Evidence browser

A case-control study on the association between rheumatoid arthritis and bladder pain syndrome/interstitial cystitis.

Keller, Joseph J, Liu, Shih-Ping, Lin, Herng-Ching·Neurourology and urodynamics·2013

This study looked at whether people with rheumatoid arthritis (an autoimmune disease that causes joint inflammation) are more likely to have bladder pain syndrome/interstitial cystitis (BPS/IC, a chronic bladder condition). Researchers compared nearly 9,300 people with BPS/IC to over 46,000 people without it, using insurance records from Taiwan. They found that people with BPS/IC were about 1.7 times more likely to have a history of rheumatoid arthritis than those without BPS/IC, even after accounting for other health conditions.

NeuroinflammationImmune System

In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation.

Maes, Michael, Ringel, Karl, Kubera, Marta et al.·Journal of affective disorders·2013

This study found that people with ME/CFS often develop antibodies (immune proteins) against serotonin, a chemical messenger in the brain. These antibodies were linked to higher levels of inflammation, signs of bacteria leaking from the gut, and worse symptoms including pain, fatigue, brain fog, and mood changes. The findings suggest ME/CFS involves immune system problems that may contribute to the condition's core symptoms.

Humoral and cellular immune responses after influenza vaccination in patients with chronic fatigue syndrome.

Prinsen, Hetty, de Vries, I Jolanda M, Torensma, Ruurd et al.·BMC immunology·2012

This study tested how well people with ME/CFS respond to the flu vaccine compared to healthy people. Researchers measured both antibody production (humoral immunity) and T cell activity (cellular immunity) before and after vaccination. The results showed that people with ME/CFS had immune responses to the flu vaccine that were similar to healthy controls, suggesting their immune systems can respond normally to this vaccine.

Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome.

Maes, Michael, Twisk, Frank N M, Kubera, Marta et al.·Journal of affective disorders·2012

This study found that people with ME/CFS have higher levels of immune antibodies (IgA) that react to bacteria normally living in their gut. These elevated antibodies were connected to increased inflammation and immune system activation in the blood. The more of these antibodies patients had, the worse their symptoms—including fatigue, brain fog, and digestive problems—tended to be.

E2 ModerateCohortPEM requiredCross-Sectional

Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data.

Maes, Michael, Twisk, Frank N M, Johnson, Cort·Psychiatry research·2012

This study looked at whether ME, CFS, and chronic fatigue are truly different conditions or if they overlap too much to distinguish. Researchers tested 144 patients and found that post-exertional malaise (PEM)—where symptoms worsen after activity—is a key feature that separates ME from CFS. They also found that ME and CFS patients had higher levels of certain inflammatory markers in their blood compared to people with simple chronic fatigue.

BiomarkersImmune SystemPost-Exertional Malaise

E2 ModerateCohortPEM not requiredObservational

Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers.

Watt, Tessa, Oberfoell, Stephanie, Balise, Raymond et al.·Journal of medical virology·2012

This study looked at whether a antiviral medication called valganciclovir could help ME/CFS patients who had high levels of antibodies to two common viruses: HHV-6 and EBV. Sixty-one patients took the medication for varying lengths of time, and about half reported at least 30% improvement in their physical energy and thinking abilities. Interestingly, the improvement didn't depend on how high their antibody levels were at the start—patients improved simply from taking the medication, and those who took it longer did better.

Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults.

Chang, Cindy M, Warren, Joan L, Engels, Eric A·Cancer·2012

Researchers investigated whether people with ME/CFS have a higher risk of developing cancer. Using medical records from over 1.2 million elderly Americans, they found that people with ME/CFS had a slightly increased risk of non-Hodgkin lymphoma (a blood cancer), particularly certain subtypes. The study does not prove that ME/CFS causes cancer, but suggests that shared immune system problems or infections might explain the connection.

Increased autoimmune activity against 5-HT: a key component of depression that is associated with inflammation and activation of cell-mediated immunity, and with severity and staging of depression.

Maes, Michael, Ringel, Karl, Kubera, Marta et al.·Journal of affective disorders·2012

This study found that people with depression have more antibodies attacking serotonin (a brain chemical) compared to healthy people, especially those with severe depression. These antibodies were linked to higher inflammation, immune activation, fatigue, and cognitive problems. The more depressive episodes someone had experienced, the more likely they were to have these antibodies, suggesting that repeated depression may change the immune system over time.

No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome.

Burbelo, Peter D, Bayat, Ahmad, Wagner, Jason et al.·American journal of translational research·2012

This study tested whether a virus called HHV-6 might be causing chronic fatigue syndrome (ME/CFS). Researchers compared antibodies (immune system markers) against HHV-6 in people with ME/CFS and healthy controls. They found that both groups had similar levels of HHV-6 antibodies, suggesting this virus is unlikely to be a major cause of ME/CFS.

E2 ModerateBehavioralPEM not requiredCross-Sectional

Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome.

Lattie, Emily G, Antoni, Michael H, Fletcher, Mary Ann et al.·Brain, behavior, and immunity·2012

This study looked at whether people with ME/CFS who are better at managing stress have lower fatigue levels. Researchers measured stress management skills, emotional distress, fatigue, and inflammation markers in the blood and saliva of 117 people with ME/CFS. They found that people with better stress management skills reported less fatigue and emotional distress, and this benefit was especially strong in people who had higher levels of a specific inflammatory marker called IL-6.

E2 ModerateCohortPEM not requiredCross-Sectional

Antinuclear antibody detection by automated multiplex immunoassay in untreated patients at the time of diagnosis.

Op De Beéck, Katrijn, Vermeersch, Pieter, Verschueren, Patrick et al.·Autoimmunity reviews·2012

This study compared two different blood tests for detecting autoantibodies (proteins the immune system makes that attack the body's own cells) in patients with various autoimmune diseases and in people with ME/CFS. The researchers found that one newer automated test missed some antibodies that an older, more traditional test detected, and that having multiple antibodies together was much more common in autoimmune disease patients than in ME/CFS patients.

Fibromyalgia and chronic fatigue syndrome in children.

Itoh, Yasuhiko, Shigemori, Tomoko, Igarashi, Tohru et al.·Pediatrics international : official journal of the Japan Pediatric Society·2012

This study looked at two conditions that cause long-term pain and exhaustion in children: fibromyalgia and chronic fatigue syndrome. Researchers tested blood samples from children with each condition to see if they had similar immune system patterns. They found that while these conditions share some symptoms, they appear to have different immune system signatures, suggesting they may be separate diseases—though some children can have both.

Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin.

Maes, Michael, Twisk, Frank N M, Kubera, Marta et al.·Journal of affective disorders·2012

This study examined whether people with ME/CFS have higher levels of inflammatory markers—substances in the blood that signal inflammation—compared to healthy people and those with regular fatigue. Researchers found that ME/CFS patients had significantly elevated levels of five different inflammatory markers, and these markers were linked to common ME/CFS symptoms like fatigue, brain fog, and flu-like feelings. The findings suggest that low-grade inflammation in the body may be contributing to ME/CFS symptoms.

Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression.

Maes, Michael, Twisk, Frank N M, Ringel, Karl·Psychotherapy and psychosomatics·2012

This study found that people with ME/CFS have higher levels of inflammatory markers (immune chemicals) in their blood compared to people with depression, even though both conditions can cause fatigue and other similar symptoms. The researchers measured specific immune proteins and found that while both ME/CFS and depression involve some immune system changes, ME/CFS shows a distinctly different immune profile that helps distinguish it from depression.

E2 ModerateCohortPEM unclearLongitudinal

Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis.

Brenu, Ekua W, van Driel, Mieke L, Staines, Donald R et al.·Journal of translational medicine·2012

This study tracked immune system changes in 65 people with ME/CFS over one year, comparing them to 21 healthy controls. Researchers found that people with ME/CFS had consistently lower natural killer (NK) cell activity—immune cells that help fight infections—throughout the year. They also found changes in inflammatory molecules called cytokines that fluctuated at different time points.

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.

Immunophenotyping in post-giardiasis functional gastrointestinal disease and chronic fatigue syndrome.

Hanevik, Kurt, Kristoffersen, Einar K, Sørnes, Steinar et al.·BMC infectious diseases·2012

This study looked at immune system changes in people who developed chronic fatigue and gut problems after a Giardia infection. Researchers found that people with post-infectious chronic fatigue had lower levels of natural killer (NK) cells, which are important for fighting infections. The more severe someone's fatigue and stomach symptoms were, the lower their NK cells tended to be.

E2 ModerateCohortPEM not requiredObservational

Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue.

Broderick, Gordon, Katz, Ben Z, Fernandes, Henrique et al.·Journal of translational medicine·2012

This study followed 301 teenagers who had infectious mononucleosis caused by the Epstein-Barr virus (EBV) for two years. Some developed ME/CFS after their infection while others recovered completely. Researchers measured multiple immune molecules called cytokines in the blood to see if they could identify a pattern that distinguishes people with post-infectious ME/CFS from those who fully recovered.

Immune SystemPost-Exertional Malaise

Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Chapenko, Svetlana, Krumina, Angelika, Logina, Inara et al.·Advances in virology·2012

This study tested 108 ME/CFS patients and 90 healthy people for three viruses: HHV-6, HHV-7, and parvovirus B19. The researchers found that about 65% of ME/CFS patients had active viral infections compared to only 13% of healthy people. Patients with active viral infections showed higher levels of inflammatory markers and experienced more severe symptoms, especially when infected with multiple viruses at once.