Decreased expression of CD69 in chronic fatigue syndrome in relation to inflammatory markers: evidence for a severe disorder in the early activation of T lymphocytes and natural killer cells.
ABSTRACT There is some evidence that patients with chronic fatigue syndrome (CFS) suffer from immune abnormalities, such as immune activation and decreased immune cell responsivity upon polyclonal stimili. This study was designed to evaluate lymphocyte activation in CFS by using a CD69 expression assay. CD69 acts as a costimulatory molecule for T- and natural killer (NK) cell activation. We collected whole blood from CFS patients, who met CDC criteria, and healthy volunteers. The blood samples were stimulated with mitogens during 18 h and the levels of activated T and NK cells expressing CD69 were measured on a Coulter Epics flow cytometer using a three color immunofluorescence staining protocol. The expression of the CD69 activation marker on T cells (CD3+, CD3+CD4+, and CD3+CD8+) and on NK cells (CD45+CD56+) was significantly lower in CFS patients than in healthy subjects. These differences were significant to the extent that a significant diagnostic performance was obtained, i.e. the area under the ROC curve was around 89%. No differences either in the number of leukocytes or in the number or percentage of lymphocytes, i.e. CD3, CD4, CD8 and CD19, could be found between CFS patients and the controls. Patients with CFS show defects in T- and NK cell activation. Since induction of CD69 surface expression is dependent on the activation of the protein kinase C (PKC) activation pathway, it is suggested that in CFS there is a disorder in the early activation of the immune system involving PKC.
SourceAvailable from: Nancy G Klimas
Article: Human freedom and the brain.[Show abstract] [Hide abstract]
ABSTRACT: Freedom of will does exist, it is self-leadership of man based on reason and ethos. Evidence comes from truth. Determinism cannot be proved since if you try, you mean to prove a truth; but there is no truth without freedom. By contrast for freedom there are many pieces of evidence e.g. science, arts, technology. Freedom utilizes creative abstract thinking with phantasy. Freedom is graded, limited, based on nature, but not developed without good will. We perceive reliably freedom by self-consciousness and in other persons as long as we are sober. Freedom needs intelligence, but is more, it is a creative and moral virtue. The basis for freedom is phylogenesis and culture, in the individual learning and experimenting. Factors in the becoming of freedom are not only genes and environment but also self-discipline. But the creativity of free will is dangerous. Man therefore needs morale. Drives and feelings become humanized, cultural interests are developed. There is a humane nobility from long good will.Acta Neuropsychiatrica 06/2009; 21 Suppl 2:1-6. DOI:10.1111/j.1601-5215.2009.00386.x · 0.64 Impact Factor
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ABSTRACT: Many patients with myalgic encephalopathy (fibromyalgia/chronic fatigue syndrome) localise the beginning of their disease at a time period of emotional, or professional, or social stress, or an infectious or traumatic/surgical incident. It is suggested that these may have temporarily suppressed their immunological system, after which a "rebound" of hyper-immunity has occurred. Hyper-immunity against external aggressors is commonly characterized by an extremely high titre of Immunolobulin G against the Epstein-Barr virus (Herpes 4), or elevated Anti-Streptolysin-O titre (ASLO). In a proportion of patients, hyper-immunity proceeds to auto-immunity with IgG antibodies against the thyroid gland (Hashimoto's disease), Antinuclear antibodies (ANF or ANA), and sometimes positive rheumatism-tests. The IgG covalently binds to Complement C3, which complex is cytotoxic by damaging the cell membrane, and induces inflammation. Simultaneously large quantities of reactive oxygen species (ROS) are produced. This causes muscular pain, poor energy production by the mitochondria, and increased permeability of the capillary vessels, also in the brain. The latter disturbs the thalamo-hypothalamo-pituitary regulation, impairs cognitive function, mood and the working memory. It disturbs the nycthemeral rhythm and the sleep pattern, and may cause neuro-vegetative dysfunction. Antibodies against the myelin sheet as well as impaired neurotransmission may be involved in polyneuropathy. Conventional treatment must correct possible endocrine deficiencies and can help alleviating particular symptoms. Causal treatment addresses the immune dysfunction using corticosteroids, gamma globulin infusions, or immune-suppressors. Immune modulators can selectively be attempted. However, treatment should also address the pathogenic mechanisms by prescribing an appropriate diet, and particular food supplements (Complementary and Alternative Medicine, CAM). We have developed a * Frank@comhaire.com; Brakelmeersstraat, 18; B 9830 Sint Martens-Latem; Belgium. Frank H. Comhaire 2 specific nutraceutical containing several anti-oxidants (Astaxanthin, Oxido-reductase ubiquinone Q10), a strong natural anti-inflammatory substance (pine bark extract, Pycnogenol®), the fyto-adaptogen Lepidium meyenii (MACA), acetyl-carnitine, zinc, and vitamins B6, B9 and B12. To this supplement long-chain poly-unsaturated omega-3 fatty acids are added (docosahexaenoic acid, DHA, and eicosapentaenoic acid, EPA). The CAM approach induces and maintains improvement in 85% of patients, but it seldom results in the complete disappearance of signs and symptoms.