Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival
Open accessAbstract
BACKGROUND: Chronic fatigue syndrome (CFS) is a prevalent and disabling condition affecting adolescents. The pathophysiology is poorly understood, but immune alterations might be an important component. This study compared whole blood gene expression in adolescent CFS patients and healthy controls, and explored associations between gene expression and neuroendocrine markers, immune markers and clinical markers within the CFS group. METHODS: CFS patients (12-18 years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied, requiring 3 months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Healthy controls having comparable distribution of gender and age were recruited from local schools. Whole blood samples were subjected to RNA sequencing. Immune markers were blood leukocyte counts, plasma cytokines, serum C-reactive protein and immunoglobulins. Neuroendocrine markers encompassed plasma and urine levels of catecholamines and cortisol, as well as heart rate variability indices. Clinical markers consisted of questionnaire scores for symptoms of post-exertional malaise, inflammation, fatigue, depression and trait anxiety, as well as activity recordings. RESULTS: A total of 29 CFS patients and 18 healthy controls were included. We identified 176 genes as differentially expressed in patients compared to controls, adjusting for age and gender factors. Gene set enrichment analyses suggested impairment of B cell differentiation and survival, as well as enhancement of innate antiviral responses and inflammation in the CFS group. A pattern of co-expression could be identified, and this pattern, as well as single gene transcripts, was significantly associated with indices of autonomic nervous activity, plasma cortisol, and blood monocyte and eosinophil counts. Also, an association with symptoms of post-exertional malaise was demonstrated. CONCLUSION: Adolescent CFS is characterized by differential gene expression pattern in whole blood suggestive of impaired B cell differentiation and survival, and enhanced innate antiviral responses and inflammation. This expression pattern is associated with neuroendocrine markers of altered HPA axis and autonomic nervous activity, and with symptoms of post-exertional malaise. Trial registration Clinical Trials NCT01040429.
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Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop?
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Deep phenotyping of myalgic encephalomyelitis/chronic fatigue syndrome in Japanese population
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Pharmaceutical Interventions in Chronic Fatigue Syndrome: A Literature-based Commentary
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Skewing of the B cell receptor repertoire in myalgic encephalomyelitis/chronic fatigue syndrome
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Plasma cytokine levels reveal deficiencies in IL-8 and gamma interferon in Long-COVIDPreprint
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Study on the Relationship between the miRNA-centered ceRNA Regulatory Network and Fatigue
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Self-citationTransforming Growth Factor Beta (TGF-β) in Adolescent Chronic Fatigue Syndrome
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Self-citationEvaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects
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A Clinically Validated Human Capillary Blood Transcriptome Test For Global Systems Biology Studies
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Lessons From Heat Stroke for Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
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Bulk RNA sequencing for analysis of post COVID-19 condition in adolescents and young adults
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What Causes ME/CFS: The Role of the Dysfunctional Immune System and Viral Infections
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Batch correction of genomic data in chronic fatigue syndrome using CMA-ES
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- Authors
- Nguyen, C. B., Alsøe, L., Lindvall, J. M., Sulheim, D., Fagermoen, E., Winger, A., Kaarbø, M., Nilsen, H., & Wyller, V. B.
- Affiliations
- University of Oslo (NO)
- Stockholm University (SE)
- Oslo University Hospital (NO)
- OsloMet – Oslo Metropolitan University (NO)
- Corresponding author
- Wyller, Vegard Bruun
- ORCID
- Venue
- Journal of Translational Medicine
- Published
- 2017-05-11
- Volume
- 15
- Issue
- 1
- Pages
- 102-102
- ISSN
- 1479-5876 (ISSN-L)
- PMC
- PMC5426002
- OpenAlex
- W2612662388
- Cited by
- 59
- References
- 87
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 4 · 2022: 7 · 2021: 12 · 2020: 9 · 2019: 9 · 2018: 3 · 2017: 2
- FWCI
- 5.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Translational Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- BIBSYS Brage (BIBSYS (Norway)) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- Universitetet i Oslo
- Norges Forskningsråd
- Helse Sør-Øst RHF
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Keywords
- chronic fatigue syndrome, adolescents, whole blood gene expression, B cell differentiation, B cell survival, antiviral innate immunity, inflammation, hypothalamic-pituitary-adrenal axis, autonomic nervous system activity, cortisol, catecholamines, heart rate variability, post-exertional malaise, monocytes, eosinophils
- MeSH terms
- Adolescent, B-Lymphocytes, Cell Differentiation, Cell Survival, Child, Cross-Sectional Studies, Female, Gene Expression Regulation, Humans, Male, RNA, Messenger, Statistics as Topic, Biomarkers, Fatigue Syndrome, Chronic, Cluster Analysis, Case-Control Studies, Gene Expression Profiling
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