www.ncbi.nlm.nih.gov/pubmed/16889122

 

Prevalence of abnormal cardiac wall motion in the cardiomyopathy associated with incomplete multiplication of Epstein-barr Virus and/or cytomegalovirus in patients with chronic fatigue syndrome

Abstract:

We reported unique incomplete herpesvirus (Epstein-Barr Virus (EBV) and/or nonstructural (HCMV) cytomegalovirus) multiplication in 2 distinct subsets of CFS patients. The CFS subsets were identified by: a) presence of IgM serum antibodies to HCMV nonstructural gene products p52 and CM2 (UL44 and UL57), and/or b) IgM serum antibodies to Epstein-Barr virus viral capsid antigen (EBV, VCA IgM).

Diagnostic IgM serum antibodies were found in two independent blinded studies involving 49 CFS patients, but the same antibodies were absent in 170 control patients (p<0.05). Abnormal 24 Hr-electrocardiographic monitoring, tachycardias at rest and, in severe chronic cases, abnormal cardiac wall motion (ACWM) were seen in these same CFS patients.

We now report a prospective consecutive case control study from 1987–1999 of cardiac dynamics as measured by radionuclide ventriculography in 98 CFS patients from 1987–1999. Controls were patients with various malignancies who were evaluated in protocols requiring radionuclide ventriculography before initiation of cardiotoxic chemotherapeutic agents.

The prevalence of abnormal cardiac wall motion (ACWM) at rest in CFS patients was 10 out of 87 patients (11.5%). With stress exercise, 21 patients (24.1%) demonstrated ACWM. Cardiac biopsies in 3 of these CFS patients with ACWM showed a cardiomyopathy. Among the controls, ACWM at rest was present in 4 out of 191 patients (2%) (p=0.0018). A progressive cardiomyopathy caused by incomplete virus multiplication of EBV and/or HCMV in CFS patients is present.

 

Source: Lerner AM, Dworkin HJ, Sayyed T, Chang CH, Fitzgerald JT, Beqaj S, Deeter RG, Goldstein J, Gottipolu P, O’Neill W. Prevalence of abnormal cardiac wall motion in the cardiomyopathy associated with incomplete multiplication of Epstein-barr Virus and/or cytomegalovirus in patients with chronic fatigue syndrome. In Vivo. 2004 Jul-Aug;18(4):417-24. http://iv.iiarjournals.org/content/18/4/417.long (Full article)

 

IgM serum antibodies to Epstein-Barr virus are uniquely present in a subset of patients with the chronic fatigue syndrome

Abstract:

BACKGROUND: A unique subset of patients with chronic fatigue syndrome (CFS) and IgM serum antibodies to cytomegalovirus (HCMV) non-structural gene products p52 and CM2 (UL 44 and UL 57) has been described.

PATIENTS AND METHODS: Fifty-eight CFS patients and 68 non-CFS matched controls were studied. Serum antibodies to EBV viral capsid antigen (VCA) IgM and EBV Early Antigen, diffuse (EA, D) as well HVCMV(V), IgM and IgG; VP (sucrose, density purified V); p52 and CM2 IgM serum antibodies were assayed.

RESULTS: Mean age of CFS patients was 44 years (75% women). Control patients were 9 years older (73% women). Serum EBV VCA IgM positive antibody titers were identified in 33 CFS patients (Group A subset EBV VCA IgM 62.3+/-8.3, neg. <20), but were not present in other CFS patients, (Group B subset EBV VCA IgM 6.8+/-0.7) controls (p<0.0001). EBV VCA IgM titers remained positive in CFS patients from Group A for 24-42 months.

CONCLUSION: Serum antibody to EBV VCA IgM may be a specific diagnostic test for a second subset of CFS patients.

 

Source: Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. IgM serum antibodies to Epstein-Barr virus are uniquely present in a subset of patients with the chronic fatigue syndrome.  In Vivo. 2004 Mar-Apr;18(2):101-6. http://iv.iiarjournals.org/content/18/2/101.long (Full article)

 

Evaluation of a recombinant line blot for diagnosis of Epstein-Barr Virus compared with ELISA, using immunofluorescence as reference method

Abstract:

A commercial line blot using recombinant antigens was compared with a commercial ELISA and ‘in-house’ IFA (reference test). Two panels were evaluated: Panel A was selected to distinguish between primary infections (89), past infections (20) and seronegatives (8) in immunocompetent individuals. In panel B, patients with a high number of reactivations were included: immunosuppressed patients (37), lymphoma (19), nasopharyngeal carcinoma (10), chronic fatigue syndrome (14). Blood donors (43) and cross-reactive sera (29) were added as controls.

Line blot and IFA were concordant in 94% of primary infections, 100% of seronegatives and 100% of past infections, similar to ELISA. Results differed significantly with regard to reactivations. When compared with IFA, the incidence of reactivations was overestimated by the blot, 24 and 58% in blood donors and cross-reactive sera, respectively. ELISA showed a similar problems with 21 and 34% indeterminate results, respectively.

The line blot is easy to carry out, has a good concordance with the reference IFA for primary infections, and is, therefore, a sufficient choice for distinguishing primary infection from seronegative and past infection. EBV reactivation assessment will require other methods such as EBV viral load.

 

Source: Gärtner BC, Fischinger JM, Roemer K, Mak M, Fleurent B, Mueller-Lantzsch N. Evaluation of a recombinant line blot for diagnosis of Epstein-Barr Virus compared with ELISA, using immunofluorescence as reference method. J Virol Methods. 2001 Apr;93(1-2):89-96. http://www.ncbi.nlm.nih.gov/pubmed/11311347

 

Lessons from a pilot study of transfer factor in chronic fatigue syndrome

Abstract:

Transfer Factor (TF) was used in a placebo controlled pilot study of 20 patients with chronic fatigue syndrome (CFS). Efficacy of the treatment was evaluated by clinical monitoring and testing for antibodies to Epstein-Barr virus (EBV) and human herpes virus-6 (HHV-6). Of the 20 patients in the placebo-controlled trial, improvement was observed in 12 patients, generally within 3-6 weeks of beginning treatment. Herpes virus serology seldom correlated with clinical response. This study provided experience with oral TF, useful in designing a larger placebo-controlled clinical trial.

 

Source: De Vinci C, Levine PH, Pizza G, Fudenberg HH, Orens P, Pearson G, Viza D. Lessons from a pilot study of transfer factor in chronic fatigue syndrome. Biotherapy. 1996;9(1-3):87-90. http://www.ncbi.nlm.nih.gov/pubmed/8993764

 

The validity and reliability of the fatigue syndrome that follows glandular fever

Abstract:

The validity and reliability of an empirically defined fatigue syndrome were tested in a prospective cohort study of 245 primary care patients, with glandular fever or an upper respiratory tract infection. Subjects were interviewed three times in the 6 months after onset. Subjects with the empirically defined fatigue syndrome were compared with those who were well and those who had a psychiatric disorder.

The validity of the fatigue syndrome was supported, separate from psychiatric disorders in general and depressive disorders in particular. Only 16% of subjects with the principal component derived fatigue factor also met criteria for a psychiatric disorder (excluding pre-morbid phobias). Compared with subjects with psychiatric disorders, subjects with the operationally defined fatigue syndrome reported more severe physical fatigue, especially after exertion, were just as socially incapacitated, had fewer mental state abnormalities, and showed little overlap on independent questionnaires. A more mild fatigue state also existed.

Both fatigue syndrome and state were more reliable diagnoses over time than depressive disorders. The empirically defined syndrome probably is a valid and reliable condition in the six months following glandular fever.

 

Source: White PD, Grover SA, Kangro HO, Thomas JM, Amess J, Clare AW. The validity and reliability of the fatigue syndrome that follows glandular fever. Psychol Med. 1995 Sep;25(5):917-24. http://www.ncbi.nlm.nih.gov/pubmed/8588010

 

The existence of a fatigue syndrome after glandular fever

Abstract:

This prospective cohort study was designed to test whether a distinct fatigue syndrome existed after the onset of glandular fever.

Two hundred and fifty primary care patients, with either glandular fever or an ordinary upper respiratory tract infection (URTI) were interviewed three times in the 6 months after the clinical onset of their infection. At each interview a standardized psychiatric interview was given and physical symptoms were assessed. There were 108 subjects with and Epstein-Barr virus (EBV) infection; 83 subjects had glandular fever not caused by EBV and 54 subjects had an ordinary URTI. Five subjects were excluded because they had no evidence of an infection.

Principal components analyses of symptoms supported the existence of a fatigue syndrome, particularly in the two glandular fever groups. The addition of symptoms not elicited by the standard interviews gave the full syndrome. This included physical and mental fatigue, excessive sleep, psychomotor retardation, poor concentration, anhedonia, irritability, social withdrawal, emotional lability, and transient sore throat and neck gland swelling with pain. A fatigue syndrome probably exists after glandular fever.

 

Source: White PD, Thomas JM, Amess J, Grover SA, Kangro HO, Clare AW. The existence of a fatigue syndrome after glandular fever. Psychol Med. 1995 Sep;25(5):907-16. http://www.ncbi.nlm.nih.gov/pubmed/8588009

 

The disease associations of the antibody response against the Epstein-Barr virus transactivator protein ZEBRA can be separated into different epitopes

Abstract:

The BamHI-Z-encoded Epstein-Barr virus (EBV) replication activator (ZEBRA) is a key mediator of the switch from latency to productive cycle in EBV virus. Antibodies against ZEBRA are a marker of EBV reactivation and are regularly found among patients with infectious mononucleosis (IM) or nasopharyngeal carcinoma (NPC), but are only rarely found among healthy EBV-seropositive donors.

In order to define the serologically reactive epitopes in the ZEBRA protein, we synthesized a set of overlapping peptides and tested them for reactivity with serum samples from EBV-seronegative persons, patients with NPC, IM, chronic fatigue syndrome, lymphoma or from healthy donors. Three major EBV-specific epitopes were found.

These epitopes were further defined and optimized using substitution or truncation analogues of the peptides. Reactivity with epitope number 22 was found in 63% of NPC patients’ sera, with < 2% of healthy donors’ sera being positive. Serological reactivity with epitope number 19 was associated with IM (57% positive, 5% healthy donors positive).

Serum antibodies against epitope 1 were found among healthy donors, but were significantly elevated among patients with NPC, IM or lymphomas. In conclusion, different serologically reactive epitopes in the ZEBRA protein associate with different EBV-associated diseases.

 

Source: Tedeschi R, Foong YT, Cheng HM, dePaoli P, Lehtinen T, Elfborg T, Dillner J. The disease associations of the antibody response against the Epstein-Barr virus transactivator protein ZEBRA can be separated into different epitopes. J Gen Virol. 1995 Jun;76 ( Pt 6):1393-400. http://www.ncbi.nlm.nih.gov/pubmed/7540196

Note: You can read the full study HERE.

 

Epstein-Barr virus (EBV) and the chronic fatigue syndrome: normal virus load in blood and normal immunologic reactivity in the EBV regression assay

Abstract:

The etiology of chronic fatigue syndrome (CFS) is unknown. Some patients have high antibody titers to viral capsid antigen (VCA) and early antigen (EA) of Epstein-Barr virus (EBV), suggesting that reactivation of EBV is involved. We investigated virus load (spontaneous transformation) and immunologic regression of EBV-induced transformation in peripheral blood mononuclear cells (PBMCs) from 10 selected patients with CFS who had high antibody titers to VCA and EA. The outcome was compared with that for nine healthy controls and one patient with severe chronic active EBV infection (SCAEBV). There were no significant differences in viral load between patients and healthy controls. Immunologic regression of in vitro-transformed PBMCs was also equally efficient in patients and controls. The SCAEBV-infected patient and two controls, who were all seronegative for EBV, showed impaired regression. In conclusion, we were unable to demonstrate a role for reactivation of EBV in CFS, even in selected patients with high titers of antibody to VCA and EA of EBV.

 

Source: Swanink CM, van der Meer JW, Vercoulen JH, Bleijenberg G, Fennis JF, Galama JM. Epstein-Barr virus (EBV) and the chronic fatigue syndrome: normal virus load in blood and normal immunologic reactivity in the EBV regression assay. Clin Infect Dis. 1995 May;20(5):1390-2. http://www.ncbi.nlm.nih.gov/pubmed/7620030

 

Cytomegalovirus and Epstein-Barr Virus Infection as a Cause of Chronic Fatigue Syndrome in Travelers to Tropical Countries

Although for research purposes the clinical definition of the chronic fatigue syndrome (CFS) is well established, many aspects of this illness such as its etiology, pathogenesis, and treatment are still unknown. Even the clinical definition is subject to controversy, and although much effort has been expended in the investigation of the clinical aspects of the syndrome, little is known about its epidemiology.

This article considers a cohort of 14 cases that meet the criteria of CFS.The signs and symptoms of CFS in these cases manifested during, or shortly after, a trip to a tropical country.These signs and symptoms appeared to be related to cytomegalovirus (MV) or Epstein-Barr virus infection (EBV).

You can read the full article here: http://jtm.oxfordjournals.org/content/jtm/2/1/41.full.pdf

 

Source: Gascón J, Marcos T, Vidal J, Garcia-Forcada A, Corachán M. Cytomegalovirus and Epstein-Barr Virus Infection as a Cause of Chronic Fatigue Syndrome in Travelers to Tropical Countries. J Travel Med. 1995 Mar 1;2(1):41-44. http://www.ncbi.nlm.nih.gov/pubmed/9815359