Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome

Hornig, Mady; Gottschalk, Gunnar; Peterson, Daniel L.; Knox, Konstance K.; Schultz, Andrew F.; Eddy, M L; Che, Xin; Lipkin, W. Ian

doi:10.1038/mp.2015.29

Cited by 82 publications

(81 citation statements)

References 49 publications

(45 reference statements)

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“…We sampled only peripheral blood and not other compartments such as cerebrospinal fluid (CSF). Cytokine studies in the CSF of ME/CFS patients have reported abnormalities even though the sample size has been modest and simultaneous serum samples were not analyzed (54,55). In one study, a diathesis to allergic and inflammatory responses in CSF, similar to some of our findings, were found in these patients (54,55).…”

Section: Discussionsupporting

confidence: 66%

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Montoya

Holmes

Anderson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

296

265

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Although some signs of inflammation have been reported previously in patients with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), the data are limited and contradictory. High-throughput methods now allow us to interrogate the human immune system for multiple markers of inflammation at a scale that was not previously possible. To determine whether a signature of serum cytokines could be associated with ME/CFS and correlated with disease severity and fatigue duration, cytokines of 192 ME/CFS patients and 392 healthy controls were measured using a 51-multiplex array on a Luminex system. Each cytokine’s preprocessed data were regressed on ME/CFS severity plus covariates for age, sex, race, and an assay property of newly discovered importance: nonspecific binding. On average, TGF-β was elevated (P = 0.0052) and resistin was lower (P = 0.0052) in patients compared with controls. Seventeen cytokines had a statistically significant upward linear trend that correlated with ME/CFS severity: CCL11 (Eotaxin-1), CXCL1 (GROα), CXCL10 (IP-10), IFN-γ, IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-α. Of the 17 cytokines that correlated with severity, 13 are proinflammatory, likely contributing to many of the symptoms experienced by patients and establishing a strong immune system component of the disease. Only CXCL9 (MIG) inversely correlated with fatigue duration.

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Section: Discussionsupporting

confidence: 66%

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Montoya

Holmes

Anderson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

296

265

View full text Add to dashboard Cite

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“…A decrease in IL-10 favors an increase in pro-inflammatory responses, and this may increase the prevalence of Th1-like cytokines. Importantly, we and others have reported significant reductions in IL-10 from CFS/ME patients 58,59…”

Section: Discussionsupporting

confidence: 50%

Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients

Chacko

Staines

Johnston

et al. 2016

Gene�Regul Syst Bio

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BACKGROUNDThe etiology and pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) are unknown. However, natural killer (NK) cell dysfunction, in particular reduced NK cytotoxic activity, is a consistent finding in CFS/ME patients. Previous research has reported significant changes in intracellular mitogen-activated protein kinase pathways from isolated NK cells. The purpose of this present investigation was to examine whether protein kinase genes have a role in abnormal NK cell intracellular signaling in CFS/ME.METHODMessenger RNA (mRNA) expression of 528 protein kinase genes in isolated NK cells was analyzed (nCounter GX Human Kinase Kit v2 (XT); NanoString Technologies) from moderate (n = 11; age, 54.9 ± 10.3 years) and severe (n = 12; age, 47.5 ± 8.0 years) CFS/ME patients (classified by the 2011 International Consensus Criteria) and nonfatigued controls (n = 11; age, 50.0 ± 12.3 years).RESULTSThe expression of 92 protein kinase genes was significantly different in the severe CFS/ME group compared with nonfatigued controls. Among these, 37 genes were significantly upregulated and 55 genes were significantly downregulated in severe CFS/ME patients compared with nonfatigued controls.CONCLUSIONSIn severe CFS/ME patients, dysfunction in protein kinase genes may contribute to impairments in NK cell intracellular signaling and effector function. Similar changes in protein kinase genes may be present in other cells, potentially contributing to the pathomechanism of this illness.

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“…We used NodeXL to build within group analyte network diagrams (Hornig et al , 2015; Smith et al , 2010). Network analysis was utilized to understand the relationships between analytes and identify connection patterns.…”

Section: Methodsmentioning

confidence: 99%

Angiogenic and immune signatures in plasma of young relatives at familial high-risk for psychosis and first-episode patients: A preliminary study

Lizano

Keshavan

Tandon

et al. 2016

Schizophrenia Research

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Schizophrenia (SZ) is a heterogeneous disorder that presents in adolescence, persists into adulthood, and has many clinical features. Recent evidence suggests that abnormalities in inflammatory, neurotrophic, and angiogenic processes may play a role in the etiology of SZ. The identification of molecular biomarkers early in the course of disease is crucial to transforming diagnostic and therapeutic avenues. We investigated 14 molecular analytes focusing on inflammatory, neurotrophic and angiogenic pathways from the plasma of antipsychotic-naïve familial high risk for SZ (FHR; n=35) and first-episode psychosis (FEP; n=45) subjects, in comparison to healthy controls (HC, n=39). We identified distinct alterations in molecular signatures in young relatives at FHR for SZ prior to psychosis onset and FEP subjects. Firstly, the expression of soluble fms-like tyrosine kinase (sFlt-1), an anti-angiogenic factor that binds vascular endothelial growth factor (VEGF), was significantly increased in the FHR group compared to HC, but not in FEP. Secondly, interferon gamma (IFNγ) was significantly reduced in the FEP group compared to HC. Thirdly, network analysis revealed a positive correlation between sFlt-1 and VEGF, suggesting an activation of the angiogenic cascade in the FHR group, which persists in FEP. Our results indicate an angiogenesis and immunological dysfunction early in the course of disease, shifting the balance towards anti-angiogenesis and inflammation.

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Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome

Cited by 82 publications

References 49 publications

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients

Angiogenic and immune signatures in plasma of young relatives at familial high-risk for psychosis and first-episode patients: A preliminary study

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