An overly-enthusiastic immune system may be the elusive spark that ignites chronic fatigue syndrome (CFS).
Researchers at King's College London have now found the strongest evidence to date that when a particularly sensitive immune system is confronted, it can cause long-lasting fatigue that persists even after the infection is taken care of.
"For the first time, we have shown that people who are prone to develop a CFS-like illness have an overactive immune system, both before and during a challenge to the immune system," says Alice Russell, a psychiatrist who researches CFS at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN).
"Our findings suggest that people who have an exaggerated immune response to a trigger may be more at risk of developing CFS."
CFS, sometimes called myalgic encephalomyelitis (ME), is a mysterious illness that seems to defy explanation in spite of its debilitating reality. Primarily marked by unrelenting fatigue, this chronic condition can sometimes become so severe that patients can do little other than sleep, let alone get out of bed.
Yet even though it is thought to affect up to 17 million people worldwide, CFS remains relatively under-studied and tragically misunderstood. Today, we still cannot even diagnose it properly, let alone treat or cure it, and despite robust evidence, some remain convinced that it's entirely psychological.
Thankfully, in the last few years, things have started to turn around, and as research has begun to blossom, the immune system has emerged as a key culprit of CFS.
But while multiple studies have found incriminating evidence, the exact role that the immune system plays in CFS remains elusive. The newest findings come from the most rigorous biological investigation on this subject to date.
Since it's often unclear when CFS actually develops, the researchers turned their attention to a unique model that mimics its main symptom.
Recruiting 55 patients with chronic Hepatitis C (HCV), participants were treated with a drug, called Interferon alpha. This is a common treatment for HCV that can cause the same sort of response from the immune system as a powerful infection – basically, sending it into overdrive.
It's also known to cause acute fatigue, similar to CFS, and for some, this side-effect can last for many months after the treatment is completed.
Following the participants before, during and after treatment, the researchers identified 18 individuals who did not recover normally and instead developed lasting fatigue.
Before treatment, these patients had the same levels of fatigue as everybody else, but once treatment started, their fatigue was found to be more severe, persisting for months after.
An overactive immune system is likely to blame. In all 18 of these patients, the researchers found a much bigger immune response both before and during the treatment.
The findings suggest that some immune systems are more 'primed' to give exaggerated responses to infections, and this, in turn, can cause lasting fatigue.
But strangely enough, six months after treatment, this inflated immune response had all but disappeared - even though some patients were still suffering from persistent fatigue.
When they turned their attention to the fatigued patients, the researchers noticed something oddly similar: there was no obvious difference in the immune systems of 54 CFS patients compared to 57 healthy individuals.
It seems that by the time CFS-like illnesses develop, there are no longer any detectable differences that remain in the immune system.
This could be one of the reasons why CFS is so hard to catch and diagnose in its early stages. Because by the time we notice something is wrong, many of the clues have been wiped clean.
"In conclusion, findings from this study support the hypothesis that abnormal immune mechanisms are important in CFS, but only early in the course of the illness, around the time of the trigger, rather than when the syndrome is established," the authors conclude.
"Moreover, our study confirms the importance of the acute fatigue response to the trigger, rather than of the recovery period preceding the illness."
The findings are only based on a model of CFS, so more direct research will be needed, but the authors hope that their results will be a launching pad for better diagnosis in the future.
"A better understanding of the biology underlying the development of CFS is needed to help patients suffering with this debilitating condition," says co-author Carmine Pariante, an expert in biological psychiatry at King's College.
"Although screening tests are a long way off, our results are the first step in identifying those at risk and catching the illness in its crucial early stages."
This study has been published in Psychoneuroendocrinology.