Chronic fatigue syndrome (CFS) is an illness characterized by unexplained and prolonged fatigue that is often accompanied by abnormalities of immune, endocrine and cognitive functions. Diminished natural killer cell cytotoxicity (NKCC) is a frequently reported finding. However, the molecular basis of this defect of in vitro cytotoxicy has not been described. Perforin is a protein found within intracellular granules of NK and cytotoxic T cells and is a key factor in the lytic processes mediated by these cells. Quantitative fluorescence flow cytometry was used to the intracellular perforin content in CFS subjects and healthy controls. A significant reduction in the NK cell associated perforin levels in samples from CFS patients, compared to healthy controls, was observed. There was also an indication of a reduced perforin level within the cytotoxic T cells of CFS subjects, providing the first evidence, to our knowledge, to suggest a T cell associated cytotoxic deficit in CFS. Because perforin is important in immune surveillance and homeostasis of the immune system, its deficiency may prove to be an important factor in the pathogenesis of CFS and its analysis may prove useful as a biomarker in the study of CFS.
Epstein-Barr virus (EBV) has long been discussed as a possible cause or trigger of Chronic Fatigue Syndrome (CFS). In a subset of patients the disease starts with infectious mononucleosis and both enhanced and diminished EBV-specific antibody titers have been reported. In this study, we comprehensively analyzed the EBV-specific memory B- and T-cell response in patients with CFS. While we observed no difference in viral capsid antigen (VCA)-IgG antibodies, EBV nuclear antigen (EBNA)-IgG titers were low or absent in 10% of CFS patients. Remarkably, when analyzing the EBV-specific memory B-cell reservoir in vitro a diminished or absent number of EBNA-1- and VCA-antibody secreting cells was found in up to 76% of patients. Moreover, the ex vivo EBV-induced secretion of TNF-α and IFN-γ was significantly lower in patients. Multicolor flow cytometry revealed that the frequencies of EBNA-1-specific triple TNF-α/IFN-γ/IL-2 producing CD4+ and CD8+ T-cell subsets were significantly diminished whereas no difference could be detected for HCMV-specific T-cell responses. When comparing EBV load in blood immune cells, we found more frequently EBER-DNA but not BZLF-1 RNA in CFS patients compared to healthy controls suggesting more frequent latent replication. Taken together, our findings give evidence for a deficient EBV-specific B- and T-cell memory response in CFS patients and suggest an impaired ability to control early steps of EBV reactivation. In addition the diminished EBV response might be suitable to develop diagnostic marker in CFS.
CFS individuals analyzed in this study show no differences in B-cell compartment, skewed NK cells and poorly responsive T cells.
The observed immunological defaults do not provide any causative link to the illness, but could explain some of the symptoms and in particular the poor control of viral infections reported in these individuals. Some of these biomarkers may be useful for the characterization of CFS. (But you have to distinguiesh between ME, CFS ,or both).
Abstract Myalgic encephalomyelitis (ME, also called Chronic Fatigue Syndrome), a common disease with chronic fatigability, cognitive dysfunction and myalgia of unknown etiology, often starts with an infection. The chaperonin human heat shock protein 60 (HSP60) occurs in mitochondria and in bacteria, is highly conserved, antigenic and a major autoantigen. The anti-HSP60 humoral (IgG and IgM)…
The cytokine (IFN-γ, IL-6, IL-8, IL-10, MIP-1β , MCP-1, and MIP1-α ) responses to mitogenic activators of PBMC isolated from patients with FM were significantly lower than those of healthy individuals, implying that cell-mediated immunity is impaired in FM patients. This research resulted in a diagnostic test for fibromyalgia.
Researchers found that both CFS/fibromyalgia patients have low Coenzyme Q10 levels and low ATP levels, and increased levels of lipid peroxidation (which is an indicator for damage caused by oxidative stress).
In addition fibromyalgia patients had low levels of two mitochondrial enzymes and a mitochondrial protein, and reduced levels of mitochondrial DNA content, while all of those were normal in CFS patients. Therefor mitochondrial dysfunction-dependent events could be a biomarker to distinguish between FM and CFS.
Researchers were able to differentiate patients with FM from those with osteoarthritis (OA) and rheumatoid arthritis (RA), and to identify molecular species associated with the spectral patterns.
They demonstrated the ability of IRMS to achieve reliable resolution of unique spectral patterns specific to FM.
Metabolomic analysis revealed that RA and OA groups were metabolically similar, whereas biochemical differences were identified in the FM that were quite distinctive from those found in the other two groups.
– braine whitespots/lesions. increased T2-signal lesions.
– spinal tap, elevated proteins for 30%
– some researchers would label ALL patients with somatization, but in reality there are physiological processes responsible for symptoms.
– patients without any co-morbid psychiatric/psychological disorders had high % or physiological abnormalities
– orthostatic intolerance , also in relation to hyperventilation
Mentions Infection hypothesis, Oxidative Stress hypothesis, Free Radicals Hypothesis. (see also Possible causes
They tested 21 patients, 21 healthy employees, and 42 people that lived in the same area as the 21 patients.
The HTLV-II gag gene was not found in the bloodsamples, it is not a suitable biomarker.