CENP-O, a protein localized at the centromere throughout the cell cycle, is a novel target antigen in systemic sclerosis

J Rheumatol. 2009 Apr;36(4):781-6. doi: 10.3899/jrheum.080726. Epub 2009 Mar 13.

Abstract

Objective: CENP-A, -B, and -C are major centromere components and the main targets of anticentromere antibodies (ACA). Many other proteins are also assembled around CENP-A nucleosomes in interphase nuclei to form the interphase centromere complex (ICEN). The CENP-O protein is a component of the ICEN that localizes at the centromere throughout the cell cycle. We investigated whether CENP-O is also targeted by sera from patients with systemic autoimmune diseases.

Methods: Sera from 114 patients with ACA and 142 patients without ACA were analyzed. Western blotting and an ELISA with bacterially expressed recombinant CENP-O protein were performed to screen for the presence of anti-CENP-O antibodies. In addition, anti-CENP-O antibody-positive sera were tested by Western blotting HeLa cell extracts to examine reactivity with the major centromere antigens.

Results: Four female patients with ACA had anti-CENP-O antibodies. There was no correlation of anti-CENP-O antibodies with specific clinical features or other serological features. However, one of the 4 patients, who showed a unique clinical course of scleroderma, had sera with markedly high reactivity to CENP-O.

Conclusion: CENP-O protein is a novel centromere antigen that is recognized by a very minor population of ACA-positive patients with scleroderma. Because CENP-O is an ICEN component, ICEN may be a large antigenic structure in systemic autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens / immunology*
  • Autoantibodies / immunology*
  • Cell Cycle / physiology*
  • Centromere / metabolism*
  • Chromosomal Proteins, Non-Histone / immunology*
  • DNA-Binding Proteins / immunology*
  • Female
  • HeLa Cells
  • Humans
  • Middle Aged
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / physiopathology

Substances

  • Antigens
  • Autoantibodies
  • CENPO protein, human
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins