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J Transl Med. 2017 May 11;15(1):102. doi: 10.1186/s12967-017-1201-0.

Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival.

Author information

1
Department of Paediatrics and Adolescent Health, Akershus University Hospital, 1478, Lørenskog, Norway.
2
Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Oslo, Norway.
3
Institute of Clinical Medicine, Department of Clinical Molecular Biology, University of Oslo, and Akershus University Hospital, Lørenskog, Norway.
4
National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
5
Department of Paediatrics, Lillehammer County Hospital, Lillehammer, Norway.
6
Department of Anesthesiology and Critical Care, Oslo University Hospital, Oslo, Norway.
7
Institute of Nursing Sciences, Oslo and Akershus University College of Applied Sciences, Oslo, Norway.
8
Department of Microbiology, Oslo University Hospital, Oslo, Norway.
9
Department of Paediatrics and Adolescent Health, Akershus University Hospital, 1478, Lørenskog, Norway. brwylle@online.no.
10
Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Oslo, Norway. brwylle@online.no.

Abstract

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.

KEYWORDS:

Adolescent; B cell differentiation; B cell survival; Chronic fatigue syndrome; Gene expression; Inflammation

PMID:
28494812
PMCID:
PMC5426002
DOI:
10.1186/s12967-017-1201-0
[Indexed for MEDLINE]
Free PMC Article

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