Anti-citrullinated collagen type I antibody is a target of autoimmunity in rheumatoid arthritis

Biochem Biophys Res Commun. 2005 Jul 29;333(2):418-26. doi: 10.1016/j.bbrc.2005.05.137.

Abstract

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, but its autoimmune mechanisms are not clearly understood. Recently, anti-citrullinated peptide antibodies have been specifically observed in sera of RA patients. Furthermore, we identified RA-susceptible variant in a gene encoding citrullinating enzyme, peptidylarginine deiminase type 4 (PADI4). Therefore, we hypothesized that proteins which are modified in RA synovium by PADI4 act as autoantigens. Subsequently, we obtained human collagen type I (huCI) as one of the autoantigens using a RA synoviocyte cDNA library by immunoscreening. We also investigated that the levels of anti-citrullinated huCI were significantly higher in RA patient sera than in normal control sera with high specificity (99%) and positively correlated with the levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies. We concluded that huCI is a novel substrate protein of PADIs and that citrullinated huCI is a candidate autoantigen of RA.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / immunology*
  • Autoimmunity / immunology*
  • Citrulline / immunology
  • Collagen Type I / immunology*
  • Female
  • Humans
  • Hydrolases / immunology*
  • Male
  • Middle Aged
  • Protein-Arginine Deiminases
  • Synovial Membrane / immunology*

Substances

  • Autoantibodies
  • Collagen Type I
  • Citrulline
  • Hydrolases
  • Protein-Arginine Deiminases