Chronic fatigue syndrome is a debilitating disorder characterized by severe fatigue that lasts for more than 6 months. The condition is also accompanied by a range of symptoms, from muscle pain and headaches to cognitive dysfunction. The illness can sometimes be difficult to diagnose, and its cause is not yet known. However, new research finds the biological basis for two subgroups of chronic fatigue syndrome, which may in the future help clinicians to diagnose the disease and treat it more effectively.
Chronic fatigue syndrome (CFS), also sometimes referred to as myalgic encephalomyelitis (ME), affects more than 1 million people in the United States. The disease is usually most prevalent in women in their 40s and 50s, with CFS being four times more frequent in women than in men.
Symptoms include joint pain, painful lymph nodes, having trouble sleeping, and headaches, as well as difficulty concentrating and remembering things. Medical professionals do not yet know what causes the disease.
CFS is difficult to identify as there is no test for it, and because it shares some of its symptoms with other illnesses. However, new research investigates the biological basis for the illness and identifies two subgroups of CFS that go on to develop differently: the so-called classical CFS and an “atypical” variant.
The study was carried out by researchers at the Center for Infection and Immunity (CII) at Columbia University’s Mailman School of Public Health in New York, and it was led by Dr. Mady Hornig, director of translational research at CII and associate professor of epidemiology at the university. The results were published in the journal Translational Psychiatry.
Hornig and team performed immunoassays to measure 51 immune biomarkers in the cerebrospinal fluid of 32 people with classical CFS, and another 27 with atypical CFS.
The tests showed lower levels of immune molecules in those with atypical CFS than in those with the classical variant. The analyses revealed drastically lower levels of interleukin 7 (a protein that plays a key role in the adaptive immune response to infections), interleukin 17A, and chemokine ligand 9 (molecules with a key role in the adaptive immunity to neurological illnesses).
Additionally, these biological features were accompanied by different trajectories of disease history and comorbidities. Those with atypical CFS tended to have a history of viral encephalitis and tended to fall ill after traveling abroad or receiving a blood transfusion. Furthermore, people with atypical CFS went on to develop simultaneous conditions such as seizure disorders, several types of cancers, or demyelinating disorders – that is, multiple sclerosis-like diseases that damage myelin, the protective sheath around the nerve cells in our brains and spinal cords.
“We now have biological evidence that the triggers for ME/CFS may involve distinct pathways to disease, or, in some cases, predispose individuals to the later development of serious comorbidities. Importantly, our results suggest that these early biomarker profiles may be detectable soon after diagnosis of ME/CFS, laying a foundation for better understanding of and treatments for this complex and poorly understood illness.”
Dr. Mady Hornig
The senior author of the study and director of CII, Dr. Ian Lipkin, also explains the contribution of the findings:
“Multiple biological pathways are likely involved in the pathogenesis of ME/CFS, with a range of clinical subtypes relating to variability in the types of environmental triggers, genetic and epigenetic vulnerability, as well as comorbidity patterns,” he says. “Shedding light on these pathways may help us to identify the various agents that precipitate disease as well as to design more precise, targeted treatments.”
Overall, both atypical and classical CFS patients were revealed to have an abnormal immune system when compared with the general population.
However, only people with classical CFS displayed the previously discovered 3-year mark of CFS – namely, after 3 years of having an “overzealous” immune system, CFS patients show signs of immune “exhaustion,” with dramatic drops in their levels of immune molecules.
In this new study, only those with classical CFS had this drop in immune molecules after 3 years, whereas those with atypical CFS displayed steady or increased levels of cytokines and chemokines – proteins that control the development and activation of immune cells.
Study co-author Dr. Daniel L. Peterson, principal clinician at Sierra Internal Medicine in Incline Village, NV, comments on the significance of these findings:
“Early identification of patients who meet the usual clinical criteria when first diagnosed but then go on to develop atypical features would help clinicians like myself identify and treat these complex cases and even prevent fatal outcomes.”
Hornig speculates on the mechanism that might be responsible for the differences between the two subgroups. She suggests that atypical patients may go through a “smoldering inflammatory process,” in which their body’s immune system is trying to recover, but she notes that further research is needed in order to test this hypothesis.
She also suggests that genetic predispositions may cause the immune system to respond differently in atypical individuals.
Researchers at CII continue to investigate other subgroups of CFS patients, such as patients with allergies, cognitive impairment, and gastrointestinal problems.