Blood Interferon – Chronic Fatigue Syndrome
A study published in the February issue of the new journal Science Advances is perhaps the first to identify distinct stages of chronic fatigue syndrome (CFS). Importantly, it demonstrates some immune signatures early in the course of CFS that are not present in subjects with longer duration of illness.
Chronic fatigue syndrome is a disabling disorder with complex features that can include fatigue, memory and concentration deficits, sleep disturbances, headache, joint and muscle pain, postexertional malaise, and gastrointestinal and immune system dysfunction, lasting for 6 months or more.
The diagnosis of CFS is largely based on recognition of signs and symptoms by experienced clinicians. Although laboratory assays play a role in the diagnostic process, they are used to rule out other conditions that can mimic aspects of CFS, rather than as biomarkers to facilitate early diagnosis. Efforts to identify immune biomarkers in CFS have produced inconsistent result.
Although efforts were made to identify a specific biological pattern, there are no trustful biomarkers or validated laboratory test for the diagnosis or management of CSF.
In an attempt to discover reliable biological markers related to chronic fatigue syndrome, Mady Hornig and colleagues from the Center for Infection and Immunity at the Columbia University’s Mailman School of Public Health, New York, USA determined the levels of 51 cytokines and chemokines in chronic fatigue syndrome patients from two large multicenter studies.
This is the first study to demonstrate altered plasma immune signatures early in the course of chronic fatigue syndrome that are not present in subjects with longer duration of illness.
In the Science Advances study these authors reported specific cytokine patterns during the early phase (≤3 years) of CSF, including high plasma levels of IL-1α, IL-1RA, IL-4, IL-8, IL-12p40, IL-13, IL-17A, TNF-α and MCP1. Of particular interest was the marked association of interferon (IFN)-γ with the early phase of illness that was detected through logistic regression modeling.
IFNγ is a product of activated T cells [particularly CD8+ and CD4+ T helper 1 (TH1) cells], natural killer cells, as well as activated macrophages in the periphery and microglia in the central nervous system. Some studies in CFS, but not all, have found plasma levels of IFNγ to be elevated, with effects restricted to males in one study.
IFNγ may accelerate degradation of tryptophan, resulting in depletion of the neurotransmitters serotonin and melatonin in the central nervous system through activation of indoleamine-2,3-dioxygenase, a rate-limiting enzyme in the kynurenine pathway. Activation of this pathway also results in increased levels of quinolinic acid, a neurotoxic compound that acts as an agonist at glutamatergic [NMDA (N-methyl-d-aspartate)] receptors
Of note, IFN- γ is known to modulate brain’s neuronal activity, affecting mood, sleep, temperature regulation and the endocrine system. Also, high levels of IFN- γ can lead to depressive states and physical tiredness similar to the observed in CSF patients, due to the degradation of tryptophan and reducing brain levels of serotonin and melatonin (M Maes et al., 2007; AH Miller et al., 2013).
The Hornig et al. study is consistent with the hypothesis of a viral trigger of this condition and, as discussed by the Center for Infection and Immunity Website at Columbia University, it may also substantiate the idea that ME/CFS reflects an infectious ‘hit-and-run’event. Overall; the study indicates that CSF is an immunological and not a psychological disease.
Early in the course of CFS, as determined by this study, specific immune profiles may have important implications for early diagnosis. This may also suggest new therapeutic and immunomodulatory interventions, which in this condition may be transient or time-limited.
Source: Science Advances, 2015, 1, no1:e1400121. DOI: 10.1126/sciadv.140012
Read More: Science Advances
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