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Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional..

Discussion in 'Latest ME/CFS Research' started by Kati, May 11, 2017.

  1. Kati

    Kati Patient in training

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

    Chinh Bkrong Nguyen, Lene Alsøe, Jessica M. Lindvall, Dag Sulheim, Even Fagermoen, Anette Winger, Mari Kaarbø, Hilde Nilsen and Vegard Bruun Wyller



    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.


    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.


    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.


    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
  2. A.B.

    A.B. Senior Member

    MEMum likes this.
  3. trishrhymes

    trishrhymes Senior Member

    I've only read the abstract. I don't have enough brain energy left today to wade through a very lengthy paper. Two things strike me.

    First, it's interesting that they are finding differences related to B cells, which might tie in with the Rituximab work.

    Secondly that it's a tiny sample, confounded by such a broad definition of CFS, so it's surprising they found anything. Seems a pity, when going to so much effort in analysis, to have such a small, yet broad sample.
    JaimeS and Hutan like this.
  4. Murph

    Murph :)

    Looks to me like a study that has found relatively little to report. The differential gene expression is mostly a quite minor fold change: 0.8 to 1.25. The differences in epinephrine are real but not earth shattering

    Most elements they studied were insignificantly different. :\

    Perhaps related to the patient cohort being ill defined.
  5. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    I tend to agree that nothing very specific jumps out from this. The B cell shifts could be interesting. No doubt Jo Cambridge and Fane Mensa will have a close look. But the shifts are not that big.
    JaimeS, Marky90, Hutan and 2 others like this.
  6. RogerBlack

    RogerBlack Senior Member

    Is this a worse case definition than Oxford?
    No mention of eliminating other diseases, 3 months, not 6, ...

    Unless there is pre-selection due to the referring physicians applying a more sane criteria, this seems of limited value, other than as an interesting control group.

    It would be quite valuable I suspect to look at CFS/Fatigue/Control.
    JaimeS and Manganus like this.
  7. AndyPR

    AndyPR Senior Member

  8. JaimeS

    JaimeS Senior Member

    Silicon Valley, CA
    Such a loose criteria -- just 3 months of fatigue.

    The genes look interesting, but... with such a broad criteria, I don't feel we really know who we're looking at.
    Snowdrop and RL_sparky like this.
  9. lnester7

    lnester7 Seven

    another OI on teens, question would be is the OI preexisting like predisposing to CFS (like that other study had suggested) or is it a consequence.
    JaimeS likes this.

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