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

 

Case control study of chronic fatigue in pediatric patients

Abstract:

OBJECTIVE: To determine the demographic characteristics, medical features, psychological profile, and natural history of children with chronic fatigue.

DESIGN: Case control study.

SETTING: Pediatric Infectious Diseases Clinic of Kosair Children’s Hospital, 1990 to 1992.

PARTICIPANTS: Forty-four patients referred for persistent fatigue were evaluated. Twenty patients participated in a psychological study; 20 healthy controls of similar age and gender were recruited from community pediatric practices and 20 matched depressed controls were recruited from university psychiatry services (subjects were treated as groups in the analyses).

MEASURES: Demographic data were obtained for all referred patients. Those with fatigue for at least 2 months and no alternative diagnosis received a detailed history, physical, and battery of laboratory tests (complete blood count, sedimentation rate, chemistry panel, chest X-ray thyroid stimulating hormone, thyroxine, anti-nuclear antibodies, urinalysis, immunoglobulins, and Epstein-Barr virus (EBV), toxoplasma, and cytomegalovirus serologies). Psychological study participants completed the following: background structured interview; Kaufman Brief Intelligence Test; Children’s Depression Inventory; Child Behavior Checklist; Youth Self Report; Diagnostic Interview for Children and Adolescents-Revised; mail-in follow-up survey.

RESULTS: The median age of fatigue patients was 14.3 years; 60% were female, 96% white, and 87% from the mid/upper socioeconomic status (SES). Fatigue patients were demographically similar to 21 patients referred for infectious mononucleosis (IM) but were older than other clinic patients (P < .0001). White race (P = .0568) and mid/upper SES (P = .0403) were over-represented among fatigue patients compared to patients referred for other diagnoses. Of 36 patients meeting criteria for further study, 5 had an IM-like illness including evidence of recent EBV infection. For the remaining 31 patients, clinical and laboratory evaluations were unrevealing. Psychological study subjects reported marked declines in quality-of-life and scored high on measures of internalizing, withdrawal, and social isolation. Nine met diagnostic criteria for depression, although depressive symptoms were not as prominent as those reported by depressed controls. Fatigue subjects scored higher on somatization than both control groups. The follow-up survey indicated symptomatic improvement in most patients.

CONCLUSIONS: Chronic fatigue was a common reason for referral, with over-representation of white children from mid/upper SES. After exclusion of EBV-associated IM, screening laboratory tests were not helpful in establishing specific organic diagnoses. Whereas the natural history was favorable, chronic fatigue resulted in major quality-of-life changes and was associated with significant levels of psychosocial distress.

IMPLICATIONS: Psychological evaluation is warranted in these patients, as some may have treatable psychological conditions. Given the absence of proved medical therapies, psychosocial interventions to improve quality-of-life should be studied.

 

Source: Carter BD, Edwards JF, Kronenberger WG, Michalczyk L, Marshall GS. Case control study of chronic fatigue in pediatric patients. Pediatrics. 1995 Feb;95(2):179-86. http://www.ncbi.nlm.nih.gov/pubmed/7838632

 

Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome

Abstract:

To test for an association between chronic fatigue syndrome (CFS) and infections with Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7), antibodies to these viruses were tested in the serum from three groups of individuals: (1) 10 CFS patients with chronic fatigue beginning with a clinical pattern of acute infectious mononucleosis [IM; true chronic IM (CIM)]; (2) 10 CFS patients whose illness did not start with acute IM (non-CIM), and (3) healthy controls.

High EBV antibody titers were demonstrated in most patients. Antibodies to ZEBRA, a product of the immediate early EBV gene BZLF1, were detected in the serum of CFS patients at a higher frequency than in healthy controls. Antibody titers to HHV-6 and HHV-7 were also higher in the patients with CFS than in the controls. These results are consistent with the view that CFS patients may have reactivations of EBV, HHV-6 and HHV-7.

 

Source: Sairenji T, Yamanishi K, Tachibana Y, Bertoni G, Kurata T. Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome. Intervirology. 1995;38(5):269-73. http://www.ncbi.nlm.nih.gov/pubmed/8724857