Germain et al. (2025)
- Authors: Arnaud Germain, Jillian R. Jaycox, Christopher J. Emig, Aaron M. Ring, Maureen R. Hanson
- Institutes: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA, Division of Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, WA, USA, Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA, Augmenta Bioworks, Inc., Menlo Park, CA, USA
- Publisher: International Journal of Molecular Sciences
- Link: DOI
Summary
This research provides a significant challenge to the popular theory that autoantibodies against G-protein-coupled receptors (GPCRs) are a universal driver of ME/CFS. By using one of the most comprehensive screening methods to date, the study failed to find consistent autoantibody markers, suggesting that the search for a single diagnostic blood test remains elusive. However, the findings reinforce the importance of investigating viral reactivation and sex-based differences in immune responses.
What was researched?
The study performed a large-scale screening of over 7,500 antibody-antigen interactions to identify potential autoimmune markers in patients with ME/CFS.
Why was it researched?
It aimed to validate previous clinical reports suggesting that autoantibodies against receptors involved in autonomic and cardiovascular function are central to ME/CFS pathology.
How was it researched?
Researchers analyzed samples from 172 participants using two advanced platforms: a 1,134 autoantibody Luminex panel and Rapid Extracellular Antigen Profiling (REAP) covering over 6,000 human proteins and 225 viral antigens.
What has been found?
No significant differences in autoantibody levels were found between ME/CFS patients and healthy controls, including for previously implicated GPCRs. The data did reveal elevated levels of antibodies against certain herpesviruses in the patient group.
Discussion
The discrepancy with earlier studies might be due to the high-throughput nature of the tools used or the clinical heterogeneity within the patient cohort. Technical factors, such as whether antigens are presented as individual fragments or complete proteins, may also influence results.
Conclusion & Future Work
The results indicate that GPCR autoantibodies are likely not universal biomarkers for ME/CFS. Future research should focus on larger, stratified cohorts and the potential role of viral triggers in disease maintenance.