Evidence browser

Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case-control study.

Clark, L V, Buckland, M, Murphy, G et al.·Clinical and experimental immunology·2017

This study examined whether people with ME/CFS have abnormal immune protein levels (cytokines) in their blood, especially after physical activity. Researchers compared 24 ME/CFS patients with 21 healthy controls and measured multiple immune markers at rest and after exercise. The study found no significant differences in immune protein levels between the two groups, and no link between post-exertional symptoms and increased cytokine levels.

E2 ModerateCommentaryPEM unclearCommentary

Support for the microgenderome invites enquiry into sex differences.

Wallis, Amy, Butt, Henry, Ball, Michelle et al.·Gut microbes·2017

This study looked at how gut bacteria, sex hormones, and the immune system interact differently in men and women with ME/CFS. The researchers found that the relationship between specific types of bacteria in the gut and ME/CFS symptoms varies between males and females. This suggests that biological sex may play an important role in how the microbiome affects ME/CFS symptoms.

Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology.

Halpin, Peter, Williams, Marshall Vance, Klimas, Nancy G et al.·Journal of medical virology·2017

This study looked at whether people with ME/CFS and Gulf War Illness have unusual immune responses to certain viruses, particularly Epstein-Barr virus, HHV-6, and varicella-zoster virus. Researchers found that people with these conditions are more likely than healthy people to produce antibodies (immune proteins) against proteins made by these viruses. These antibody patterns might eventually help doctors identify and diagnose these illnesses more accurately.

E2 ModeratePEM unclearBiobank-Resource

The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis.

Lacerda, Eliana M, Bowman, Erinna W, Cliff, Jacqueline M et al.·Open journal of bioresources·2017

The UK ME/CFS Biobank is a collection of blood samples and health information from 284 people with ME/CFS, 60 people with multiple sclerosis, and 135 healthy volunteers. Researchers created this resource to help scientists study what causes ME/CFS and find better ways to diagnose and treat it. The samples and detailed patient information can be used by researchers worldwide to search for biological markers of the disease.

BiomarkersImmune System

E2 ModerateCohortPEM not requiredCross-Sectional

Transforming growth factor beta (TGF-β) in adolescent chronic fatigue syndrome.

Wyller, Vegard Bruun, Nguyen, Chinh Bkrong, Ludviksen, Judith Anita et al.·Journal of translational medicine·2017

This study tested whether a protein called TGF-β, which helps regulate immune and stress responses, was elevated in adolescents with ME/CFS. Researchers compared blood levels of TGF-β in 120 young ME/CFS patients to 68 healthy controls and found the protein levels were actually the same in both groups. However, they discovered that in ME/CFS patients, TGF-β levels were connected to stress hormones and fatigue severity, suggesting it may play a role in how the illness affects the body even if it's not simply 'too high.'

Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women.

Milrad, Sara F, Hall, Daniel L, Jutagir, Devika R et al.·Journal of neuroimmunology·2017

This study looked at 60 women with ME/CFS to understand how sleep quality affects their symptoms and inflammation levels. Researchers found that women who slept poorly had higher levels of inflammatory substances in their blood and experienced more severe fatigue and ME/CFS symptoms. The findings suggest that improving sleep quality might help reduce both inflammation and symptom severity in people living with ME/CFS.

E2 ModerateCohortPEM not requiredCross-Sectional

Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival.

Nguyen, Chinh Bkrong, Alsøe, Lene, Lindvall, Jessica M et al.·Journal of translational medicine·2017

This study looked at blood samples from 29 teenagers with ME/CFS and compared them to 18 healthy teens to see if their genes were working differently. The researchers found that certain immune cells involved in fighting infection were not developing or surviving normally in the ME/CFS group, and that signs of inflammation and antiviral activity were higher. These gene changes were connected to nervous system problems and symptoms like post-exertional malaise (feeling much worse after activity).

RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell/T-Cell Receptor Signatures in Complex Chronic Disease.

Bouquet, Jerome, Gardy, Jennifer L, Brown, Scott et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·2017

Researchers used genetic testing to compare blood samples from people with ME/CFS and a similar condition called alternative Lyme disease to healthy controls and people with lupus. They looked for differences in gene activity, immune cell patterns, and viral infections. Surprisingly, they found no major differences in gene activity between ME/CFS patients and healthy people, though they did find differences in lupus patients as expected.

Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients.

Theorell, Jakob, Bileviciute-Ljungar, Indre, Tesi, Bianca et al.·Frontiers in immunology·2017

Researchers tested whether immune cells called cytotoxic lymphocytes—which normally fight infections and respond to stress—work differently in ME/CFS patients compared to healthy people. They studied 48 ME/CFS patients and found that these immune cells looked and functioned normally, suggesting they are not responsible for ME/CFS symptoms. This means cytotoxic lymphocytes alone cannot be used as a simple blood test to diagnose the condition.

Giardia-specific cellular immune responses in post-giardiasis chronic fatigue syndrome.

Hanevik, Kurt, Kristoffersen, Einar, Mørch, Kristine et al.·BMC immunology·2017

Researchers studied whether people who developed ME/CFS after a Giardia infection (a parasite that causes stomach illness) had different immune responses compared to those who recovered. They found that fatigued patients had higher levels of a specific immune protein called sCD40L, which correlated with how tired they felt. However, most immune markers tested were similar between those who developed ME/CFS and those who recovered, suggesting the answer may be more complex than initially expected.

E2 ModerateCohortPEM requiredCross-Sectional

Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study.

Lidbury, Brett A, Kita, Badia, Lewis, Donald P et al.·Journal of translational medicine·2017

Researchers tested blood samples from people with ME/CFS and compared them to healthy controls, looking for differences in proteins called activins. They found that people with ME/CFS had significantly higher levels of a protein called activin B, while activin A remained normal. This pattern could potentially be used as a blood test to help diagnose ME/CFS, since currently there is no reliable diagnostic test available.

E2 ModerateCohortPEM requiredObservational

Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients.

Nguyen, Thao, Johnston, Samantha, Chacko, Anu et al.·Asian Pacific journal of allergy and immunology·2017

This study looked at immune cells called mast cells in the blood of people with ME/CFS and compared them to healthy people. Researchers found that ME/CFS patients—especially those with severe illness—had more mast cells and these cells showed different activation patterns. Mast cells are known to release chemicals that cause inflammation, so understanding them better could help explain some ME/CFS symptoms.

Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations.

Hornig, M, Gottschalk, C G, Eddy, M L et al.·Translational psychiatry·2017

This study examined fluid from around the brain and spinal cord in people with ME/CFS to look for immune system differences. Researchers found that people whose ME/CFS started differently (without a clear infection trigger) had different patterns of immune molecules compared to those with typical ME/CFS that started after a viral-like illness. The atypical group had lower levels of certain inflammatory markers and less coordinated immune activity in their central nervous system.

Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray.

Loebel, Madlen, Eckey, Maren, Sotzny, Franziska et al.·PloS one·2017

This study examined whether ME/CFS patients have different immune responses to Epstein-Barr virus (EBV), a common virus that can cause mononucleosis. Researchers compared antibody patterns in 92 ME/CFS patients versus 50 healthy people and found that ME/CFS patients had slightly higher antibody levels against a specific EBV protein called EBNA-6. This suggests that some ME/CFS patients may have an altered immune response to EBV, though most antibody patterns were similar between patients and healthy controls.

Impact of Rantes from jawbone on Chronic Fatigue Syndrome.

Lechner, J, Huesker, K, Von Baehr, V·Journal of biological regulators and homeostatic agents·2017

This study investigated whether inflammation in the jawbone might contribute to ME/CFS. Researchers compared jawbone tissue from 21 ME/CFS patients with tissue from 19 healthy people and found that ME/CFS patients had significantly higher levels of inflammatory proteins (RANTES and FGF-2) in areas of jawbone that had undergone incomplete healing. The authors suggest that this hidden jawbone inflammation might be a previously unknown trigger for ME/CFS.

E2 ModerateCohortPEM not requiredObservational

Current Safety Concerns with Human Papillomavirus Vaccine: A Cluster Analysis of Reports in VigiBase®.

Chandler, Rebecca E, Juhlin, Kristina, Fransson, Jonas et al.·Drug safety·2017

Researchers analyzed thousands of reports from a global database of side effects following HPV vaccination. They found that certain combinations of symptoms—headaches, dizziness, fatigue, and fainting—were reported more often after HPV vaccination than with other vaccines, particularly in young women. These symptom clusters resemble conditions like POTS, CRPS, and chronic fatigue syndrome, though most reports did not include an official diagnosis.

E2 ModerateCohortPEM not requiredCross-Sectional

Physio-somatic symptoms in schizophrenia: association with depression, anxiety, neurocognitive deficits and the tryptophan catabolite pathway.

Kanchanatawan, Buranee, Sirivichayakul, Sunee, Thika, Supaksorn et al.·Metabolic brain disease·2017

This study looked at physical symptoms like fatigue, muscle pain, and flu-like feelings in people with schizophrenia. Researchers found that more than half of schizophrenia patients experienced these symptoms, which were linked to depression, anxiety, and problems with memory and attention. The symptoms appeared to be connected to changes in how the body processes tryptophan, an amino acid, and how the immune system responds to these breakdown products.

E2 ModerateMechanismPEM unclearMechanistic

Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome.

Loebel, Madlen, Grabowski, Patricia, Heidecke, Harald et al.·Brain, behavior, and immunity·2016

Researchers tested whether ME/CFS patients have unusually high levels of antibodies (immune proteins) that attack nerve signaling receptors in the body. They found that about 30% of ME/CFS patients had elevated antibodies against certain receptors involved in adrenaline and acetylcholine signaling—chemicals that control heart rate, breathing, and other automatic body functions. Importantly, patients who received rituximab (a treatment that depletes B cells) and improved showed decreases in these antibody levels, suggesting a possible link between these antibodies and disease activity.

BiomarkersImmune System

E2 ModerateCohortPEM unclearCase-Control

Illness progression in chronic fatigue syndrome: a shifting immune baseline.

Russell, Lindsey, Broderick, Gordon, Taylor, Renee et al.·BMC immunology·2016

This study looked at three inflammatory proteins (IL-1α, IL-6, and IL-8) in the blood of people with ME/CFS at different stages of illness—newly diagnosed teenagers, people in the middle of their illness, and those who had been sick for over a decade. The researchers found that the pattern of these proteins changes as the illness progresses, suggesting that the body's immune response shifts over time. By adjusting for how long someone has been ill, doctors might be able to use these three proteins together to identify ME/CFS with 75-88% accuracy.

BiomarkersImmune System

Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome.

Schlauch, K A, Khaiboullina, S F, De Meirleir, K L et al.·Translational psychiatry·2016

Researchers compared the genes of people with ME/CFS to healthy people and found 442 genetic differences that may be linked to the condition. While most of these differences were in non-coding parts of the genome, some were in actual genes that produce proteins, including two that change how proteins work. Some genetic differences were found in genes related to the immune system's T-cells, which fight infection.