Preprint HERV activation segregates ME/CFS from FM and defines a novel nosological entity for patients fulfilling both clinical criteria, 2023, Gimenez-Orenga

Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia (FM) are chronic diseases with poorly understood pathophysiology and diagnosis based on clinical assessment of unspecific symptoms. The recent post-COVID-19 condition, which shares similarities with ME/CFS and FM, has raised concerns about viral-induced transcriptome changes in post-viral syndromes. Viral infections, and other types of stress, are known to unleash human endogenous retroviruses (HERV) repression that if maintained could lead to symptom chronicity.

This study evaluated this possibility for ME/CFS and FM on a selected cohort of female patients complying with diagnosis criteria for ME/CFS, FM, or both, and matched healthy controls (n=43). The results show specific HERV fingerprints for each disease, confirming biological differences between ME/CFS and FM. Unexpectedly, HERV profiles segregated patients that met both ME/CFS and FM clinical criteria from patients complying only with ME or FM criteria, while clearly differentiating patients from healthy subjects, supporting that the highly prevalent comorbidity condition must constitute a different nosological entity. Moreover, HERV profiles exposed significant quantitative differences within the ME/CFS group that correlated with differences in immune gene expression and patient symptomatology, supporting ME/CFS patient subtyping and confirming immunological disturbances in this disease.

Pending issues include validation of HERV profiles as disease biomarkers of post-viral syndromes and understanding the role of HERV during infection and beyond.

https://www.biorxiv.org/content/10.1101/2023.10.05.561025v1

 

Similar to a previous study HERV-W and HERV-K again don’t seem to play a major role in ME/CFS (here they even seem to be downregulated in ME/CFS, FM and other comobidities). On the other hand a larger role was suggested in Covid and Long Covid https://autoimmunhighlights.biomedcentral.com/articles/10.1186/s13317-019-0122-8, https://www.frontiersin.org/articles/10.3389/fimmu.2022.1020064/full (allegedly the W-ENV positivity rate in LC is even above 30% https://www.businesswire.com/news/h...lf-Year-Results-and-Provides-Corporate-Update).

As such it seems relevant to me to know whether some of these ME/CFS case are due to Covid or at least consider the disease duration and whether participants in the study recently had a Covid infection (or possibly a different stressor?) if the testing can heavily depend on a viral infection.

How much of all this is just pure noise is not possible for me to tell. But I'm sure the smart people on this forum can provide some answers.

 

p. 2 of the pdf--https://www.biorxiv.org/content/10.1101/2023.10.05.561025v1.full.pdf

"Previous studies found overexpression of some HERV families in immune cells of ME/CFS
(33) and FM (34) at the transcript level. However, the study and comprehension of HERV in
ME/CFS and FM are still at infancy. In this study, we hypothesized that genome-wide HERV
profiling of ME/CFS and FM could reveal distinct underlying pathomechanisms that justify
their separate classification, and/or common fingerprints explaining their high comorbid
prevalence."