Researchers have identified unique plasma immune signatures that appear earlier in the course of myalgic encephalomyelitis – also known as chronic fatigue syndrome – but which are not present in individuals with a longer duration of illness or healthy controls.
Analysis of data from two large, multicenter cohort studies in 298 cases and 348 controls showed that patients with shorter duration of illness were more than 100 times more likely to have a higher level of interferon-gamma (odds ratio, 104.777; 95% confidence interval, 6.975-1574.021; P = .001) and 50% more likely to have a higher level of interleukin (IL)-12p40 (OR, 1.501; 95% CI, 1.075-2.096; P = .017) than were those with a longer duration of illness.
Overall, researchers noted significant differences in more than half the 51 cytokines studied according to the duration of illness, finding that individuals with shorter illness duration (3 or fewer years; 52 patients) generally had higher cytokine levels than did those with longer duration (246 patients), Dr. Mady Hornig of Columbia University, New York, and coauthors reported online Feb. 27 in Science Advances.
Compared with healthy controls, patients with a shorter duration of illness had significantly elevated classical proinflammatory cytokines, such as IL-1a, IL-8, IL-12, IL-17A, and TNF-alpha, and anti-inflammatory cytokines such as IL-1 receptor antagonist, IL-4, and IL-13.
However, they also had reduced levels of CD40 ligand (CD40L) and platelet-derived growth factor BB (PDGFBB), compared with controls (Sci. Adv. 2015;1:e1400121 [doi:10.1126/sciadv.1400121]).
“For cytokines that differed between short- and long-duration groups, levels were correlated with duration of illness, and in the expected direction: inverse correlations with duration of illness for cytokines that were increased in the short-duration group, and positive correlations for the two cytokines with reduced levels in the short-duration group,” the investigators wrote.
But when long-duration subjects were compared with healthy controls, the opposite was true; those cytokines that were elevated in patients with short-duration illness, compared with controls, were lower than controls in patients with long-duration illness, with the exception of CD40L and PDGFBB.
When patients with short and long duration of illness were combined into one group, the analysis showed no significant differences in plasma immune signatures, compared with healthy controls.
The analysis also revealed unusual regulatory relationships among the cytokines in the short-duration illness group that were not evident in controls or the long-duration illness group.
“Whereas CD40L drove most of the inverse relationships with other immune molecules in long-duration ME/CFS and controls, CD40L was only related to five other cytokines in the short-duration ME/CFS group; furthermore, only one of these associations, PDGFBB, was negative,” the authors wrote.
The authors said this was the first study to show altered plasma immune signatures early in the course of myalgic encephalomyelitis that are not evident either in healthy controls or in patients who have had the illness for longer.
Previous efforts to identify immune biomarkers of myalgic encephalomyelitis have led to inconclusive findings, and laboratory assays are only used to rule out other conditions rather than to make a positive diagnosis of the disease.
The study was funded by the Chronic Fatigue Initiative at Hutchins Family Foundation and the National Institutes of Health. The authors declared no conflicts of interest.