Evidence browser

Predictors of Fatigue among Patients with Chronic Fatigue Syndrome.

Jason, Leonard A, Brown, Molly, Evans, Meredyth et al.·Journal Of Human Behavior In The Social Environment·2012

This study asked ME/CFS patients to keep detailed activity logs to understand what triggers their fatigue. Researchers looked at what patients were doing, what they had been doing 30 minutes earlier, and their fatigue levels to find patterns. The study suggests that tracking daily activities can help doctors and patients see which activities are most connected to fatigue flare-ups.

Activation of cell-mediated immunity in depression: association with inflammation, melancholia, clinical staging and the fatigue and somatic symptom cluster of depression.

Maes, Michael, Mihaylova, Ivana, Kubera, Marta et al.·Progress in neuro-psychopharmacology & biological psychiatry·2012

This study looked at immune system markers in people with depression, comparing them to healthy controls. Researchers measured chemicals called neopterin and inflammatory proteins in the blood and found they were higher in depressed patients, especially those with melancholia (severe depression with physical symptoms). These same markers were also linked to chronic fatigue symptoms, suggesting that immune system activation may play a role in both depression and fatigue.

Heterogeneous nuclear RNPs as targets of autoantibodies in systemic rheumatic diseases.

Op De Beéck, Katrijn, Maes, Liesbeth, Van den Bergh, Karolien et al.·Arthritis and rheumatism·2012

This study looked for specific autoantibodies (immune proteins that attack the body's own cells) in people with various rheumatic diseases, including those with chronic fatigue syndrome. Researchers tested blood samples from hundreds of patients and healthy controls, measuring antibodies against different protein targets called hnRNPs. They found that people with Sjögren's syndrome (an autoimmune disease affecting glands) had significantly more of these antibodies compared to healthy people.

E2 ModerateCohortPEM unclearCase-Control

IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression.

Maes, Michael, Mihaylova, Ivana, Kubera, Marta et al.·Metabolic brain disease·2012

This study examined immune system markers in people with ME/CFS, depression, and healthy controls. Researchers found that people with ME/CFS had higher levels of specific immune antibodies (IgM) attacking certain body molecules compared to people with depression. These antibodies were especially high against fatty acid anchors and oxidatively damaged proteins, suggesting ME/CFS may involve distinct immune processes that differ from depression.

E2 ModerateCohortPEM not requiredCase-Control

Excess of activating killer cell immunoglobulin‑like receptors and lack of HLA-Bw4 ligands: a two‑edged weapon in chronic fatigue syndrome.

Pasi, Annamaria, Bozzini, Sara, Carlo-Stella, Nicoletta et al.·Molecular medicine reports·2011

This study examined immune system genes called KIRs and their matching partners (HLA molecules) in people with ME/CFS. Researchers found that people with ME/CFS had an unusual pattern of these immune genes—specifically, more of a type called KIR3DS1 and fewer matching HLA partners for their receptors to recognize. The researchers suggest this mismatch might make it harder for the immune system to fight off infections, potentially allowing chronic infections to persist.

Xenotropic murine leukemia virus-related virus-associated chronic fatigue syndrome reveals a distinct inflammatory signature.

Lombardi, Vincent C, Hagen, Kathryn S, Hunter, Kenneth W et al.·In vivo (Athens, Greece)·2011

This 2011 study looked for a specific virus (XMRV) in the blood of ME/CFS patients and measured immune system chemicals called cytokines and chemokines. Researchers found a distinctive pattern of 10 immune chemicals that could identify XMRV-positive patients with very high accuracy (93-96%), suggesting that this virus may trigger a particular type of immune response in some people with ME/CFS.

E2 ModerateCohortPEM unclearCross-Sectional

Diagnostic accuracy of symptoms characterising chronic fatigue syndrome.

Davenport, Todd E, Stevens, Staci R, Baroni, Katie et al.·Disability and rehabilitation·2011

This study looked at which symptoms best identify people with ME/CFS by comparing 16 patients with the condition to 14 healthy controls. The researchers found that failure to recover within one day after intense exercise was the strongest single indicator of ME/CFS, and combining three symptoms—immune problems, sleep disturbance, and pain—could accurately identify most patients. The findings suggest that fewer symptoms may be needed to diagnose ME/CFS than current guidelines require.

Immune SystemPost-Exertional Malaise

E2 ModerateCohortPEM unclearCase-Control

An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue.

Sullivan, Patrick F, Allander, Tobias, Lysholm, Fredrik et al.·BMC microbiology·2011

Researchers used advanced genetic sequencing to search for viruses in the blood of 45 people with chronic fatigue syndrome, comparing each patient to their identical twin who did not have the illness. They found that a virus called GB virus C appeared in a few patients but not in their healthy twins, suggesting it might be linked to ME/CFS. However, the overall results did not strongly support the idea that a single detectable virus causes chronic fatigue.

E2 ModerateCohortPEM unclearCase-Control

Investigation into the presence of and serological response to XMRV in CFS patients.

Erlwein, Otto, Robinson, Mark J, Kaye, Steve et al.·PloS one·2011

This study tested whether a virus called XMRV could be found in people with ME/CFS. Researchers used the same methods from earlier studies that had suggested a link between this virus and ME/CFS. They checked patient blood samples for the virus itself and for antibodies (immune response markers) to the virus. Their results found no evidence that XMRV is associated with ME/CFS in UK patients.

Detection of antinuclear antibodies by indirect immunofluorescence and by solid phase assay.

Op De Beeck, Katrijn, Vermeersch, Pieter, Verschueren, Patrick et al.·Autoimmunity reviews·2011

This study compared two different blood tests for detecting antinuclear antibodies (proteins the immune system sometimes makes against the body's own cells). Researchers tested these methods in people with autoimmune diseases, healthy people, ME/CFS patients, and other disease controls. The newer solid phase test was better at correctly identifying people with certain autoimmune diseases, though both tests rarely showed false positives in ME/CFS patients.

E2 ModerateCohortPEM unclearCross-Sectional

Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Brenu, Ekua W, van Driel, Mieke L, Staines, Don R et al.·Journal of translational medicine·2011

This study examined immune system markers in 95 ME/CFS patients compared to 50 healthy people to see if certain blood tests could help diagnose the condition. Researchers found that ME/CFS patients had imbalanced immune responses, including higher levels of certain inflammatory proteins and lower activity of immune cells that normally fight infections. These immune differences might one day be used as reliable diagnostic markers to help doctors identify ME/CFS.

BiomarkersImmune System

E2 ModerateBehavioralPEM not requiredLongitudinal

Fatigue, depressive symptoms, and anxiety from adolescence up to young adulthood: a longitudinal study.

ter Wolbeek, Maike, van Doornen, Lorenz J P, Kavelaars, Annemieke et al.·Brain, behavior, and immunity·2011

This study followed 633 teenage girls for 4.5 years to understand what causes fatigue and ME/CFS-like symptoms in young adulthood. Researchers found that fatigue, depression, and anxiety tend to rise and fall together over time, and that certain immune markers and emotional problems during teenage years could predict who would develop fatigue later. The study suggests that warning signs of future fatigue can sometimes be spotted years before symptoms become serious.

Up-regulation of TGF-β1 mRNA expression in peripheral blood mononuclear cells of patients with chronic fatigue syndrome.

Zhang, Hai-Ying, Liu, Zhan-Dong, Hu, Chao-Jun et al.·Journal of the Formosan Medical Association = Taiwan yi zhi·2011

Researchers measured levels of a immune signaling molecule called TGF-β1 in blood cells from ME/CFS patients and compared them to healthy people and patients with other illnesses. They found that ME/CFS patients had significantly higher levels of TGF-β1 than both groups, suggesting this molecule may play a role in ME/CFS disease development.

IgM-mediated autoimmune responses directed against multiple neoepitopes in depression: new pathways that underpin the inflammatory and neuroprogressive pathophysiology.

Maes, Michael, Mihaylova, Ivana, Kubera, Marta et al.·Journal of affective disorders·2011

This study looked at whether depression involves the immune system attacking the body's own molecules that have been damaged by stress and inflammation. Researchers compared antibody levels in 26 depressed patients and 17 healthy controls, finding that depressed patients had significantly higher levels of immune proteins attacking several molecular targets. These autoimmune responses were linked to fatigue and flu-like symptoms, suggesting a biological pathway that may connect depression, immune dysfunction, and physical exhaustion.

E2 ModerateTrialPEM requiredObservational

Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome

Øystein Fluge, Olav Mella, Ove Bruland et al.·PLoS ONE·2011·n=30

In this pilot RCT, 30 ME/CFS patients received rituximab (a B-cell depleting antibody used in cancer and autoimmune disease) or placebo. Two-thirds of the rituximab group showed clinical improvement, with delayed response patterns consistent with autoimmune disease mechanisms. The placebo group had minimal response.

InterventionsImmune System

Peripheral blood gene expression in postinfective fatigue syndrome following from three different triggering infections.

Galbraith, Sally, Cameron, Barbara, Li, Hui et al.·The Journal of infectious diseases·2011

Researchers studied blood samples from 18 people who developed long-lasting fatigue after three different infections (Epstein-Barr virus, Ross River virus, and Q fever) and compared them to 18 healthy people who recovered normally. They looked for patterns in which genes were turned on or off that might explain the fatigue syndrome. While they found some differences in gene activity, these patterns were not consistent across the different infection groups, suggesting there may not be a single blood-based marker that identifies post-infectious fatigue.

E2 ModerateCohortPEM not requiredCase-Control

Immunologic and psychosocial status in chronic fatigue syndrome.

Nas, K, Cevik, R, Batum, S et al.·Bratislavske lekarske listy·2011

Researchers compared immune system markers and psychological health in 25 ME/CFS patients and 20 healthy controls. They found that ME/CFS patients had lower levels of a specific type of immune cell (CD56) and higher levels of an inflammatory marker (IL-6), along with more depression and reduced quality of life. These immune changes appeared connected to sleep problems, social isolation, and physical limitations.

Serological and virological investigation of the role of the herpesviruses EBV, CMV and HHV-6 in post-infective fatigue syndrome.

Cameron, Barbara, Flamand, Louis, Juwana, Hedy et al.·Journal of medical virology·2010

Researchers tested blood samples from ME/CFS patients and healthy controls to see whether three common herpesviruses (EBV, CMV, and HHV-6) were actively reactivating or causing ongoing infection. They found no evidence that these viruses were actively infected or reactivating in ME/CFS patients compared to controls who recovered normally from infection.

Xenotropic murine leukemia virus-related virus prevalence in patients with chronic fatigue syndrome or chronic immunomodulatory conditions.

Henrich, Timothy J, Li, Jonathan Z, Felsenstein, Donna et al.·The Journal of infectious diseases·2010

Researchers tested whether a virus called XMRV was present in people with ME/CFS and other conditions affecting the immune system. They collected samples from 293 patients, including 32 with ME/CFS, and looked for XMRV DNA. They found no evidence of this virus in any of the samples tested.