Category: Immune System

Immune modulation with a staphylococcal preparation in fibromyalgia/chronic fatigue syndrome: relation between antibody levels and clinical improvement

Abstract:

The aims of this study were to evaluate the serological response to treatment with staphylococcal vaccine in fibromyalgia/chronic fatigue syndrome patients and to explore the relationship between serological response and clinical effect.

Twenty-eight patients, half of whom served as controls, were recruited from a 6-month randomised trial in which repeated administration of the staphylococcal toxoid vaccine Staphypan Berna (Berna Biotech, Switzerland) was tested against placebo. Antibody status against extracellular toxins/enzymes, cell-wall components, and enterotoxins was evaluated at baseline and at endpoint. The clinical response to treatment was recorded in rating scales.

In the group receiving active treatment, significant serological changes were recorded, whereas no significant changes were found in controls. Treatment led to a significantly increased capacity of serum to neutralise alpha-toxin and a significant increase in serum IgG to alpha-toxin and lipase. Furthermore, the increase in these parameters combined paralleled the improvement in clinical outcome. Thus, the greater the serological response, the greater was the clinical effect.

In conclusion, this explorative study has shown that repeated administration of the Staphypan Berna vaccine in patients with fibromyalgia/chronic fatigue syndrome causes a serological response to several staphylococcal antigens, particularly to certain extracellular toxins and enzymes. The results further show that this response is related to the clinical outcome of treatment.

 

Source: Zachrisson O, Colque-Navarro P, Gottfries CG, Regland B, Möllby R. Immune modulation with a staphylococcal preparation in fibromyalgia/chronic fatigue syndrome: relation between antibody levels and clinical improvement. Eur J Clin Microbiol Infect Dis. 2004 Feb;23(2):98-105. Epub 2004 Jan 20. http://www.ncbi.nlm.nih.gov/pubmed/14735403

 

Influenza vaccination: is it appropriate in chronic fatigue syndrome?

Abstract:

Chronic fatigue syndrome (CFS) is a recognized clinical illness of unknown cause and pathophysiologic mechanisms. Immunizing patients against influenza would seem to be a prudent strategy since infection has been associated with symptom exacerbation. However, patients with CFS have demonstrated variable abnormalities in the immune system, the clinical significance of which is unclear. Anecdotal information has suggested that, due to the etiologic uncertainty surrounding CFS, many patients reject immunization, fearful of untoward effects. This article attempts to clarify the situation by reviewing immunologic findings in CFS and influenza vaccines in current use. Results from a recent survey of perceptions of patients with CFS regarding immunization revealed that 31% felt immunization was neither safe nor beneficial. This opinion was universal in those patients who had never received influenza vaccine. Among patients who had received vaccine and experienced an adverse effect, 26% felt the vaccine was safe and 28% felt it was beneficial. Among those who had received vaccine without an adverse effect, 45% believed the vaccine was safe, and 55% felt it was effective. CFS patients as a group expressed concern that influenza vaccine would alter an already dysfunctional immune system, or worsen CFS symptoms.

Significantly more patients with CFS who had never received influenza vaccine voiced this opinion than did patients who had received immunization for influenza in the past. Contrary to the opinions expressed by the sample, clinical trials in CFS have yet to find that any type of immunization has produced a deleterious effect on symptoms or functioning. Moreover, patients with CFS in a randomized, placebo-controlled, double-blind trial of influenza immunization produced an antibody titer in the protective range to inactivated trivalent influenza vaccine, although the geometric mean titer was slightly blunted compared with healthy vaccinees.

Although patients with CFS in placebo and active groups reported four times the number of post-injection adverse effects of healthy vaccinees, data re-analysis revealed that this finding was related to the overlap of common, post-influenza immunization symptoms and CFS constitutional symptoms. CFS is a poorly understood illness and some patients may believe in causal theories that lead to the rejection of disease prevention strategies such as immunization. However, influenza immunization appears to provide protective antibody levels without worsening CFS symptoms or causing excessive adverse effects. Efforts to motivate patients with CFS to obtain annual influenza immunization should take into account illness perceptions and concentrate on education based on placebo-controlled trials.

 

Source: Sleigh KM, Marra FH, Stiver HG. Influenza vaccination: is it appropriate in chronic fatigue syndrome? Am J Respir Med. 2002;1(1):3-9. http://www.ncbi.nlm.nih.gov/pubmed/14720070

 

Effect of bojungikki-tang on lipopolysaccharide-induced cytokine production from peripheral blood mononuclear cells of chronic fatigue syndrome patients

Abstract:

Bojungikki-tang (BIT) has been widely used to treat patients suffering from chronic fatigue syndrome (CFS). However, its effect has not been yet investigated experimentally. Based upon the clinical presentation of CFS, we hypothesized that cytokines may play a role in the pathogenesis of the disease. We studied the effect of BIT on lipopolysaccharide (LPS)-induced various cytokines production in peripheral blood mononuclear cells (PBMC) of CFS patients. Bojungikki-tang (1 mg/mL) significantly inhibited LPS-induced tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta1 production by 63.55% +/- 0.19%, 55.06% +/- 0.27%, 48.23% +/- 0.48%, 54.09% +/- 0.76%, respectively (P < 0.05). Bojungikki-tang showed a slightly lower inhibitory effect of LPS-induced Interferon (IFN)-gamma production. These results suggest that BIT may be useful in treating fatigue associated with chronic diseases.

 

Source: Shin HY, Shin CH, Shin TY, Lee EJ, Kim HM. Effect of bojungikki-tang on lipopolysaccharide-induced cytokine production from peripheral blood mononuclear cells of chronic fatigue syndrome patients. Immunopharmacol Immunotoxicol. 2003 Nov;25(4):491-501. http://www.ncbi.nlm.nih.gov/pubmed/14686792

 

Identification of novel expressed sequences, up-regulated in the leucocytes of chronic fatigue syndrome patients

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is an increasing medical phenomenon of unknown aetiology leading to high levels of chronic morbidity. Of the many hypotheses that purport to explain this disease, immune system activation, as a central feature, has remained prominent but unsubstantiated. Supporting this, a number of important cytokines have previously been shown to be over-expressed in disease subjects. The diagnosis of CFS is highly problematic since no biological markers specific to this disease have been identified. The discovery of genes relating to this condition is an important goal in seeking to correctly categorize and understand this complex syndrome.

OBJECTIVE: The aim of this study was to screen for changes in gene expression in the lymphocytes of CFS patients.

METHODS: ‘Differential Display’ is a method for comparing mRNA populations for the induction or suppression of genes. In this technique, mRNA populations from control and test subjects can be ‘displayed’ by gel electrophoresis and screened for differing banding patterns. These differences are indicative of altered gene expression between samples, and the genes that correspond to these bands can be cloned and identified. Differential display has been used to compare expression levels between four control subjects and seven CFS patients.

RESULTS: Twelve short expressed sequence tags have been identified that were over-expressed in lymphocytes from CFS patients. Two of these correspond to cathepsin C and MAIL1 – genes known to be upregulated in activated lymphocytes. The expression level of seven of the differentially displayed sequences have been verified by quantifying relative level of these transcripts using TAQman quantitative PCR.

CONCLUSION: Taken as a whole, the identification of novel gene tags up-regulated in CFS patients adds weight to the idea that CFS is a disease characterized by subtle changes in the immune system.

 

Source: Powell R, Ren J, Lewith G, Barclay W, Holgate S, Almond J. Identification of novel expressed sequences, up-regulated in the leucocytes of chronic fatigue syndrome patients. Clin Exp Allergy. 2003 Oct;33(10):1450-6. http://www.ncbi.nlm.nih.gov/pubmed/14519154

 

Cytokines in parvovirus B19 infection as an aid to understanding chronic fatigue syndrome

Abstract:

Human parvovirus B19 infection has been associated with various clinical manifestations of a rheumatic nature such as arthritis, fatigue, and chronic fatigue syndrome (CFS), which can persist for years after the acute phase.

The authors have demonstrated recently that acute B19 infection is accompanied by raised circulating levels of IL-1b, IL-6, TNF-a, and IFN-g and that raised circulating levels of TNF-a and IFN-g persist and are accompanied by MCP-1 in those patients who develop CFS.

A resolution of clinical symptoms and cytokine dysregulation after intravenous immunoglobulin (IVIG) therapy, which is the only specific treatment for parvovirus B19 infection, also has been reported. Although CFS may be caused by various microbial and other triggers, that triggered by B19 virus is clinically indistinguishable from idiopathic CFS and exhibits similar cytokine abnormalities and may represent an accessible model for the study of CFS.

 

Source: Kerr JR, Tyrrell DA. Cytokines in parvovirus B19 infection as an aid to understanding chronic fatigue syndrome. Curr Pain Headache Rep. 2003 Oct;7(5):333-41. http://www.ncbi.nlm.nih.gov/pubmed/12946285

 

Complement activation in a model of chronic fatigue syndrome

Abstract:

BACKGROUND: A need exists to identify biological markers in chronic fatigue syndrome (CFS).

OBJECTIVE: To use an exercise and/or allergen challenge to induce the symptoms of CFS and to identify a biological marker that correlates with these symptoms.

METHODS: Patients with CFS (n = 32) and age-matched, normal control patients (n = 29) exercised for 20 minutes on a stationary bike at 70% of their predicted max work load (Watts). Patients from each group with positive skin test results were also challenged with intranasally administered relevant allergens. Symptoms were recorded for 2 weeks before and 1 week after each challenge, using 3 different instruments. Blood samples were taken before, and 0, 1, 6, and 24 hours after challenges. Levels of complement split products, cell-associated cytokines, and eosinophilic cationic protein were measured. Mean preexercise and postexercise symptom scores were evaluated for each group.

RESULTS: Exercise challenge induced significant increases of the complement split product C4a, but not C3a or C5a, at 6 hours after exercise only in the CFS group (P <.01), regardless of allergy status. Mean symptom scores were significantly increased after exercise through the use of a daily diary (P <.03) and a weekly diary (P <.01) for the CFS group only. Mean scores for the Multidimensional Fatigue Inventory categories “reduced activity” and “mental fatigue” were significantly increased in the CFS group only (P <.04 and P <.02, respectively).

CONCLUSIONS: Exercise challenge may be a valuable tool in the development of diagnostic criteria and tests for CFS. Establishment of a role for complement activation products as markers or participants in production of illness require further study.

 

Source: Sorensen B, Streib JE, Strand M, Make B, Giclas PC, Fleshner M, Jones JF. Complement activation in a model of chronic fatigue syndrome. J Allergy Clin Immunol. 2003 Aug;112(2):397-403. http://www.ncbi.nlm.nih.gov/pubmed/12897748

 

Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome

Abstract:

The disturbance of the central nervous system and immunological abnormalities have been suggested in patients with chronic fatigue syndrome(CFS). We focused on immunological abnormalities against neurotransmitter receptors in CFS.

Using a sensitive radioligand assay, we examined serum autoantibodies to recombinant human muscarinic cholinergic receptor 1 (CHRM1), mu-opioid receptor (OPRM1), 5-hydroxytryptamine receptor 1A (HTR1A), and dopamine receptor D2 (DRD2) in patients with CFS (n=60) and results were compared with those in patients with autoimmune disease (n=33) and in healthy controls (n=30).

The mean anti-CHRM1 antibody index was significantly higher in patients with CFS (p<0.0001) and autoimmune disease (p<0.05) than that in healthy controls, and positive reaction was found in 53.3% of patients with CFS. Anti-OPRM1 antibodies, anti-HTR1A antibodies, and anti-DRD2 antibodies were found in 15.2, 1.7, and 5.0% of patients with CFS, respectively. Anti-nuclear antibodies were found in 56.7% (34/60) of patients with CFS, but anti-nuclear antibody titers did not correlate with the activities of the above four autoantibodies.

The patients with positive autoantibodies to CHRM1 had a significantly higher mean score (1.81) of ‘feeling of muscle weakness’ than negative patients (1.18) among CFS patients (p<0.01). Higher scores on ‘painful node’, ‘forgetfulness’, and ‘difficulty thinking’ were also found in CFS patients with anti-CHRM1 antibodies but did not reach statistical significance.

In conclusion, autoantibodies to CHRM1 were detected in a large number of CFS patients and were related to CFS symptoms. Our findings suggested that subgroups of CFS are associated with autoimmune abnormalities of CHRM1.

 

Source: Tanaka S, Kuratsune H, Hidaka Y, Hakariya Y, Tatsumi KI, Takano T, Kanakura Y, Amino N. Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome. Int J Mol Med. 2003 Aug;12(2):225-30. http://www.ncbi.nlm.nih.gov/pubmed/12851722

 

Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome

Abstract:

BACKGROUND: There is a growing body of evidence supporting the theory that problems with immune function play an important role in chronic fatigue syndrome (CFS).

METHODS: We studied 90 CFS cases and 50 healthy controls from two different areas of upstate New York to determine whether there were differences in the absolute number and pattern of natural killer (NK) and cytotoxic T-cell phenotypes between CFS cases and healthy controls in the two regions. One group was from a small town where a cluster of cases existed; the other was from a large metropolitan area where there was not a known cluster.

RESULTS: The number of CD56+CD3+CD8+ and CD56+CD3+CD8- cells in cases from the two areas were both significantly elevated over that of controls from the metropolitan area (P < 0.03). The number of CD56+CD3-CD8+ and CD56+CD3-CD8- cells was significantly reduced in the two case groups compared to that of controls from the metropolitan area (P = 0.04). However, controls who were from the same town as the cluster cases had numbers of CD56+CD3+CD8+, CD56+CD3+CD8-, and CD56+CD3-CD8- cells that were more like that of cases than controls. Only the number of CD56+CD3-CD8+ cells (an NK cell subset) was significantly different in cases versus controls from the cluster area (P = 0.022).

CONCLUSIONS: These data suggest that differences in controls from cluster and noncluster areas may be responsible for some of the inconsistencies in results from other studies. Furthermore, they suggest the possibility that NK cell function may play an important role in preventing the development of CFS in individuals who live in a community where a cluster of cases have been identified.

Copyright 2003 Wiley-Liss, Inc.

 

Source: Stewart CC, Cookfair DL, Hovey KM, Wende KE, Bell DS, Warner CL. Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome. Cytometry B Clin Cytom. 2003 May;53(1):26-33. http://onlinelibrary.wiley.com/doi/10.1002/cyto.b.10034/full  (Full article)

 

Normal production of inflammatory cytokines in chronic fatigue and fibromyalgia syndromes determined by intracellular cytokine staining in short-term cultured blood mononuclear cells

Abstract:

It has been proposed that cytokines play a role in the pathogenesis of chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS). However, different studies have reported conflicting results using enzyme-linked immunosorbent assay or polymerase chain reaction to detect cytokines in these conditions.

In the present study, for the first time, the production of inflammatory [interleukin (IL)-1alpha, IL-6, and TNF-alpha] and anti-inflammatory (IL-10) cytokines by CD14+ and CD14- peripheral blood mononuclear cells (PBMC) from chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS) patients and sex- and age-matched normal subjects was investigated at the level of individual cells using the technique of intracellular cytokine staining and flow cytometry. Cultures were carried out in the presence of polymyxin B to inhibit the effect of endotoxins on cytokine production by monocytes.

The mean intensity of fluorescence (MIF) and percentage of CD14+ (monocytes) and CD14- (lymphocytes) cytokine-producing mononuclear cells were comparable in patients and controls in either unstimulated or IFN-gamma-stimulated conditions. Our study indicates that dysregulation of cytokine production by circulating monocytes or non-monocytic cells (lymphocytes) is not a dominant factor in the pathogenesis of CFS/FMS.

 

Source: Amel Kashipaz MR, Swinden D, Todd I, Powell RJ. Normal production of inflammatory cytokines in chronic fatigue and fibromyalgia syndromes determined by intracellular cytokine staining in short-term cultured blood mononuclear cells. Clin Exp Immunol. 2003 May;132(2):360-5. http://www.ncbi.nlm.nih.gov/pubmed/12699429

 

Immunological anomalies and thrombocytopenia in 117 dogs and cats diagnosed with chronic fatigue syndrome (CFS)

Abstract:

Retrospective analysis of immune dysfunctions found in 55 dogs and 62 cats diagnosed with Chronic Fatigue Syndrome (CFS), revealed leukopenia in 11% of dogs (n = 6) and 22.5% of cats (n = 14), lymphopenia in 14.5% of dogs (n = 8) and 10% of cats (n = 6), hypogammaglobulinaemia in 9% of dogs (n = 5) and 13% of cats (n = 8) and thrombocytopenia in 20% of dogs (n = 11) and 68% of cats (n = 42). All patients had creatine kinase enzyme levels above the normal range (CK = 5-100 IU/L) and carried micrococcus-like organisms on erythrocytes.

Blood cultures proved positive for Staphylococcus spp. in 16 cases. After low-dosage arsenic-based therapy (thiacetarsamide sodium) all animals experienced complete clinical remission. Subsequent controls demonstrated immune restoration in 4 representative FIV-FeLV negative cats, previously diagnosed with CFS associated with leukopenia, lymphopenia, hypogammaglobulinaemia and thrombocytopenia.

The main conclusion is that a CFS-like disease in dogs and cats, characterised by the common hallmarks of high CK levels, absence of known causes of chronic fatigue in animals and presence of micrococcus-like organisms in the blood, can be associated with humoral and/or cellular immune deficiencies in 9-22.5% of cases and with thrombocytopenia in 20-68% of cases. Considerations are made on the possible role of micrococci in the aetiology of the condition and on the similarities with CFS in humans.

 

Source: Tarello W. Immunological anomalies and thrombocytopenia in 117 dogs and cats diagnosed with chronic fatigue syndrome (CFS). Acta Vet Hung. 2003;51(1):61-72. http://www.ncbi.nlm.nih.gov/pubmed/12688127