PDB_1eku_EBI

Crystal structure of a biologically active single chain mutant of human interferon gamma

A new scientific paper from the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health has revealed “distinct plasma immune signatures” in the early stages of ME/CFS. The report – which appears in the AAAS journal, Science Advances, and has Prof Ian Lipkin and Prof Nancy Klimas among its co-authors – describes the measurement of 51 immune biomarkers in blood plasma samples collected from 2 large multicenter studies, representing 298 ME/CFS patients and 348 healthy controls.

The headline finding is that patients who had the disease for three years or less had a specific immune ‘signature’ that was not present in healthy controls or in patients who had been ill for more than three years. Patients with a shorter duration of illness had increased amounts of many different types of immune molecules called cytokines. In particular, there was a marked association with the cytokine interferon gamma that has been linked to the fatigue that follows many viral infections, including Epstein-Barr virus which causes infectious mononucleosis (glandular fever). Age affected the results, but the immune differences could not be explained by age differences between the short-duration illness and long-duration illness groups.

Mady Hornig, M.D., lead author and director of translational research at the Center for Infection and Immunity at Columbia University's Mailman School of Public Health

Mady Hornig, M.D., lead author and director of translational research at Columbia University’s Mailman School of Public Health

As lead author Prof Mady Hornig, director of translational research at the Center for Infection, points out, ME/CFS patients seem to be flush with cytokines until around the 3-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop. The results support the idea that ME/CFS may reflect an infectious ‘hit-and-run’ event. Patients often report getting sick, sometimes from something as common as infectious mononucleosis, and never fully recover. These infections throw a wrench in the immune system’s ability to quiet itself after the acute infection; the immune response becomes like a car stuck in high gear.

“We now have evidence confirming what millions of people with this disease already know, that ME/CFS isn’t psychological…”, says Prof Hornig. And Prof Ian Lipkin comments, “This study delivers what has eluded us for so long: unequivocal evidence of immunological dysfunction in ME/CFS and diagnostic biomarkers for disease…The question we are trying to address in a parallel microbiome project is what triggers this dysfunction.”

The scientific results of Columbia University’s study have had lots of media coverage across the world. One story in the Daily Mail describes the findings, and gives the experience of Harpist Claire Jones who was floored by the illness. Also, the story points out that Dr Hornig’s team is now looking for signs of the infection that triggered the immune response, and it quotes Dr Neil Abbot of ME Research UK as saying: “A biological signature or thumbprint for ME is the holy grail – it’s what we all want to see. If the immune changes reported in the study can help, it would be a great step forward.”

Scientific Abstract

Distinct plasma immune signatures in ME/CFS are present early in the course of illness (Full text)

Mady Hornig, et al. Science Advances 2015 Feb 27. Epub ahead of print.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing of sample collection during the course of the illness. Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables. Controls were frequency-matched on key variables known to affect immune status, including season of sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the course of ME/CFS (n = 52) relative to healthy controls (n = 348) that are not present in subjects with longer duration of illness (n = 246). Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical implications for discovery of interventional strategies and early diagnosis of ME/CFS.

Further reading

Press release from Columbia University

Original report in Science Advances