HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab.
Martín-Martínez, Eva, Gil-Perotin, Sara, Giménez-Orenga, Karen et al. · International journal of molecular sciences · 2025 · DOI
Quick Summary
This study describes one patient who had ME/CFS and was later diagnosed with multiple sclerosis (MS). Doctors discovered that his blood had unusual patterns of human endogenous retroviruses (HERVs)—ancient viral-like sequences in our DNA that can sometimes affect immune function. Importantly, this patient improved significantly after receiving rituximab, a treatment that modifies the immune system, even though standard treatments had not worked for him.
Why It Matters
This case suggests that HERV dysregulation may play a role in ME/CFS and related autoimmune conditions, and that examining the full HERV landscape rather than single proteins might reveal new treatment targets. The dramatic response to rituximab in this patient adds to evidence that B-cell directed therapy merits further investigation in ME/CFS, potentially opening new therapeutic avenues beyond current standard approaches.
Observed Findings
Distinct HERV transcriptome profile detected via genome-wide microarray analysis in patient blood
Absence of elevated HERV-W ENV protein expression despite widespread HERV dysregulation
Clinical improvement following rituximab treatment after failure of prior therapies
Secondary MS diagnosis emerging 8 years after initial ME/CFS diagnosis
Longitudinal follow-up revealing disease progression over decade-long observation period
Inferred Conclusions
HERV dysregulation may contribute to immune pathology in ME/CFS and comorbid MS
Multiple HERV elements beyond HERV-W may encode therapeutically relevant targets in these conditions
Rituximab's efficacy in this patient suggests B-cell dysfunction may be mechanistically important
Genome-wide HERV analysis may be more informative than single-protein biomarkers for understanding disease biology
Remaining Questions
Do other ME/CFS patients show similar HERV dysregulation patterns, or was this patient's profile unique?
Would post-rituximab HERV reassessment show normalization of the dysregulated profile, suggesting a mechanistic link?
What This Study Does Not Prove
This is a single case report and cannot establish causation between HERV dysregulation and ME/CFS or MS symptoms. The study does not prove that the observed HERV profile was responsible for rituximab's effectiveness, nor does it demonstrate that other ME/CFS patients will have similar HERV profiles or treatment responses. The absence of elevated HERV-W ENV suggests other HERV elements may be relevant, but this remains speculative without larger cohort validation.