Change in autoantibody and cytokine responses during the evolution of neuromyelitis optica in patients with systemic lupus erythematosus: A preliminary study

Mult Scler. 2016 Aug;22(9):1192-201. doi: 10.1177/1352458515613165. Epub 2015 Oct 29.

Abstract

Background: Neuromyelitis optica (NMO)-systemic lupus erythematosus (SLE) association is a rare condition characterized by multiple autoantibodies.

Objective: To examine if, during the evolution of NMO, anti-AQP4 responses are part of polyclonal B cell activation, and if T cell responses contribute.

Methods: In 19 samples of six patients who developed NMO during SLE, we examined the correlation of AQP4-IgG1 and IgM with (i) anti-MOG IgG and IgM, (ii) anti-nuclear, anti-nucleosome and anti-dsDNA IgG antibodies, (iii) cytokines and chemokines in the serum and (iv) longitudinal relation to NMO relapses/remission.

Results: AQP4-IgG1 was present 1-2-5 years before the first NMO relapse. During relapse, AQP4-IgG1, ANA, anti-dsDNA and anti-nucleosome antibodies were elevated. Anti-MOG IgG/IgM and AQP4-IgM antibodies were not detected. AQP4-IgG1 antibodies correlated with concentration of anti-nucleosome, IFN-γ,interferon-gamma-induced CCL10/IP-10 and CCL17/TARC (p<0.05, respectively). CCL17/TARC correlated with levels of anti-nucleosome and anti-dsDNA (p<0.05, respectively). Compared to healthy subjects, concentration of IFN-γ and CCL17/TARC was higher in NMO/SLE (p<0.05).

Conclusions: AQP4-IgG1 antibodies are present in the sera years before the first NMO attack in patients with SLE; elevation of anti-AQP4 is part of a polyclonal B cell response during NMO relapses; in spite of multiple autoantibodies in the serum, MOG antibodies were not present; Th1 responses accompany autoantibody responses in NMO/SLE.

Keywords: AQP4; IL-17; IP-10; SLE; Th1; Th17; myelin oligodendrocyte glycoprotein.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aquaporin 4 / immunology*
  • Autoantibodies / blood*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Biomarkers / blood
  • Child
  • Cytokines / blood*
  • Female
  • Humans
  • Immunoglobulin G / blood*
  • Immunoglobulin M / blood*
  • Immunosuppressive Agents / therapeutic use
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / immunology*
  • Lymphocyte Activation
  • Middle Aged
  • Neuromyelitis Optica / blood
  • Neuromyelitis Optica / diagnosis
  • Neuromyelitis Optica / drug therapy
  • Neuromyelitis Optica / immunology*
  • Preliminary Data
  • Recurrence
  • Remission Induction
  • Retrospective Studies
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • AQP4 protein, human
  • Aquaporin 4
  • Autoantibodies
  • Biomarkers
  • Cytokines
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunosuppressive Agents