Ficolin-1 is a promising therapeutic target for autoimmune diseases

Int Immunol. 2019 Feb 6;31(1):23-32. doi: 10.1093/intimm/dxy056.

Abstract

Previously, we reported that mRNA expression of ficolin-1 (FCN1), a component of the complement lectin pathway, is elevated in peripheral blood mononuclear cells of patients with vasculitis syndrome, and that FCN1-positive cells infiltrate into inflamed regions in patient specimens. In addition, we reported that the serum FCN1 concentration is elevated in patients with Kawasaki disease (KD), a pediatric vasculitis, but dramatically decreases after intravenous immunoglobulin (IVIG) treatment. Furthermore, we showed that FCN1 binds to IgG1 in a pull-down assay. These results suggested that removal of FCN1 may be a therapeutic mechanism of IVIG. In this study, we prepared anti-FCN1 monoclonal antibody (mAb) and examined its therapeutic potential in mice treated with Candida albicans water-soluble fraction (CAWS), which induces KD-like vasculitis in the coronary artery. Indeed, treatment with anti-FCN1 mAb decreased the histological score of vasculitis (P = 0.03). To investigate the role of FCN1, we assessed blood samples of patients with various autoimmune diseases and demonstrated that serum levels of FCN1 were elevated not only in patients with vasculitis, but also in those with rheumatoid arthritis. Additionally, FCN1-targeted treatment of a mouse model of arthritis [collagen antibody-induced arthritis (CAIA)] revealed that administration of anti-FCN1 mAb ameliorated symptoms of arthritis (P < 0.01). These results suggest that FCN1 is involved in the pathogenesis of autoimmune diseases, and that targeting FCN1 represents a promising strategy for treating these diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / etiology*
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • Biomarkers
  • Complement System Proteins / immunology
  • Complement System Proteins / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Lectins / antagonists & inhibitors
  • Lectins / immunology*
  • Lectins / metabolism
  • Male
  • Mice
  • Middle Aged
  • Molecular Targeted Therapy
  • Vasculitis / etiology
  • Vasculitis / metabolism
  • Vasculitis / pathology

Substances

  • Antibodies, Monoclonal
  • Biomarkers
  • Lectins
  • ficolin
  • Complement System Proteins