Researchers at the Stanford University School of Medicine have linked chronic fatigue syndrome to variations in 17 immune-system signalling proteins, or cytokines, whose concentrations in the blood correlate with the disease\u2019s severity.
The findings provide evidence that inflammation is a powerful driver of this mysterious condition, whose underpinnings have eluded researchers for 35 years.
\u201cChronic fatigue syndrome can turn a life of productive activity into one of dependency and desolation,\u201d said Jose Montoya, MD, professor of infectious diseases, who is the study\u2019s lead author. Some spontaneous recoveries occur during the first year, he said, but rarely after the condition has persisted more than five years.
The study\u2019s senior author is Mark Davis, PhD, professor of immunology and microbiology and director of Stanford\u2019s Institute for Immunity, Transplantation and Infection.
\u201cThere\u2019s been a great deal of controversy and confusion surrounding myalgic encephalomyelitis (ME) CFS \u2014 even whether it is an actual disease,\u201d said Davis. \u201cOur findings show clearly that it\u2019s an inflammatory disease and provide a solid basis for a diagnostic blood test.\u201d
Many, but not all, ME\/CFS patients experience flulike symptoms common in inflammation-driven diseases, Montoya said. But because its symptoms are so diffuse \u2014sometimes manifesting as heart problems, sometimes as mental impairment nicknamed \u201cbrain fog,\u201d other times as indigestion, diarrhea, constipation, muscle pain, tender lymph nodes and so forth \u2014 it often goes undiagnosed, even among patients who\u2019ve visited a half-dozen or more different specialists in an effort to determine what\u2019s wrong with them.
The sporadic effectiveness of antiviral and anti-inflammatory drugs has spurred Montoya to undertake a systematic study to see if the inflammation that\u2019s been a will-o\u2019-the-wisp in those previous searches could be definitively pinned down.
To attack this problem, he called on Davis, who helped create the Human Immune Monitoring Center. Since its inception a decade ago, the centre has served as an engine for large-scale, data-intensive immunological analysis of human blood and tissue samples. Directed by study co-author Holden Maecker, PhD, a professor of microbiology and immunology, the centre is equipped to rapidly assess gene variations and activity levels, frequencies of numerous immune cell types, blood concentrations of scores of immune proteins, activation states of intercellular signalling models, and more on a massive scale.
This approach is akin to being able to look for and find larger patterns \u2014 analogous to whole words or sentences \u2014 in order to locate a desired paragraph in a lengthy manuscript, rather than just try to locate it by counting the number of times in which the letter A appears in every paragraph.
The scientists analysed blood samples from 192 of Montoya\u2019s patients, as well as from 392 healthy control subjects. The average age of patients and controls was about 50. Patients\u2019 average duration of symptoms was somewhat more than 10 years.
Importantly, the study design took into account patients\u2019 disease severity and duration. The scientists found that some cytokine levels were lower in patients with mild forms of ME\/CFS than in the control subjects, but elevated in ME\/CFS patients with relatively severe manifestations. Averaging the results for patients versus controls with respect to these measures would have obscured this phenomenon, which Montoya said he thinks may reflect different genetic predispositions, among patients, to progress to mild versus severe disease.
When comparing patients versus control subjects, the researchers found that only two of the 51 cytokines they measured were different. Tumour growth factor beta was higher and resistin was lower in ME\/CFS patients. However, the investigators found that the concentrations of 17 of the cytokines tracked disease severity. Thirteen of those 17 cytokines are pro-inflammatory.
TGF-beta is often thought of as an anti-inflammatory rather than a pro-inflammatory cytokine. But it\u2019s known to take on a pro-inflammatory character in some cases, including certain cancers. ME\/CFS patients have a higher than normal incidence of lymphoma, and Montoya speculated that TGF-beta\u2019s elevation in ME\/CFS patients could turn out to be a link.
One of the cytokines whose levels corresponded to disease severity, leptin, is secreted by fat tissue. Best known as a satiety reporter that tells the brain when somebody\u2019s stomach is full, leptin is also an active pro-inflammatory substance. Generally, leptin is more abundant in women\u2019s blood than in men\u2019s, which could throw light on why more women than men have ME\/CFS.
\n
Stanford Medicinehttp:\/\/tinyurl.com\/y7agngxn<\/link>\n","protected":false},"excerpt":{"rendered":"
Researchers at the Stanford University School of Medicine have linked chronic fatigue syndrome to variations in 17 immune-system signalling proteins, or cytokines, whose concentrations in the blood correlate with the disease\u2019s severity.The findings provide evidence that inflammation is a powerful driver of this mysterious condition, whose underpinnings have eluded researchers for 35 years.\u201cChronic fatigue syndrome […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[35],"tags":[],"_links":{"self":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/987"}],"collection":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/comments?post=987"}],"version-history":[{"count":0,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/987\/revisions"}],"wp:attachment":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/media?parent=987"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/categories?post=987"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/tags?post=987"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}