A novel autoantibody against moesin in the serum of patients with MPO-ANCA-associated vasculitis

Nephrol Dial Transplant. 2014 Jun;29(6):1168-77. doi: 10.1093/ndt/gft469. Epub 2013 Dec 5.

Abstract

Background: Antineutrophil cytoplasmic autoantibody (ANCA) directed against myeloperoxidase (MPO), a diagnostic criterion in MPO-ANCA-associated vasculitis (MPO-AAV), does not always correlate with disease activity. Here, we detected autoantibodies against moesin, which was located on the surface of stimulated endothelial cells, in the serum of patients.

Methods: The anti-moesin autoantibody titer was evaluated by ELISA. Seventeen kinds of cytokines/chemokines were measured by a Bio-Plex system.

Results: Serum creatinine in the anti-moesin autoantibody-positive group was higher than that in the negative group. Additionally, interferon (IFN)-γ, macrophage chemotactic peptide-1 (MCP-1), interleukin (IL)-2, IL-7, IL-12p70, IL-13, granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor were significantly higher in the positive group. Furthermore, IL-7 and IL-12p70 levels correlated with the anti-moesin autoantibody titer. Based on these findings and the binding of anti-moesin IgG to neutrophils and monocytes, we detected the secretion of cytokines/chemokines such as IFN-γ, MCP-1 and GM-CSF from these cells.

Conclusions: The anti-moesin autoantibody existed in the serum of patients with MPO-AAV and was associated with the production of inflammatory cytokines/chemokines targeting neutrophils with a cytoplasmic profile, which suggests that the anti-moesin autoantibody has the possibility to be a novel autoantibody developing vasculitis via neutrophil and endothelial cell activation.

Keywords: autoantibodies; glomerulonephritis; moesin; myeloperoxidase; neutrophil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / immunology*
  • Autoantibodies / blood*
  • Chemokines / metabolism
  • Endothelium, Vascular / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Granulocyte Colony-Stimulating Factor / blood
  • Humans
  • Interleukins / immunology
  • Macrophage Inflammatory Proteins / blood
  • Male
  • Microfilament Proteins / immunology*
  • Middle Aged
  • Peroxidase / immunology*

Substances

  • Autoantibodies
  • Chemokines
  • Interleukins
  • Macrophage Inflammatory Proteins
  • Microfilament Proteins
  • Granulocyte Colony-Stimulating Factor
  • moesin
  • Peroxidase