CSF cytokine profile in MOG-IgG+ neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications

J Neurol Neurosurg Psychiatry. 2018 Sep;89(9):927-936. doi: 10.1136/jnnp-2018-317969. Epub 2018 Jun 6.

Abstract

Objective: To evaluate cerebrospinal fluid (CSF) cytokine profiles in myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG+) disease in adult and paediatric patients.

Methods: In this cross-sectional study, we measured 27 cytokines in the CSF of MOG-IgG+ disease in acute phase before treatment (n=29). The data were directly compared with those in aquaporin-4 antibody-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) (n=20), multiple sclerosis (MS) (n=20) and non-inflammatory controls (n=14).

Results: In MOG-IgG+ disease, there was no female preponderance and the ages were younger (mean 18 years, range 3-68; 15 were below 18 years) relative to AQP4-IgG+ NMOSD (41, 15-77) and MS (34, 17-48). CSF cell counts were higher and oligoclonal IgG bands were mostly negative in MOG-IgG+ disease and AQP4-IgG+ NMOSD compared with MS. MOG-IgG+ disease had significantly elevated levels of interleukin (IL)-6, IL-8, granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor, interferon-γ, IL-10, IL-1 receptor antagonist, monocyte chemotactic protein-1 and macrophage inflammatory protein-1α as compared with MS. No cytokine in MOG-IgG+ disease was significantly different from AQP4-IgG+ NMOSD. Moreover many elevated cytokines were correlated with each other in MOG-IgG+ disease and AQP4-IgG+ NMOSD but not in MS. No difference in the data was seen between adult and paediatric MOG-IgG+ cases.

Conclusions: The CSF cytokine profile in the acute phase of MOG-IgG+ disease is characterised by coordinated upregulation of T helper 17 (Th17) and other cytokines including some Th1-related and regulatory T cells-related ones in adults and children, which is similar to AQP4-IgG+ NMOSD but clearly different from MS. The results suggest that as with AQP4-IgG+ NMOSD, some disease-modifying drugs for MS may be ineffective in MOG-IgG+ disease while they may provide potential therapeutic targets.

Keywords: aquaporin-4-IgG; cytokine profile; demyelinating disease; multiple sclerosis; myelin oligodendrocyte glycoprotein-IgG; neuromyelitis optica spectrum disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aquaporin 4 / cerebrospinal fluid*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Cytokines / cerebrospinal fluid*
  • Female
  • Humans
  • Immunoglobulin G / cerebrospinal fluid*
  • Male
  • Middle Aged
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / therapy
  • Myelin-Oligodendrocyte Glycoprotein / cerebrospinal fluid*
  • Neuromyelitis Optica / cerebrospinal fluid*
  • Young Adult

Substances

  • Aquaporin 4
  • Cytokines
  • Immunoglobulin G
  • Myelin-Oligodendrocyte Glycoprotein