Review of laboratory findings for patients with chronic fatigue syndrome

Abstract:

Various abnormalities revealed by laboratory studies have been reported in adults with chronic fatigue syndrome. Those most consistently reported include depressed natural killer cell function and reduced numbers of natural killer cells; low levels of circulating immune complexes; low levels of several autoantibodies, particularly antinuclear antibodies and antithyroid antibodies; altered levels of immunoglobulins; abnormalities in number and function of lymphocytes; and modestly elevated levels of two Epstein-Barr virus-related antibodies, immunoglobulin G to viral capsid antigen and to early antigen.

 

Source: Buchwald D, Komaroff AL. Review of laboratory findings for patients with chronic fatigue syndrome. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S12-8. http://www.ncbi.nlm.nih.gov/pubmed/1902321

 

Chronic fatigue syndrome in northern Nevada

Abstract:

The clinical and laboratory findings from studies of patients with chronic fatigue syndrome (CFS) from northern Nevada are summarized. Physicians caring for these patients have estimated that greater than 400 patients with CFS from northern Nevada and nearby communities in California were identified between 1984 and 1988.

As a result of these studies, a cluster of clinical and laboratory features associated with the illness in moderately to severely affected patients has been identified: profound fatigue of prolonged duration; cervical lymphadenopathy; recurrent sore throat and/or symptoms of influenza; loss of cognitive function manifested by loss of memory and loss of ability to concentrate; myalgia; impairment of fine motor skills; abnormal findings on magnetic resonance imaging brain scan; depressed level of antibody to Epstein-Barr virus (EBV) nuclear antigen; elevated level of antibody to EBV early antigen restricted component; elevated ratio of CD4 helper to CD8 suppressor cells; and strong evidence of association of this syndrome with infection with human herpesvirus 6.

More-serious and longer-lasting neurologic impairments, including seizures, psychosis, and dementia, have also been observed in some of these patients.

 

Source: Daugherty SA, Henry BE, Peterson DL, Swarts RL, Bastien S, Thomas RS. Chronic fatigue syndrome in northern Nevada. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S39-44. http://www.ncbi.nlm.nih.gov/pubmed/1850542

 

Serologic and immunologic responses in chronic fatigue syndrome with emphasis on the Epstein-Barr virus

Abstract:

Although patients with chronic fatigue syndrome (CFS) can be diagnosed by clinical criteria, the lack of specific laboratory criteria delays or prevents the diagnosis and contributes to the quasi-disease status of the syndrome.

A resurgence of interest in the syndrome has followed reports suggesting that CFS may be associated with chronic active infection due to the Epstein-Barr virus. Analysis of reports to date shows that the mean titers of antibodies to viral capsid antigen and to early antigen are greater for patients with CFS than for healthy individuals; this is particularly evident in cases for which serial samples were tested.

However, these differences do not prove the cause of CFS. Cell-mediated immune responses in patients with CFS vary from study to study, and the number and function of natural killer cells in those patients are the most variable factors. Rates of isolation of virus from saliva do not differ, but in one comparison study with a large number of subjects, more lymphocytes that contained virus were isolated from patients than from controls.

Other viruses, such as the Coxsackie B virus, have been implicated as causes of CFS in studies from Great Britain. The use of a working definition of CFS and standardized tests to address abnormalities revealed by laboratory tests among homogeneous populations should allow determination of useful tests for the diagnosis of CFS and studies of its mechanisms.

 

Source:  Jones JF. Serologic and immunologic responses in chronic fatigue syndrome with emphasis on the Epstein-Barr virus. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S26-31. http://www.ncbi.nlm.nih.gov/pubmed/1850541

 

Detection of Epstein-Barr virus with molecular hybridization techniques

Abstract:

The cord-blood transformation assay remains the standard method for detecting Epstein-Barr virus (EBV) in secretions. However, newer methods are much faster and more sensitive, although most are still regarded as research procedures. The most useful of these are Southern blot hybridization, particularly the variation that employs terminal genomic probe analysis; in situ cytohybridization; and polymerase chain reaction analyses. Use of these methods alone or in combination should disclose the infected cell type, whether the infection is productive or latent, and the presence of multiple strains of EBV. Such information may help establish whether EBV is a causal agent in chronic fatigue syndrome.

 

Source: Pagano JS. Detection of Epstein-Barr virus with molecular hybridization techniques. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S123-8. http://www.ncbi.nlm.nih.gov/pubmed/1850538

 

Dual infections of the immune system in patients with chronic active Epstein-Barr virus infection mimicking chronic fatigue syndrome

Abstract:

The etiologic bases of CFS are undetermined at the present time. It is very important to distinguish the patients with CFS as defined by the Centers for Disease Control (CDC) case definition of Holmes et al. from patients with physical and laboratory findings suggesting dual infections and/or underlying immunodeficiency. Particularly fruitful might be a longitudinal immunovirologic study of patients who exhibit CFS following a well-documented viral infection.

 

Source: Purtilo DT. Dual infections of the immune system in patients with chronic active Epstein-Barr virus infection mimicking chronic fatigue syndrome. Can Dis Wkly Rep. 1991 Jan;17 Suppl 1E:29-32. http://www.ncbi.nlm.nih.gov/pubmed/1669350

 

Clinical and laboratory findings in the Paul-Bunnell negative glandular fever-fatigue syndrome

Abstract:

Forty-one patients with recurrent fatigue were studied for evidence of symptom clustering, abnormal laboratory findings and infection with novel viruses. Symptom enquiry and investigations were repeated 4 months later.

Four patients were found to have diseases compatible with their symptoms. In those remaining, an initial acute onset of symptoms was associated with an intermittent course, tender glands and a raised number of T suppressor lymphocytes. Raised numbers of T suppressor lymphocytes at follow-up correlated with resolution of symptoms. Antibodies to human herpesvirus 6 (HHV-6) were found in 75% of the patients as compared to 53% of a control group and more patients than controls were strongly seropositive.

Some patients with chronic fatigue have a pattern of illness which suggests glandular fever, although acute infection with Epstein-Barr virus (EBV) is not demonstrated. Primary or reactivation infection with HHV-6 may have a role in this syndrome.

 

Source:  Read R, Larson E, Harvey J, Edwards A, Thomson B, Briggs M, Fox J. Clinical and laboratory findings in the Paul-Bunnell negative glandular fever-fatigue syndrome. J Infect. 1990 Sep;21(2):157-65. http://www.ncbi.nlm.nih.gov/pubmed/2172387

 

Chronic fatigue syndrome

Abstract:

Reports on conditions of chronic fatigue associated with other somatopsychic symptoms after acute viral infections have led to the hypothesis of a “chronic fatigue syndrome” (CFS). Historical disease descriptions, like e.g. “myalgic encephalomyelitits”, were updated by means of modern virological diagnostic techniques and data analysis.

Several viral agents like enteroviruses, Epstein-Barr virus, Human-Herpesvirus 6 and other herpesviruses have been implicated for possible underlying infections. A preliminary disease definition by the Center for Disease Control (CDC) seeks to provide a rational basis for further etiological studies. In fact, there is growing consensus that the syndrome comprises various separate disease entities and causative agents.

Today we can tentatively differentiate a “chronic mononucleosis” after infection with Epstein-Barr virus, an etiologically undetermined “postviral fatigue syndrome” and a fatigue syndrome of the myalgic type after Coxsackie-B virus infection. Furthermore, a valid diagnosis of CFS must be based on the exclusion of defined other diseases and the awareness of dealing with a hypothetical concept. As a result, current knowledge does not yet allow specific therapeutic recommendations.

 

Source: Ewig S, Dengler HJ. Chronic fatigue syndrome. Klin Wochenschr. 1990 Aug 17;68(16):789-96. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/2170741

 

Isolation of human herpesvirus-6 from clinical specimens using human fibroblast cultures

Abstract:

The isolation and characterization of human herpesvirus-6 (HHV-6) has been hindered by the lack of cell lines useful for its rapid propagation. Recently, we have reported that the MRC-5 cell line (human diploid lung fibroblasts) was susceptible for HHV-6 infection.

In this study, we report on the isolation of HHV-6 from the peripheral blood or buffy coat of three chronic fatigue syndrome patients, one post-liver transplant patient, and one severe chronic active Epstein-Barr virus syndrome patient using the MRC-5 cell line.

Additionally, it was observed by Southern blot hybridization studies that four of five isolates had different restriction enzyme fragment patterns than the isolate obtained from the National Institutes of Health with Eco RI.

These data suggest the usefulness of the MRC-5 cell line in the isolation and characterization of HHV-6 from various patients.

 

Source: Luka J, Okano M, Thiele G. Isolation of human herpesvirus-6 from clinical specimens using human fibroblast cultures. J Clin Lab Anal. 1990;4(6):483-6. http://www.ncbi.nlm.nih.gov/pubmed/2178187

 

Severe chronic active Epstein-Barr virus infection syndrome and adenovirus type-2 infection

Abstract:

Four patients from 4 to 24 years of age (3 males, 1 female) with generalized lymphadenopathy, hepatosplenomegaly, and intermittent fever associated with chronic active Epstein-Barr virus (EBV) infection were investigated.

Laboratory data showed polyclonal gammopathy and a tendency for bone marrow suppression. Noteworthy were the extremely elevated immunoglobulin G (IgG) antibody titers to Epstein-Barr viral capsid antigen (VCA) (range, 10,240-81,920) and early antigen (EA) (range, 1,280-40,960). All patients had IgA antibodies to VCA and EA. Subtle, heterogeneous immune functional defects were observed in all four patients. Another unusual feature was our inability to establish spontaneous or B95-8 EBV-immortalized lymphoblastoid cell lines (LCLs) due to a marked cytopathic effect (CPE). Thus, we investigated for other viruses.

Both IgG and IgM antibodies to adenovirus type-2 (Ad-2) were positive by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) test, suggesting recent or activated Ad-2 infection had occurred. Dual active EBV and Ad-2 infections were likely etiologic in this severe chronic active EBV infection syndrome.

 

Source: Okano M, Thiele GM, Purtilo DT. Severe chronic active Epstein-Barr virus infection syndrome and adenovirus type-2 infection. Am J Pediatr Hematol Oncol. 1990 Summer;12(2):168-73. http://www.ncbi.nlm.nih.gov/pubmed/2165745

 

The chronic fatigue syndrome: definition, current studies and lessons for fibromyalgia research

Abstract:

Chronic fatigue syndrome (CFS) is characterized by chronic, debilitating fatigue lasting greater than 6 months. Frequent chronic and recurrent findings include fever, pharyngitis, myalgias, adenopathy, arthralgias, difficulties in cognition and disorders of mood. In the majority of patients, the illness starts suddenly with an acute, “flu-like” illness.

The following laboratory abnormalities are seen with some frequency, although none are seen in all patients: lymphocytosis, atypical lymphocytosis, monocytosis, elevation of hepatocellular enzymes, low levels of antinuclear antibodies, varying levels of antithyroid antibodies, partial hypergammaglobulinemia, elevated CD4:CD8 ratio, decreased cytolytic activity of natural killer cells, and low levels of immune complexes. Clinical and serologic studies suggest an association of CFS with all of the human herpesviruses, particularly Epstein-Barr virus (EBV) and the recently discovered human B lymphotropic virus (HBLV) or human herpesvirus 6; neither EBV nor HBLV has yet been shown to play a causal role in the illness.

Preliminary evidence suggests that many of these features of CFS also are seen in patients with fibromyalgia.

 

Source: Komaroff AL, Goldenberg D. The chronic fatigue syndrome: definition, current studies and lessons for fibromyalgia research. J Rheumatol Suppl. 1989 Nov;19:23-7. http://www.ncbi.nlm.nih.gov/pubmed/2691680