Category: Immune System

Immunological variables mediate cognitive dysfunction in gulf war veterans but not civilians with chronic fatigue syndrome

Abstract:

We explored the relationship between a set of immunological variables and a set of cognitive and functional status measures and a diagnosis of chronic fatigue syndrome (CFS) in civilians and veterans using various regression and factor analytic methods.

Our approach emphasized the extraction of a few distinct factors in order to limit statistical problems associated with doing large numbers of multiple comparisons. This approach led to our finding cytokine data grouping into type 1 and type 2 clusters. A type 2 cluster plus a T and B cell factor predicted CFS caseness for Gulf War veterans but not for civilians with CFS. When a cognitive variable, reaction time, was added into the model, both immunological factors lost statistical significance; this indicates that the cognitive variable reaction time moderated the effects of the immunological factors in predicting patient status.

We did a similar analysis on the roles of the immunological and cognitive variables in functional status using SF-36 data. Higher levels of these same two immunological factors predicted poorer general health as well as poorer physical and social functioning in Gulf War veterans but not in civilians with CFS. When the reaction time factor was added, only the lymphocyte factor remained significant. This implies that lymphocytes are directly related to functional status in Gulf War veterans with CFS, but the Th2 factor produces its effect on functional status via changes in cognitive abilities.

Copyright 2002 S. Karger AG, Basel

 

Source: Brimacombe M, Zhang Q, Lange G, Natelson B. Immunological variables mediate cognitive dysfunction in gulf war veterans but not civilians with chronic fatigue syndrome. Neuroimmunomodulation. 2002-2003;10(2):93-100. http://www.ncbi.nlm.nih.gov/pubmed/12372983

 

Peripheral blood mononuclear cell beta-endorphin concentration is decreased in chronic fatigue syndrome and fibromyalgia but not in depression: preliminary report

Abstract:

OBJECTIVE: The aim of this study was to examine the possible role of the immune system in the pathophysiology of chronic fatigue syndrome and fibromyalgia syndrome and in the differential diagnosis of depression by investigating changes in peripheral blood mononuclear cell levels of beta-endorphin, an endogenous opioid known to be involved in regulation of the immune system function.

DESIGN: Beta-endorphin concentrations were measured by radioimmunoassay in peripheral blood mononuclear cells from healthy controls (n = 8) and patients with chronic fatigue syndrome (n = 17), fibromyalgia syndrome (n = 5), or depression (n = 10).

RESULTS: Beta-endorphin concentrations were significantly lower in patients with chronic fatigue syndrome or fibromyalgia syndrome than in normal subjects and depressed patients (p <0.001 and p <0.01, respectively). They were significantly higher in depressed patients than in controls (p <0.01).

CONCLUSIONS: Evaluation of peripheral blood mononuclear cell beta-endorphin concentrations could represent a diagnostic tool for chronic fatigue syndrome and fibromyalgia and help with differential diagnosis of these syndromes versus depression. The results obtained are also consistent with the hypothesis that the immune system is activated in both chronic fatigue syndrome and fibromyalgia syndrome.

 

Source: Panerai AE, Vecchiet J, Panzeri P, Meroni P, Scarone S, Pizzigallo E, Giamberardino MA, Sacerdote P. Peripheral blood mononuclear cell beta-endorphin concentration is decreased in chronic fatigue syndrome and fibromyalgia but not in depression: preliminary report. Clin J Pain. 2002 Jul-Aug;18(4):270-3. http://www.ncbi.nlm.nih.gov/pubmed/12131069

 

Evidence for the presence of immune dysfunction in chronic fatigue syndrome

Chronic fatigue syndrome is a medically unexplained ailment characterized by new onset of fatigue accompanied by rheumatological, infectious, and neuropsychiatric symptoms. Because the ailment often begins suddenly with a flu-like presentation, early pathophysiological ideas as to cause included viral infection and immune activation. When early reports identified putative immunological abnormalities in this illness, it was given the name of chronic fatigue and immune dysfunction syndrome, or CFIDS.

The purpose of this review is to evaluate the immunological literature to determine if strong evidence to support this notion exists. We collected and reviewed 239 published papers, of which only 72 fulfilled a set of criteria for use in this review. For this review, we developed the following criteria: papers had to be published in the peer review literature; patients had to be from a group with substantial fatigue lasting at least 6 months (the vast majority fulfilled either the 1988 or the 1994 case definition of chronic fatigue syndrome [CFS]); papers had to compare CFS patients to healthy controls; and actual data had to be shown with evidence of testing for statistical significance. So, for example, when a paper reported no difference between patients and controls for some immunological variables but actual data were not included, we did not include it. Also, if a report compared patient data to normative values rather than to the study’s own control group, we did not include it.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC120010/

 

Source: Natelson BH, Haghighi MH, Ponzio NM. Evidence for the presence of immune dysfunction in chronic fatigue syndrome.  Clin Diagn Lab Immunol. 2002 Jul;9(4):747-52. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC120010/ (Full article)

 

Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions

Abstract:

In humans, activation of the primary host defense system leads to increased or decreased NREM sleep quality, depending on the degree of early immune activation. Modest elevations of certain inflammatory cytokines are found during experimental sleep loss in humans and, in addition, relatively small elevations of cytokines are seen following commencement of pharmacological treatments with clozapine, a CNS active antipsychotic agent, known to have immunomodulatory properties. Cytokines such as TNF-alpha, its soluble receptors, and IL-6, present in the periphery and the CNS, comprise a link between peripheral immune stimulation and CNS-mediated behaviors and experiences such as sleep, sleepiness, and fatigue. The debilitating fatigue experienced in chronic fatigue syndrome and related diseases may also be related to altered cytokine profiles.

 

Source: Mullington JM, Hinze-Selch D, Pollmächer T. Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions.  Ann N Y Acad Sci. 2001 Mar;933:201-10. http://www.ncbi.nlm.nih.gov/pubmed/12000021

 

Cytokines and chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) patients show evidence of immune activation, as demonstrated by increased numbers of activated T lymphocytes, including cytotoxic T cells, as well as elevated levels of circulating cytokines. Nevertheless, immune cell function of CFS patients is poor, with low natural killer cell cytotoxicity (NKCC), poor lymphocyte response to mitogens in culture, and frequent immunoglobulin deficiencies, most often IgG1 and IgG3.

Immune dysfunction in CFS, with predominance of so-called T-helper type 2 and proinflammatory cytokines, can be episodic and associated with either cause or effect of the physiological and psychological function derangement and/or activation of latent viruses or other pathogens. The interplay of these factors can account for the perpetuation of disease with remission/exacerbation cycles. A T-helper type 2 predominance has been seen among Gulf War syndrome patients and this feature may also be present in other related disorders, such as multiple chemical sensitivity. Therapeutic intervention aimed at induction of a more favorable cytokine expression pattern and immune status appears promising.

 

Source: Patarca R. Cytokines and chronic fatigue syndrome.  Ann N Y Acad Sci. 2001 Mar;933:185-200. http://www.ncbi.nlm.nih.gov/pubmed/12000020

 

Role of pathological delayed-type hypersensitivity in chronic fatigue syndrome: importance of the evaluation of lymphocyte activation by flow cytometry and the measurement of urinary neopterin

Abstract:

Chronic fatigue syndrome or benign myalgic encephalomyelitis has been extensively described and investigated. Although numerous immunological abnormalities have been linked with the syndrome, none have been found to be specific.

This article describes the detection of delayed-type hypersensitive responses to certain common environmental antigens in almost fifty per cent of patients with this syndrome. Such hypersensitivity can be detected by the intradermal administration of antigens derived from commensal organisms like the yeast Candida albicans, and then monitoring for a systemic reaction over the following six to forty eight hours. This approach can be consolidated by performing lymphocyte activation tests in parallel and measuring in vitro T-cell activation by Candida albicans antigens by three-colour flow cytometry based on CD3, CD4 and either CD69 or CD25.

Another useful parameter is the kinetics of neopterin excretion in the urine over the course of the skin test. The results showed that the intensity of the DTH response correlated with the number of T-cells activated in vitro. Various factors have been implicated in the fatigue of many patients, notably lack of sleep. However, it remains difficult to establish causality in either one direction or the other. This work is in the spirit of a multifactorial approach to the group of conditions referred to as “chronic fatigue syndrome”.

 

Source: Brunet JL, Fatoohi F, Liaudet AP, Cozon GJ. Role of pathological delayed-type hypersensitivity in chronic fatigue syndrome: importance of the evaluation of lymphocyte activation by flow cytometry and the measurement of urinary neopterin. Allerg Immunol (Paris). 2002 Feb;34(2):38-44. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/11933752

 

Cellular immunity in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

Studies elsewhere have suggested that immune dysfunction may be common in patients with chronic fatigue syndrome (CFS). The objective of this study was to assess the nature and extent of abnormalities in lymphocyte cell surface markers and NK cell activity in patients with CFS while controlling for genetic factors. A co-twin control study of immune system parameters was conducted for 22 pairs of monozygotic twins discordant for CFS and 9 healthy pairs of twins.

The CFS twins had greater numbers of CD62L(+) T cells in several T cell subsets, although these differences did not achieve statistical significance. Significantly greater variability was noted in twins discordant for CFS than in the concordant healthy twins for 20 of 48 variables examined. The monozygotic co-twin control design is of unique value because of its ability to control for genetic influences on CFS; however, additional studies will be required to further assess immune dysregulation in this illness.

 

Source: Sabath DE, Barcy S, Koelle DM, Zeh J, Ashton S, Buchwald D. Cellular immunity in monozygotic twins discordant for chronic fatigue syndrome. J Infect Dis. 2002 Mar 15;185(6):828-32. Epub 2002 Feb 28. http://jid.oxfordjournals.org/content/185/6/828.long (Full article)

 

Prevalence of allergen-specific IgE among patients with chronic fatigue syndrome

Abstract:

The prevalence of atopy among patients having chronic fatigue syndrome (CFS) has been reported to be as high as 80% in published surveys of patients with this syndrome. However, many of the reports relied on self-assessment by patients for the presence of atopy or solely used total immunoglobulin E (IgE) levels to assess the likelihood of atopy.

To more critically assess the presence of atopy among patients with CFS, testing was done for total IgE and allergen-specific IgE using the Pharmacia CAP system including 20 common allergens: trees (birch/oak/ash), grass (rye/blue), weeds (common/giant ragweed), molds (Penicillium/Aspergillus/Alternaria), dust mites (Dermatophagoides pteronyssinus/Dermatophagoides farinae), animal dander (cat/dog), and foods (egg white/milk/wheat/corn/peanut/shrimp).

Testing of 50 patients having documented CFS indicated that 78% had total IgE < 100 IU/mL, among whom 26% had a positive test for allergen-specific IgE of class I or greater for one or more allergens. Among the 22% of CFS patients having a total IgE > 100 IU/mL, 73% had a positive test for allergen-specific IgE for one or more allergens. The most commonly positive allergens were dust mites (24-26%), whereas molds (0-6%) and foods (0-4%) were rarely positive. The overall frequency of positive results for the presence of allergen-specific IgE among CFS patients was 36%, not significantly different from the normal prevalence of these antibodies in the general population (20-35%). This assessment of the prevalence of allergen-specific IgE antibodies in patients with CFS fails to support a potential association between CFS and atopy.

 

Source: Kowal K, Schacterele RS, Schur PH, Komaroff AL, DuBuske LM. Prevalence of allergen-specific IgE among patients with chronic fatigue syndrome. Allergy Asthma Proc. 2002 Jan-Feb;23(1):35-9. http://www.ncbi.nlm.nih.gov/pubmed/11894732

 

A biochemical analysis of people with chronic fatigue who have Irlen Syndrome: speculation concerning immune system dysfunction

Abstract:

This study investigated the biological basis of visual processing disabilities in adults with Chronic Fatigue Syndrome. The study involved 61 adults with symptoms of Chronic Fatigue Syndrome who were screened for visual processing problems (Irlen Syndrome) and divided into two groups according to the severity of symptoms of Irlen Syndrome.

Significant variations were identified in blood lipids and urine amino and organic acids of the two groups, which may be indicative of activation of the immune system due to some infective agent. It was suggested that metabolic profiling may help the development of more valid diagnostic categories and allow more investigation of immune system dysfunction as a possible causal factor in a range of learning and behaviour disorders.

 

Source: Robinson GL, McGregor NR, Roberts TK, Dunstan RH, Butt H. A biochemical analysis of people with chronic fatigue who have Irlen Syndrome: speculation concerning immune system dysfunction. Percept Mot Skills. 2001 Oct;93(2):486-504. http://www.ncbi.nlm.nih.gov/pubmed/11769907

 

Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue

Abstract:

To investigate whether cytokine responses may have a bearing on the symptoms and outcome of parvovirus B19 infection, circulating cytokines were measured during acute infection (n=51), follow-up of acute infection (n=39) and in normal healthy controls (n=50).

At acute B19 virus infection (serum anti-B19 IgM-positive), patients ranged in age from 4 to 54 years, with a mean age of 28.2 years. The male:female ratio was 1:4.1 and symptoms were rash (n=15), arthralgia (n=31), fatigue (n=8), lymphadenopathy (n=4), foetal hydrops (n=3), transient aplastic crisis (n=2), neutropenia (n=2), myelodysplasia (n=1), thrombocytopenia (n=1) and pancytopenia (n=1). Of these patients, 39 were contacted after a follow-up period of 2-37 months (mean of 22.5 months).

In comparison with normal controls, detectable IL-6 was associated with acute B19 virus infection (26%; P=0.0003), but not with follow-up (6%; P=0.16). Detection of interferon (IFN)-gamma was associated with acute B19 virus infection (67%; P<0.0001) and follow-up (67%; P<0.0001). Detection of tumour necrosis factor (TNF)-alpha was associated with acute B19 virus infection (49%; P<0.0001) and follow-up (56%; P<0.0001). IL-1beta was detected in acute infection (20%), but not at follow-up. At acute B19 virus infection, detection of serum/plasma IL-6 was associated with rheumatoid factor (P=0.038) and IFN-gamma (> or =7 pg/ml) was associated with fatigue in those patients of > or =15 years of age (P=0.022). At follow-up, fatigue was associated with IFN-gamma (> or =7 pg/ml) and/or TNF-alpha (> or =40 pg/ml) (P=0.0275).

Prolonged upregulation of serum IFN-gamma and TNF-alpha appears to represent a consistent host response to symptomatic B19 virus infection.

 

Source: Kerr JR, Barah F, Mattey DL, Laing I, Hopkins SJ, Hutchinson IV, Tyrrell DA. Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue. J Gen Virol. 2001 Dec;82(Pt 12):3011-9. http://www.ncbi.nlm.nih.gov/pubmed/11714978