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: thoughts on pathogenesis

Abstract:

Studies have shown that a proportion of patients with severe chronic infection due to Epstein-Barr virus (EBV) lack antibody to a component of EBV nuclear antigen. However, it is not clear whether this circumstance is one of cause or effect in regard to the pathogenesis of chronic fatigue syndrome (CFS); it is clearly not pathognomonic since it also occurs in persons infected with the human immunodeficiency virus and–rarely–in those with other EBV-related conditions. Stress and depression may be other pathogenetic mechanisms that could reactivate EBV and lead to CFS; examples of this phenomenon are given. The syndrome might also follow certain other viral infections as part of a process that has been called postinfectious neurasthenia. Currently, the cause(s) and cure of CFS, a common and distressing syndrome, are enigmatic and require multidisciplinary study.

 

Source: Evans AS. Chronic fatigue syndrome: thoughts on pathogenesis. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S56-9. http://www.ncbi.nlm.nih.gov/pubmed/1850544

 

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

 

Serologic and virologic epidemiology of Epstein-Barr virus: relevance to chronic fatigue syndrome

Abstract:

Patients considered to have chronic fatigue syndrome (CFS) have been reported to exhibit an increased antibody response to Epstein-Barr virus (EBV) early antigen complex and capsid antigen, findings that suggest some relationship between EBV and CFS.

However, the serologic findings have not been totally consistent among different study groups, and the antibody patterns in asymptomatic individuals may be similar. Moreover, patients with symptomatology indicative of CFS do not appear to have an abnormal burden of EBV in body fluids and manifest only a variable, mild degree of EBV-specific cell-mediated responses.

The evidence is growing that the serologic findings of an enhanced EBV state in individuals with CFS-like manifestations, as well as the subsequent reports of increased antibody titers to other viruses, reflect a generalized underlying immunologic dysfunction in these patients.

Future studies with criteria-defined CFS study groups in which determinations are made of antibody responses to newly identified EBV-associated nuclear antigen components and distinct EBV proteins in addition to specific virologic and immunologic analyses of EBV may be worthwhile as a means of clarifying the association between EBV and CFS.

 

Source: Sumaya CV. Serologic and virologic epidemiology of Epstein-Barr virus: relevance to chronic fatigue syndrome. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S19-25. http://www.ncbi.nlm.nih.gov/pubmed/1850540

 

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

 

Molecular approaches to epidemiologic evaluation of viruses as risk factors for patients who have chronic fatigue syndrome

Abstract:

One approach to understanding the chronic fatigue syndrome might be to carry out prospective studies of fatigue that occurs following infection with viral diseases of known etiology, such as influenza, hepatitis, and infectious mononucleosis. Among the viral parameters that should be evaluated are virus burden, variation of virus strain, sites of viral replication, and the state of the viral life cycle (e.g., latent or replicative). Immunologic studies should focus on the humoral and cellular responses to defined viral gene products to identify subtle, individual variations in immune recognition of specific viral subcomponents.

 

Source: Miller G. Molecular approaches to epidemiologic evaluation of viruses as risk factors for patients who have chronic fatigue syndrome. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S119-22. http://www.ncbi.nlm.nih.gov/pubmed/1850537

 

Electrophoretic analysis of human herpesvirus 6 polypeptides immunoprecipitated from infected cells with human sera

Abstract:

Proteins of human herpesvirus 6 (HHV-6) eliciting human antibody responses were examined in serum from healthy adults and patients with AIDS, chronic fatigue syndrome, Hodgkin’s disease, and Sjögren’s syndrome.

HHV-6 IgG antibody titers measured by immunofluorescence (IF) ranged from 1:10 to 1:1280. Lysates of HHV-6-infected and uninfected cells labeled with [35S]methionine, [3H]glucosamine, and 125I were immunoprecipitated with sera and analyzed electophoretically. Sera with IF titers greater than or equal to 1:20 immunoprecipitated greater than 20 [35S]methionine-labeled HHV-6 polypeptides of approximately 26-180 kDa.

At least 10 HHV-6 glycoproteins and 8 HHV-6 polypeptides associated with the surfaces of infected cells were recognized by human sera. The approximate molecular masses of glycoproteins immunoprecipitated by human sera were similar to those immunoprecipitated by monoclonal antibodies.

The labeling intensity of HHV-6 protein bands increased with increasing IF titer, and the effect was most prominent for HHV-6 glycopolypeptides. No reactivities with specific HHV-6 polypeptide(s) were characteristic of a given patient group.

These findings suggest that HHV-6 glycoproteins are good targets for human antibody responses.

 

Source: Balachandran N, Tirawatnapong S, Pfeiffer B, Ablashi DV, Salahuddin SZ. Electrophoretic analysis of human herpesvirus 6 polypeptides immunoprecipitated from infected cells with human sera. J Infect Dis. 1991 Jan;163(1):29-34. http://www.ncbi.nlm.nih.gov/pubmed/1845808

 

Analysis of clinical, epidemiologic, and laboratory data on chronic fatigue syndrome

Abstract:

Much of the research conducted on chronic fatigue syndrome (CFS) is exploratory. The researchers’ overall goal is to use clinical, epidemiologic, and laboratory data to provide clues about the etiology of this syndrome. In preparation for this symposium, a review of numerous publications on CFS has indicated that the literature generally does not reflect the application of optimal statistical methods for exploration of data.

Whenever the researchers’ aim is to generate hypotheses, modern methods designed specifically for exploratory data analysis are likely to provide greater insights into any patterns of data than are the traditional approaches to hypothesis testing. In addition, the use of formal methods of data synthesis for ongoing and future research on CFS is a means of strengthening collaborative efforts and of improving the ability of researchers to interpret the evidence available that relates to specific etiologic factors. The inclusion on the research team of experienced biostatisticians, who would oversee the statistical methods and the development of innovative analyses, is recommended.

 

Source: Redmond CK. Analysis of clinical, epidemiologic, and laboratory data on chronic fatigue syndrome. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S90-3. http://www.ncbi.nlm.nih.gov/pubmed/1826967

 

The chronic fatigue syndrome: a reappraisal and unifying hypothesis

Abstract:

The chronic fatigue syndrome is one of the most common medical problems in Western countries. Research work in virology, immunology, metabolic medicine and psychiatry in this area is reviewed and a disease model proposed. The chronic fatigue syndrome can be considered as a continuum ranging from cases with chronic viraemia on the one hand to instances of frank psychiatric illness on the other. In the majority of patients the fully evolved syndrome may involve an interaction of premorbid factors (psychological, immunological), environmental trigger factors (virus) and enhancing factors (emotional response to illness). A Venn diagram is a convenient way of expressing this concept.

 

Source: Byrne E. The chronic fatigue syndrome: a reappraisal and unifying hypothesis. Clin Exp Neurol. 1991;28:128-38. http://www.ncbi.nlm.nih.gov/pubmed/1821821