Evidence browser

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 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.

Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional study.

Mensah, F, Bansal, A, Berkovitz, S et al.·Clinical and experimental immunology·2016

Researchers compared immune cells called B cells in people with ME/CFS and healthy people using specialized lab tests. While they didn't find major differences in the most common B cell types, they did discover subtle changes in how B cells are marked and organized in ME/CFS patients, particularly an increase in certain markers on specific B cell subsets. These findings suggest B cells may function differently in ME/CFS and could help explain why some patients improve with a drug that targets B cells.

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.

Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis.

Ohanian, Diana, Brown, Abigail, Sunnquist, Madison et al.·Neurology (E-Cronicon)·2016

Researchers used a machine learning technique to compare self-reported symptoms in people with ME/CFS to those with multiple sclerosis (MS). They found that five symptoms—particularly flu-like symptoms and tender lymph nodes—were associated with ME/CFS rather than MS, and the computer model correctly distinguished between the two conditions 81% of the time. These early findings suggest that symptom patterns may help differentiate ME/CFS from MS, though the study design does not establish whether these symptoms cause the conditions or how they relate to underlying biology.

Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome.

Giloteaux, Ludovic, Goodrich, Julia K, Walters, William A et al.·Microbiome·2016

This study found that people with ME/CFS have different gut bacteria compared to healthy people. The bacteria in ME/CFS patients showed less diversity and included more potentially harmful species while having fewer beneficial ones. Additionally, researchers detected signs in the blood suggesting that bacteria or bacterial components may be leaking through the gut lining, which could contribute to inflammation and symptoms.

Association of biomarkers with health-related quality of life and history of stressors in myalgic encephalomyelitis/chronic fatigue syndrome patients.

Fenouillet, Emmanuel, Vigouroux, Aude, Steinberg, Jean Guillaume et al.·Journal of translational medicine·2016

This study examined blood markers and muscle function in 36 ME/CFS patients compared to 11 healthy controls to understand whether biological changes relate to symptoms and quality of life. Researchers found three key differences: problems with muscle response to exercise, increased oxidative stress (cellular damage), and changes in immune cells. These biomarkers correlated with how much ME/CFS affected patients' daily lives, especially in those whose illness started after a severe infection.

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.

Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome.

Hornig, M, Gottschalk, G, Peterson, D L et al.·Molecular psychiatry·2016

Researchers examined fluid from around the spine (cerebrospinal fluid) in ME/CFS patients and compared it to healthy people and those with multiple sclerosis. They found that ME/CFS patients had unusual patterns of immune proteins called cytokines in this fluid, suggesting their immune system in the brain and spinal cord is activated differently. The most notable finding was higher levels of a protein called eotaxin, which typically helps recruit immune cells involved in allergic responses.

Support for the Microgenderome: Associations in a Human Clinical Population.

Wallis, Amy, Butt, Henry, Ball, Michelle et al.·Scientific reports·2016

This study looked at gut bacteria in 274 ME/CFS patients and found that certain bacteria may affect symptoms differently in men and women, even when they have similar amounts of these bacteria. Specific bacteria called Firmicutes (including types like Clostridium and Lactobacillus) appeared connected to neurological, immune, and mood symptoms, but the way they affected symptoms depended on the patient's sex. This suggests that sex differences matter when understanding how gut bacteria influence ME/CFS.

E2 ModerateCohortPEM not requiredObservational

[The influence of physical load on the propriate immune and physiological parameters.].

Milicková, M, Zákovská, A, Chlíbková, D·Ceskoslovenska fysiologie·2016

This study looked at how intense physical exercise affects the immune system by measuring antibodies (immune proteins) in ultramarathon runners before and after a race. The researchers found that two types of antibodies—IgA and IgG—increased after the race, suggesting that extreme physical stress temporarily changes how the immune system works. Understanding these changes may help explain why some people develop chronic fatigue after intense exercise.

Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome.

Landi, Abdolamir, Broadhurst, David, Vernon, Suzanne D et al.·Cytokine·2016

Researchers measured 34 different immune system proteins in blood samples from 100 ME/CFS patients and 79 healthy controls. They found that three specific immune proteins—IL-16, IL-7, and VEGF-A—were significantly lower in ME/CFS patients. This pattern was different from what is seen in other chronic diseases with similar fatigue symptoms, suggesting it may be unique to ME/CFS.

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.

E2 ModerateMechanismPEM unclearMechanistic

ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56 dim CD16+ and CD56 bright CD16 dim/- natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients.

Huth, Teilah Kathryn, Staines, Donald, Marshall-Gradisnik, Sonya·Journal of translational medicine·2016

This study looked at natural killer (NK) cells, which are immune cells that help fight infections and abnormal cells. Researchers found that NK cells in ME/CFS patients have problems with their internal signaling systems—the chemical pathways that tell these cells to attack threats. Specifically, certain types of NK cells showed abnormal activity in proteins called ERK, MEK, and p38 when compared to healthy people. These problems in cell signaling might explain why people with ME/CFS have weaker immune responses.

A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis.

Brenu, Ekua W, Broadley, Simon, Nguyen, Thao et al.·Journal of immunology research·2016

This study compared immune cell markers (CD8+ T cells) in people with ME/CFS, people with multiple sclerosis (MS), and healthy controls. Researchers observed that certain protein markers on CD8+ T cells were altered in both ME/CFS and MS patients compared to controls, but this is a preliminary finding based on a small number of participants, and larger studies are needed to confirm whether these differences are meaningful.

Natural killer cells and single nucleotide polymorphisms of specific ion channels and receptor genes in myalgic encephalomyelitis/chronic fatigue syndrome.

Marshall-Gradisnik, Sonya, Huth, Teilah, Chacko, Anu et al.·The application of clinical genetics·2016

This study looked at immune cells called natural killer cells in ME/CFS patients and compared them to healthy controls. Researchers found that ME/CFS patients had weaker natural killer cell function and carried genetic variations in genes related to calcium regulation and nerve signal transmission. These genetic differences were not found in the healthy control group, suggesting they may play a role in ME/CFS.

E2 ModerateMechanismPEM unclearMechanistic

Single nucleotide polymorphisms and genotypes of transient receptor potential ion channel and acetylcholine receptor genes from isolated B lymphocytes in myalgic encephalomyelitis/chronic fatigue syndrome patients.

Marshall-Gradisnik, Sonya, Johnston, Samantha, Chacko, Anu et al.·The Journal of international medical research·2016

This small study looked at genetic differences in immune cells (B cells) from ME/CFS patients compared to healthy people. Researchers found that ME/CFS patients had more variations in genes controlling calcium flow and acetylcholine signaling—two processes important for immune cell communication. Some of these genetic variations were much more common in patients with ME/CFS, suggesting they might play a role in the disease.

Gene Expression Factor Analysis to Differentiate Pathways Linked to Fibromyalgia, Chronic Fatigue Syndrome, and Depression in a Diverse Patient Sample.

Iacob, Eli, Light, Alan R, Donaldson, Gary W et al.·Arthritis care & research·2016

Researchers studied blood cell genes from 261 people—including those with ME/CFS, fibromyalgia, depression, and healthy controls—to see if certain genes work together in patterns tied to these conditions. They found four distinct gene clusters, and two of these clusters showed opposite patterns in ME/CFS patients compared to those with depression, suggesting these conditions may involve different biological pathways even when they overlap.

Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison.

Ramos, Sandra, Brenu, Ekua, Broadley, Simon et al.·Asian Pacific journal of allergy and immunology·2016

This study compared immune system cells in people with ME/CFS, people with multiple sclerosis (MS), and healthy people. Researchers found that ME/CFS patients had higher levels of certain regulatory immune cells called Tregs, while MS patients had lower levels of gamma delta T cells. The findings suggest that ME/CFS and MS affect the immune system in different ways, rather than through the same mechanisms.

E2 ModerateCohortPEM unclearLongitudinal

Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients.

Hardcastle, Sharni Lee, Brenu, Ekua Weba, Johnston, Samantha et al.·Journal of translational medicine·2015

This study tracked immune system changes in 42 ME/CFS patients (divided into moderate and severe groups) and 18 healthy controls over 6 months. Researchers used blood tests to count different types of immune cells. They found that people with severe ME/CFS had noticeably different immune cell patterns than those with moderate ME/CFS or healthy controls, suggesting the immune system may work differently depending on how severe the illness is.