Evidence browser

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.

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.

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.

E2 ModerateCohortPEM unclearCase-Control

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.

E2 ModerateCohortPEM unclearCase-Control

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.

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.

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.

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.

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.

Frequent IgG subclass and mannose binding lectin deficiency in patients with chronic fatigue syndrome.

Guenther, Sabrina, Loebel, Madlen, Mooslechner, Agnes A et al.·Human immunology·2015

This study looked at immune system proteins called antibodies and a molecule called mannose binding lectin (MBL) in 300 people with ME/CFS. The researchers found that about 25% of patients had lower-than-normal levels of certain antibodies, while another 25% had higher-than-normal levels. Additionally, 15% had low MBL levels, compared to only 6% in healthy people. These immune defects were connected to frequent respiratory infections in ME/CFS patients.

Cytokines in the cerebrospinal fluids of patients with chronic fatigue syndrome/myalgic encephalomyelitis.

Peterson, D, Brenu, E W, Gottschalk, G et al.·Mediators of inflammation·2015

Researchers tested cerebrospinal fluid (the fluid around the brain and spinal cord) from ME/CFS patients and healthy controls to see if immune chemicals called cytokines were different. Out of 27 different immune chemicals tested, they found that only one—called IL-10—was lower in ME/CFS patients. This suggests that immune system problems in the brain and nervous system may play a role in ME/CFS symptoms.

Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis/chronic fatigue syndrome: inverse associations with lowered CD19+ expression and CD4+/CD8+ ratio, but no associations with (auto)immune, leaky gut, oxidative and nitrosative stress biomarkers.

Maes, Michael, Bosmans, Eugene, Kubera, Marta·Neuro endocrinology letters·2015

This study examined immune cells called CD8+ T lymphocytes in ME/CFS patients and found they show higher levels of activation markers (CD38 and HLA-DR) compared to healthy people and those with regular fatigue. The researchers measured 139 ME/CFS patients, 65 with chronic fatigue, and 40 healthy controls, finding distinct immune patterns in ME/CFS that don't appear to be directly linked to inflammation, gut problems, or oxidative stress.

E2 ModerateCohortPEM not requiredLongitudinal

Increased Risk of Chronic Fatigue Syndrome Following Atopy: A Population-Based Study.

Yang, Tse-Yen, Kuo, Haung-Tsung, Chen, Hsuan-Ju et al.·Medicine·2015

This study tracked over 200,000 people for 4-6 years to see if allergies and atopic conditions (like asthma, eczema, and hay fever) increase the risk of developing ME/CFS. People with atopy were 1.5 times more likely to develop ME/CFS than those without atopy, and the risk was even higher for people with multiple atopic conditions. This suggests a possible link between the body's allergic responses and the development of ME/CFS.

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.

Role of polymorphisms of inducible nitric oxide synthase and endothelial nitric oxide synthase in idiopathic environmental intolerances.

De Luca, Chiara, Gugliandolo, Agnese, Calabrò, Carlo et al.·Mediators of inflammation·2015

This study looked at genetic variations in genes that control nitric oxide (a chemical messenger in the body) in people with ME/CFS, fibromyalgia, and chemical sensitivities. Researchers found that certain genetic patterns were more common in these patient groups and were associated with higher levels of oxidative stress markers, suggesting these genetic differences might play a role in these overlapping conditions.

E2 ModerateCohortPEM requiredCross-Sectional

A new case definition of Neuro-Inflammatory and Oxidative Fatigue (NIOF), a neuroprogressive disorder, formerly known as chronic fatigue syndrome or Myalgic Encephalomyelitis: results of multivariate pattern recognition methods and external validation by neuro-immune biomarkers.

Maes, Michael·Neuro endocrinology letters·2015

This study looked at whether ME/CFS could be better understood by examining specific blood markers related to inflammation, oxidative stress, and immune activation. Researchers found two distinct groups of people with chronic fatigue—one group had significantly higher levels of problematic immune markers and inflammatory signs. The study proposes a new way to identify ME/CFS based on fatigue plus at least four of these symptoms: muscle tension, memory problems, sleep issues, digestive problems, headaches, or flu-like feelings.

Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis.

Khaiboullina, Svetlana F, DeMeirleir, Kenny L, Rawat, Shanti et al.·Cytokine·2015

This study looked at chemical messengers in the blood called cytokines to understand Gulf War illness (GWI) and ME/CFS better. Researchers found that certain cytokines could identify ME/CFS patients very well, but were less reliable for GWI patients. The findings suggest that while GWI and ME/CFS share many similar symptoms, they may have different underlying immune system problems.

Serum Immune Proteins in Moderate and Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients.

Hardcastle, Sharni Lee, Brenu, Ekua Weba, Johnston, Samantha et al.·International journal of medical sciences·2015

This study looked at immune system proteins in the blood of people with ME/CFS, comparing those with moderate and severe illness to healthy people. Researchers found that different immune markers were present at different levels depending on how severe someone's illness was. This suggests that ME/CFS may actually involve different immune patterns in different people, which could help researchers better understand why treatments don't work the same way for everyone.

Plasma cytokine expression in adolescent chronic fatigue syndrome.

Wyller, Vegard Bruun, Sørensen, Øystein, Sulheim, Dag et al.·Brain, behavior, and immunity·2015

This study measured inflammation markers called cytokines in the blood of 120 adolescents with ME/CFS and compared them to 68 healthy young people. Despite CFS patients reporting significantly more fatigue and symptoms suggesting inflammation, the researchers found no differences in cytokine levels or inflammation patterns between the two groups. This suggests that the fatigue and symptoms in adolescent ME/CFS may not be caused by the type of low-grade inflammation in the blood that researchers had previously suspected.

Sympathetic activation is associated with increased IL-6, but not CRP in the absence of obesity: lessons from postural tachycardia syndrome and obesity.

Okamoto, Luis E, Raj, Satish R, Gamboa, Alfredo et al.·American journal of physiology. Heart and circulatory physiology·2015

This study looked at how an overactive nervous system relates to inflammation in the body. Researchers compared people with POTS (a condition causing increased heart rate when standing) to healthy controls, both lean and obese. They found that an overactive nervous system was linked to higher levels of IL-6, a marker of inflammation, even in people without obesity—but only obesity combined with nervous system overactivity produced high CRP, another inflammation marker.