Tag: systemic lupus vs ME/CFS

Persistent symptom burden in long-standing systemic lupus erythematosus: a subgroup-focused hypothesis for an SLE-ME/CFS research phenotype

Abstract:

Background: Despite improved control of inflammatory disease activity in systemic lupus erythematosus (SLE), many patients experience persistent fatigue, impaired physical function, cognitive symptoms, sleep disturbance, and reduced exercise tolerance, including during remission. These symptoms are multifactorial and may not be adequately explained by conventional measures of inflammatory activity. Clinical and biological parallels with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest that interacting immune, metabolic, vascular, and autonomic mechanisms may contribute to persistent symptom burden in a subgroup of patients with long-standing SLE.

Objective: To develop a subgroup-focused, non-linear, and testable framework for persistent symptoms in SLE by integrating established SLE evidence with carefully distinguished mechanistic insights from ME/CFS research.

Methods: This Commentary is based on a targeted, non-systematic literature synthesis of publications identified in PubMed and Web of Science. Evidence was categorized as direct SLE evidence, evidence from ME/CFS, or cross-condition mechanistic inference. Priority was given to human studies, systematic reviews, meta-analyses, and translational research addressing persistent symptoms, autonomic and endothelial dysfunction, mitochondrial and redox alterations, and neurocognitive manifestations.

Results: We propose a hypothesized SLE-ME/CFS research phenotype characterized by persistent, functionally limiting symptoms despite low inflammatory disease activity or remission. The phenotype includes fatigue lasting at least six months together with post-exertional symptom exacerbation, unrefreshing sleep, cognitive symptoms, and/or orthostatic intolerance, following structured exclusion or assessment of alternative explanations and comorbidities. Direct SLE evidence supports the relevance of residual immune activation, oxidative stress, mitochondrial alterations, endothelial dysfunction, and dysautonomia. Findings from ME/CFS further suggest potentially convergent mechanisms involving impaired cellular energetics, autonomic dysfunction, altered cerebral perfusion, and neuroimmune dysregulation. However, these cross-condition inferences require direct validation in SLE.

Conclusions: Persistent symptom burden in long-standing SLE may reflect a biologically distinct subgroup in which immune, autonomic, vascular, metabolic, and neurocognitive mechanisms interact dynamically. The proposed framework does not define a new diagnostic entity or fixed disease trajectory but provides a hypothesis-generating basis for prospective longitudinal studies. Multidimensional phenotyping may improve patient stratification, biomarker discovery, and supportive care for patients whose symptoms remain disproportionate to conventional measures of disease activity.

Source: Habermann-Horstmeier L. Persistent symptom burden in long-standing systemic lupus erythematosus: a subgroup-focused hypothesis for an SLE-ME/CFS research phenotype. J Transl Med. 2026 Sep 25;24(1):1215. doi: 10.1186/s12967-026-08867-8. PMID: 42806386. https://link.springer.com/article/10.1186/s12967-026-08867-8 (Full text)

Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing

Abstract:

Background: SLE and ME/CFS both present significant fatigue and share immune dysregulation. The mechanisms underlying fatigue in these disorders remain unclear, and there are no standardized treatments. This study aims to explore shared mechanisms and predict potential therapeutic drugs for fatigue in SLE and ME/CFS.

Methods: Genes associated with SLE and ME/CFS were collected from disease target and clinical sample databases to identify overlapping genes. Bioinformatics analyses, including GO, KEGG, PPI network construction, and key target identification, were performed. ROC curve and correlation analysis of key targets, along with single-cell clustering, were conducted to validate their expression in different cell types. Additionally, an inflammation model was established using THP-1 cells to simulate monocyte activation in both diseases in vitro, and RT-qPCR was used to validate the expression of the key targets. A TF-mRNA-miRNA co-regulatory network was constructed, followed by drug prediction and molecular docking.

Results: Fifty-eight overlapping genes were identified, mainly involved in innate immunity and inflammation. Five key targets were identified (IL1β, CCL2, TLR2, STAT1, IFIH1). Single-cell sequencing revealed that monocytes are enriched with these targets. RT-qPCR confirmed significant upregulation of these targets in the model group. A co-regulatory network was constructed, and ten potential drugs, including suloctidil, N-Acetyl-L-cysteine, simvastatin, ACMC-20mvek, and camptothecin, were predicted. Simvastatin and camptothecin showed high affinity for the key targets.

Conclusion: SLE and ME/CFS share immune and inflammatory pathways. The identified key targets are predominantly enriched in monocytes at the single-cell level, suggesting that classical monocytes may be crucial in linking inflammation and fatigue. RT-qPCR confirmed upregulation in activated monocytes. The TF-mRNA-miRNA network provides a foundation for future research, and drug prediction suggests N-Acetyl-L-cysteine and camptothecin as potential therapies.

Source: Zheng D, Li X, Wang P, Zhu Q, Huang Z, Zhao T. Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing. Front Immunol. 2025 Jan 7;15:1440922. doi: 10.3389/fimmu.2024.1440922. PMID: 39845969; PMCID: PMC11752880. https://pmc.ncbi.nlm.nih.gov/articles/PMC11752880/ (Full text)