New Insights into Immune System Irregularities in Chronic Fatigue Syndrome Patients

A comprehensive study conducted by researchers at Columbia University's Mailman School of Public Health has unveiled important molecular-level details about the immune system's behavior in individuals suffering from chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME/CFS). The research highlights an overactive innate immune response in these patients, particularly to microbes such as bacteria, viruses, and fungi. While robust immune responses are essential for fighting infections, unchecked responses can lead to tissue damage and persistent inflammation.

The study involved analyzing blood samples from 56 ME/CFS patients and 52 healthy controls across New York and California. Using advanced molecular techniques, scientists mapped both the metabolome (metabolites involved in cellular energy and metabolism) and the proteome (the entire set of proteins). They also examined immune responses to simulated infections, including post-exercise assessments.

Findings indicate that ME/CFS patients exhibit disruptions in interconnected biological processes, often seen in chronic inflammatory states. These include impaired cellular energy production, lipid metabolism abnormalities, and disruptions in the extracellular matrix, which supports tissue structure and immune signaling. The study also revealed compromised gut barrier integrity, leading to increased bacterial translocation and systemic inflammation.

Moreover, overactivation of the innate immune system’s complement pathway and disturbances in antioxidant processes driven by copper dependency were observed. These disturbances contribute to ongoing tissue damage and fatigue. Immune cells from patients, specifically Peripheral Blood Mononuclear Cells, responded with increased cytokine production, such as IL-6, when stimulated with bacterial and viral mimetics, especially in women over 45 with lower estrogen levels.

The research suggests that these molecular and immune abnormalities might underpin the chronic symptoms seen in ME/CFS, including persistent fatigue, cognitive issues, and post-exertional malaise. Importantly, the study proposes several potential targets for clinical trials, including medications like metformin, rapamycin, and immunomodulatory cytokines, as well as gut microbiome interventions. These findings pave the way for precision medicine approaches to treat different subtypes of ME/CFS based on metabolic and immune profiles.

This research enhances our understanding of ME/CFS as a physical, rather than purely psychological, disorder and emphasizes the role of immune dysregulation in its pathology. It also highlights the importance of exploring molecular biomarkers for improved diagnosis and targeted therapy development.

Source: https://medicalxpress.com/news/2025-09-reveals-overactive-immune-patients-chronic.html