HERV activation segregates ME/CFS from fibromyalgia and defines a novel nosological entity for patients fulfilling both clinical criteria

Abstract

AbstractMyalgic 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.