title: B Cell, Th17, and Neutrophil Related Cerebrospinal Fluid Cytokine/Chemokines Are Elevated in MOG Antibody Associated Demyelination.
abstract: BACKGROUND
  Myelin oligodendrocyte glycoprotein antibody (MOG Ab) associated demyelination represents a subgroup of autoimmune demyelination that is separate from multiple sclerosis and aquaporin 4 IgG-positive NMO, and can have a relapsing course. Unlike NMO and MS, there is a paucity of literature on immunopathology and CSF cytokine/chemokines in MOG Ab associated demyelination.
  
  
  OBJECTIVE
  To study the differences in immunopathogenesis based on cytokine/chemokine profile in MOG Ab-positive (POS) and -negative (NEG) groups.
  
  
  METHODS
  We measured 34 cytokines/chemokines using multiplex immunoassay in CSF collected from paediatric patients with serum MOG Ab POS [acute disseminated encephalomyelitis (ADEM = 8), transverse myelitis (TM = 2) n = 10] and serum MOG Ab NEG (ADEM = 5, TM = 4, n = 9) demyelination. We generated normative data using CSF from 20 non-inflammatory neurological controls.
  
  
  RESULTS
  The CSF cytokine and chemokine levels were higher in both MOG Ab POS and MOG Ab NEG demyelination groups compared to controls. The CSF in MOG Ab POS patients showed predominant elevation of B cell related cytokines/chemokines (CXCL13, APRIL, BAFF and CCL19) as well as some of Th17 related cytokines (IL-6 AND G-CSF) compared to MOG Ab NEG group (all p<0.01). In addition, patients with elevated CSF MOG antibodies had higher CSF CXCL13, CXCL12, CCL19, IL-17A and G-CSF than patients without CSF MOG antibodies.
  
  
  CONCLUSIONS
  Our findings suggest that MOG Ab POS patients have a more pronounced CNS inflammatory response with elevation of predominant humoral associated cytokines/chemokines, as well as some Th 17 and neutrophil related cytokines/chemokines suggesting a differential inflammatory pathogenesis associated with MOG antibody seropositivity. This cytokine/chemokine profiling provides new insight into disease pathogenesis, and improves our ability to monitor inflammation and response to treatment. In addition, some of these molecules may represent potential immunomodulatory targets.
authors.affiliation: Neuroimmunology group, Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, University of Sydney, Sydney, NSW, Australia.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Kothur
authors.affiliation: Department of Clinical Immunology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: Wienholt
authors.affiliation: Neuroimmunology group, Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, University of Sydney, Sydney, NSW, Australia.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Tantsis
authors.affiliation: Department of Biochemistry, The Children's Hospital at Westmead, Sydney, NSW, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Earl
authors.affiliation: Department of Biochemistry, The Children's Hospital at Westmead, Sydney, NSW, Australia.
authors.forename: Sushil
authors.initials: S
authors.lastname: Bandodkar
authors.affiliation: Department of Medical Imaging, The Children's Hospital at Westmead, Sydney, NSW, Australia.
authors.forename: Kristina
authors.initials: K
authors.lastname: Prelog
authors.affiliation: Neuroimmunology group, Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, University of Sydney, Sydney, NSW, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: Tea
authors.affiliation: Neuroimmunology group, Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, University of Sydney, Sydney, NSW, Australia.
authors.forename: Sudarshini
authors.initials: S
authors.lastname: Ramanathan
authors.affiliation: Neuroimmunology group, Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, University of Sydney, Sydney, NSW, Australia.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Brilot
authors.affiliation: Neuroimmunology group, Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, University of Sydney, Sydney, NSW, Australia.
authors.forename: Russell C
authors.initials: RC
authors.lastname: Dale
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000378:metabolism*; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018925:Chemokines / Q000134:cerebrospinal fluid / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000134:cerebrospinal fluid / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004673:Encephalomyelitis, Acute Disseminated / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*; D009188:Myelitis, Transverse / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism*; D058504:Th17 Cells / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D018925:Chemokines; D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein