Eaton-Fitch et al. (2025)
- Authors: Natalie Eaton-Fitch, Etianne Martini Sasso, Sonya Marshall-Gradisnik.
- Institutes: National Centre for Neuroimmunology and Emerging Diseases, Griffith University; Consortium Health International for Myalgic Encephalomyelitis, Griffith University.
- Publisher: PLOS One
- Link: DOI
Summary
This research provides evidence that Gulf War Illness involves measurable changes in how the immune system functions at a genetic level, many of which overlap with observations in other chronic fatiguing illnesses like ME/CFS. By identifying 33 specific genes that are âswitched on or offâ differently in patients, the study moves closer to finding an objective biological signature for a condition that has long been difficult to diagnose. While the results are preliminary due to the small cohort, they suggest that chronic inflammation and metabolic stress are core features of the illness, potentially opening the door for future diagnostic tests and therapies aimed at regulating these immune pathways.
What was researched?
This study investigated changes in the gene expression (transcriptomics) of immune cells in Australian veterans diagnosed with Gulf War Illness (GWI). Researchers analyzed a specific panel of 785 genes related to immune exhaustion and inflammation to identify potential biological markers for the disease.
Why was it researched?
Gulf War Illness is a chronic condition affecting approximately one-third of Gulf War veterans, characterized by symptoms like chronic fatigue and brain fog. Despite its prevalence, the biological cause remains elusive, though it is strongly linked to toxic environmental exposures. This research aimed to fill a knowledge gap regarding the specific immune signaling pathways and genetic signatures that may drive the illness in Australian cohorts.
How was it researched?
The researchers conducted a laboratory analysis of peripheral blood mononuclear cells (PBMCs) from 20 Australian GWI veterans and 15 healthy controls. Participants were sex-matched (all male) and diagnosed using the CDC and Kansas criteria. The team used NanoString technology to quantify the expression of hundreds of immune-related genes and applied pathway analysis to determine how these genetic changes affect cellular functions like stress response and inflammation.
What has been found?
The study identified 33 genes that were expressed differently in GWI patients compared to healthy individuals, with 21 genes being more active (upregulated) and 12 being less active (downregulated). Upregulated genes, such as SIGLEC1 and MMP9, were associated with metabolic stress and cellular defense, while downregulated genes, including IL7 and various T cell receptors, suggested a weakened adaptive immune response. These findings point to chronic inflammation and specific disturbances in interferon and tumor necrosis factor (TNF) signaling pathways.
Discussion
The authors noted that while specific markers of âimmune exhaustionâ did not differ statistically from controls, the overall genetic patterns suggest a state of chronic immune activation and cellular stress. They emphasize that the identified changes in neutrophil signaling and lipid-related pathways provide a clearer map of the inflammation present in GWI. A primary limitation acknowledged is the small sample size, which requires larger-scale studies to confirm these markers.
Conclusion & Future Work
The investigation concludes that GWI is characterized by significant immune dysregulation, particularly involving pathways that control how the body responds to infections and stress. The researchers suggest that the identified genetic markers could eventually be used for diagnostic screening or as targets for new treatments. Future work will focus on validating these findings in a larger, more diverse group of patients to improve the accuracy of GWI detection.