B Cell, Th17, and Neutrophil Related Cerebrospinal Fluid Cytokine/Chemokines Are Elevated in MOG Antibody Associated Demyelination

PLoS One. 2016 Feb 26;11(2):e0149411. doi: 10.1371/journal.pone.0149411. eCollection 2016.

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.

Aim: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autoantibodies / blood
  • B-Lymphocytes / metabolism*
  • Brain / immunology
  • Brain / metabolism
  • Brain / pathology
  • Chemokines / cerebrospinal fluid
  • Chemokines / metabolism*
  • Child
  • Child, Preschool
  • Cytokines / cerebrospinal fluid
  • Cytokines / metabolism*
  • Demyelinating Diseases / immunology
  • Demyelinating Diseases / metabolism*
  • Demyelinating Diseases / pathology
  • Encephalomyelitis, Acute Disseminated / immunology
  • Encephalomyelitis, Acute Disseminated / metabolism
  • Encephalomyelitis, Acute Disseminated / pathology
  • Female
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Myelin-Oligodendrocyte Glycoprotein / immunology*
  • Myelitis, Transverse / immunology
  • Myelitis, Transverse / metabolism
  • Myelitis, Transverse / pathology
  • Neutrophils / metabolism*
  • Th17 Cells / metabolism*

Substances

  • Autoantibodies
  • Chemokines
  • Cytokines
  • Myelin-Oligodendrocyte Glycoprotein

Grant support

This work was supported by a scholarship from the Petre Foundation, an Australian Postgraduate award, and Multiple Sclerosis Research Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.