Category: Immune System

A comprehensive immunological analysis in chronic fatigue syndrome

Abstract:

A detailed analysis of cell-mediated and antibody-mediated immunity was performed in 20 CDC-defined patients with chronic fatigue syndrome (CFS) and 20 age- and sex-matched healthy controls.

CD3+, CD4+, CD8+, and CD20+ lymphocytes were comparable in two groups. Natural killer cells as defined by CD16, CD56 and CD57 antigens were significantly reduced in CFS. A significant increase in the proportions of CD4+ ICAM 1+ T cells was observed in CFS. Monocytes from CFS displayed increased density (as determined by mean fluorescence channel numbers) of intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function associated antigen 1 (LFA-1), but showed decreased enhancing response to recombinant interferon-gamma in vitro.

The lymphocyte DNA synthesis in response to phytohaemoglobulin (PHA), Concanavalin A (Con A) and pokeweed mitogen (PWM) was normal but the response to soluble antigens was significantly reduced. Serum IgM, IgG, IgA, and IgG subclasses were normal. In vivo specific antibody response to pneumococcus vaccine was depressed in CFS.

Forty percent of patients showed titres of anti-human herpes virus 6 (anti-HHV-6) antibody higher than that in the controls (greater than or equal to 1/80). These data suggest immunological dysfunction in patients with chronic fatigue syndrome. The significance of these observations is discussed.

 

Source: Gupta S, Vayuvegula B. A comprehensive immunological analysis in chronic fatigue syndrome. Scand J Immunol. 1991 Mar;33(3):319-27. http://www.ncbi.nlm.nih.gov/pubmed/1849315

 

Changes in natural killer cell phenotype in patients with post-viral fatigue syndrome

Abstract:

We analysed peripheral blood CD56+ natural killer (NK) cell subsets in 23 carefully characterized patients with post-viral fatigue syndrome (PFS), compared with 19 healthy controls, using fluorochrome-conjugated, specific monoclonal antibodies and the FACScan.

We found significantly increased percentages of CD56+, and especially CD56bright+ NK cells in PFS patients. We also found significantly increased percentages of CD56+ high affinity interleukin-2 (IL-2) receptor (CD25)+ and CD56+ transferrin receptor (CD71+) subsets of cells, most of which also stained brightly for CD56.

Also, we found an increased percentage of CD56+ CD3+ cells, many of which stained brightly for CD56, although there was no increase in the percentage of CD56- CD3+ T cells in these patients. These observations, in conjunction with very low percentage of CD56- CD25+ cells, suggest that there is a preferential involvement of this minor subset of CD56+ CD3+ T cells in PFS.

Finally, a decreased percentage of CD56+ Fc gamma receptor (CD16)+ NK cells was identified, which suggests a reduced capacity of antibody-dependent cellular cytotoxicity in PFS patients. Subsets of CD56+ NK cells co-expressing CD2, CD4 or CD8 did not show any significant difference between PFS patients and healthy controls.

These phenotypic changes provide laboratory evidence of immunological abnormalities in this syndrome, and, we suggest, may be consistent with persistent viral infection.

 

Source: Morrison LJ, Behan WH, Behan PO. Changes in natural killer cell phenotype in patients with post-viral fatigue syndrome. Clin Exp Immunol. 1991 Mar;83(3):441-6. http://www.ncbi.nlm.nih.gov/pubmed/1706238

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1535328/

 

Chronic fatigue syndrome: I. Epstein-Barr virus immune response and molecular epidemiology

Abstract:

Patients with chronic fatigue syndrome were compared to healthy seropositive control subjects in an open study and a case-control study analyzing spontaneous transformation rates of peripheral blood lymphocytes, EBV viral genome characteristics as determined by DNA restriction fragment polymorphisms, and antibody production by Western blot analysis.

Thirty percent of patients versus 8% of control subjects underwent spontaneous transformation in the two studies. Viral genome patterns were overall similar to one another, with polymorphisms frequently present in BamHI B’, K, H, and Y fragments. Only one line was found with the EBNA-2B genotype.

Nineteen lines were found to contain viral DNA in the linear form suggesting active lytic replication. Western blot studies suggested that ill subjects made antibodies to lytic proteins more frequently than did healthy control subjects. Lack of control of EBV outgrowth in vitro is correlated with antibody evidence of active infection in vivo in some patients with chronic fatigue syndrome.

 

Source: Jones JF, Streib J, Baker S, Herberger M. Chronic fatigue syndrome: I. Epstein-Barr virus immune response and molecular epidemiology. J Med Virol. 1991 Mar;33(3):151-8. http://www.ncbi.nlm.nih.gov/pubmed/1679118

 

Nervous system-immune system communication

Abstract:

This essay is based on the premise that certain individuals may have a biologically determined propensity to respond to infection that is manifested by the development of disease such as chronic fatigue syndrome; the sequence of events that leads to this response involves the immune system. Biochemical pathways between the immune and nervous systems are reviewed, and the role of various products in the systemic circulation, including interleukin-1, pituitary hormone, and catecholamines, is highlighted. This premise could be tested by measuring levels of these substances in carefully selected patients and controls.

 

Source: Arnason BG. Nervous system-immune system communication. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S134-7. http://www.ncbi.nlm.nih.gov/pubmed/2020798

 

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

 

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

 

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

 

Natural killer cells and the post viral fatigue syndrome

Abstract:

60 patients were referred with a diagnosis of post viral fatigue syndrome (PVFS), but only 50 fulfilled strict criteria for this illness. Many lymphocyte subpopulations were normal, but there was a spectrum of natural killer (NK) cell results: 20/50 (40%) were raised; 8/50 (16%) were low;, 5/50 (10%) were low initially but normal on repeat testing; 17/50 (34%) were normal.

When patients were categorised on their NK cell results, there were significant differences in the two groups with raised or low NK cells compared to the “Not PVFS” group: the CD8 cells were increased (p less than 0.001, p less than 0.02) and the CD4/CD8 ratio was reduced (p less than 0.05) but the CD4 cells were normal.

Clinical data showed that the “Not PVFS” group were older, with less severe illness, less muscle pain and less virological evidence of infection. It is postulated that patients have low NK cells initially and then progress to normal or raised levels dependent on factors such as stress, other infections and behaviour.

 

Source: Ho-Yen DO, Billington RW, Urquhart J. Natural killer cells and the post viral fatigue syndrome. Scand J Infect Dis. 1991;23(6):711-6. http://www.ncbi.nlm.nih.gov/pubmed/1815333

 

A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome

Abstract:

PURPOSE: The chronic fatigue syndrome (CFS) is characterized by profound fatigue, neuropsychiatric dysfunction, and frequent abnormalities in cell-mediated immunity. No effective therapy is known.

PATIENTS AND METHODS: Forty-nine patients (40 with abnormal cell-mediated immunity) participated in a randomized, double-blind, placebo-controlled trial to determine the effectiveness of high-dose intravenously administered immunoglobulin G. The patients received three intravenous infusions of a placebo solution or immunoglobulin at a dose of 2 g/kg/month. Assessment of the severity of symptoms and associated disability, both before and after treatment, was completed at detailed interviews by a physician and psychiatrist, who were unaware of the treatment status. In addition, any change in physical symptoms and functional capacity was recorded using visual analogue scales, while changes in psychologic morbidity were assessed using patient-rated indices of depression. Cell-mediated immunity was evaluated by T-cell subset analysis, delayed-type hypersensitivity skin testing, and lymphocyte transformation with phytohemagglutinin.

RESULTS: At the interview conducted by the physician 3 months after the final infusion, 10 of 23 (43%) immunoglobulin recipients and three of the 26 (12%) placebo recipients were assessed as having responded with a substantial reduction in their symptoms and recommencement of work, leisure, and social activities. The patients designated as having responded had improvement in physical, psychologic, and immunologic measures (p less than 0.01 for each).

CONCLUSION: Immunomodulatory treatment with immunoglobulin is effective in a significant number of patients with CFS, a finding that supports the concept that an immunologic disturbance may be important in the pathogenesis of this disorder.

Comment in:

Intravenous immunoglobulin treatment for the chronic fatigue syndrome. [Am J Med. 1990]

Immunoglobulin treatment for chronic fatigue syndrome. [Am J Med. 1991]

Intravenous immunoglobulin treatment of chronic fatigue syndrome. [Am J Med. 1991]

Placebo responses in patients complaining of chronic fatigue. [Am J Med. 1991]

 

Source: Lloyd A, Hickie I, Wakefield D, Boughton C, Dwyer J. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.  Am J Med. 1990 Nov;89(5):561-8. http://www.ncbi.nlm.nih.gov/pubmed/2146875