title: Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations.
abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a persistent and debilitating disorder marked by cognitive and sensory dysfunction and unexplained physical fatigue. Classically, cases present after a prodrome consistent with infection; however, some cases are atypical and have a different presentation and comorbidities that pose challenges for differential diagnosis. We analyzed cerebrospinal fluid (CSF) from 32 cases with classical ME/CFS and 27 cases with atypical ME/CFS using a 51-plex cytokine assay. Atypical subjects differed in cytokine profiles from classical subjects. In logistic regression models incorporating immune molecules that were identified as potential predictor variables through feature selection, we found strong associations between the atypical ME/CFS phenotype and lower CSF levels of the inflammatory mediators, interleukin 17A and CXCL9. Network analysis revealed an absence of inverse inter-cytokine relationships in CSF from atypical patients, and more sparse positive intercorrelations, than classical subjects. Interleukin 1 receptor antagonist appeared to be a negative regulator in classical ME/CFS, with patterns suggestive of disturbances in interleukin 1 signaling and autoimmunity-type patterns of immune activation. Immune signatures in the central nervous system of ME/CFS patients with atypical features may be distinct from those with more typical clinical presentations.
authors.affiliation: Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY, USA.|Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hornig
authors.affiliation: Sierra Internal Medicine at Incline Village, Incline Village, NV, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Gottschalk
authors.affiliation: Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Eddy
authors.affiliation: Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY, USA.
authors.forename: X
authors.initials: X
authors.lastname: Che
authors.affiliation: Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Ukaigwe
authors.affiliation: Sierra Internal Medicine at Incline Village, Incline Village, NV, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Peterson
authors.affiliation: Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY, USA.|Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA.|Department of Neurology, College of Physicians & Surgeons, Columbia University, New York, NY, USA.|Department of Pathology and Cell Biology, College of Physicians & Surgeons, Columbia University, New York, NY, USA.
authors.forename: W I
authors.initials: WI
authors.lastname: Lipkin
mesh_terms: D000328:Adult; D002555:Cerebrospinal Fluid / Q000276:immunology*; D054370:Chemokine CXCL9 / Q000134:cerebrospinal fluid / Q000276:immunology; D016207:Cytokines / Q000134:cerebrospinal fluid* / Q000276:immunology; D003937:Diagnosis, Differential; D015673:Fatigue Syndrome, Chronic / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D054370:Chemokine CXCL9; D016207:Cytokines; C508717:IL17A protein, human; D020381:Interleukin-17