A new study led by Stanford chronic fatigue syndrome expert Jose Montoya, MD, and published in the Proceedings of the National Academy of Sciences has linked chronic fatigue syndrome to variations in 17 immune-system signaling proteins, or cytokines, whose concentrations in the blood correlate with the disease’s severity.
The findings strongly suggest that inflammation is a powerful driver of this mysterious condition, whose underpinnings have eluded researchers for 35 years.
In a news release about the study, I wrote:
More than 1 million people in the United States suffer from chronic fatigue syndrome… It is a disease with no known cure or even reliably effective treatments. Three of every four … patients are women, for reasons that are not understood. It characteristically arises in two major waves: among adolescents between the ages of 15 and 20, and in adults between 30 and 35. The condition typically persists for decades.
Chronic fatigue syndrome’s symptoms are so diffuse — sometimes manifesting as heart problems, sometimes as mental impairment nicknamed “brain fog,” other times as indigestion, diarrhea, constipation, muscle pain, tender lymph nodes and so forth — that it often goes undiagnosed, even among patients who’ve visited a half-dozen or more different specialists in an effort to determine what’s wrong with them.
In fact, there’s been a long history of questioning whether it is even an actual disease. But Montoya and immunologist Mark Davis, PhD, who played a pivotal role in creating Stanford’s Human Immune Monitoring Center — a high-tech facility that serves as an engine for large-scale, data-intensive immunological analysis of human blood and tissue samples — thought otherwise. So they and a number of other scientists brought blood samples from 192 of Montoya’s patients and from 392 healthy control subjects into the center for an intensive analysis of individual subjects’ gene variations and activity levels, frequencies of their diverse immune cell types, blood concentrations of scores of their circulating immune proteins, activation states of signaling molecules inside their cells, and more.
The investigators identified a “signature” composed of 17 cytokines whose concentrations in blood tracked disease severity.
Importantly, the study design had separated patients into separate categories depending on disease severity. Montoya and his colleagues found that some cytokine levels were lower in patients with mild forms of the syndrome than in the control subjects, but elevated in patients with relatively severe manifestations. Averaging the results for patients versus controls with respect to these measures would have completely obscured this phenomenon.
“I have seen the horrors of this disease, multiplied by hundreds of patients,” Montoya told me in a conversation about the study. “It’s been observed and talked about for 35 years now, sometimes with the onus of being described as a psychological condition. But chronic fatigue syndrome is by no means a figment of the imagination. This is real.”