4.6 Article

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

Journal

NEPHROLOGY DIALYSIS TRANSPLANTATION
Volume 29, Issue 6, Pages 1168-1177

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/ndt/gft469

Keywords

autoantibodies; glomerulonephritis; moesin; myeloperoxidase; neutrophil

Funding

  1. Ministry of Health, Labour and Welfare of Japan [H21-S-I-004]
  2. Grants-in-Aid for Scientific Research [23510244, 24659268] Funding Source: KAKEN

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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 autoantibodypositive group was higher than that in the negative group. Additionally, interferon (IFN)-., 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-., 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.

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