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Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival
Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. National Bioinformatics Infrastructure Sweden (NBIS), Sweden.
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Number of Authors: 9
2017 (English)In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 15, 102Article in journal (Refereed) Published
Abstract [en]

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 Nor-CAPITAL 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.

Place, publisher, year, edition, pages
2017. Vol. 15, 102
Keyword [en]
Chronic fatigue syndrome, Adolescent, Gene expression, Inflammation, B cell differentiation, B cell survival
National Category
Clinical Laboratory Medicine Immunology in the medical area
Identifiers
URN: urn:nbn:se:su:diva-144839DOI: 10.1186/s12967-017-1201-0ISI: 000402015200002PubMedID: 28494812OAI: oai:DiVA.org:su-144839DiVA: diva2:1120127
Available from: 2017-07-05 Created: 2017-07-05 Last updated: 2017-07-05Bibliographically approved

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Lindvall, Jessica M.
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Science for Life Laboratory (SciLifeLab)Department of Biochemistry and Biophysics
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