Different amounts of protein-bound citrulline and homocitrulline in foot joint tissues of a patient with anti-citrullinated protein antibody positive erosive rheumatoid arthritis

J Transl Med. 2013 Sep 23;11:224. doi: 10.1186/1479-5876-11-224.


Background: Antibodies binding to citrullinated proteins are a frequent finding in rheumatoid arthritis patients and may precede the onset of clinical symptoms several years. The antibodies are a predisposing factor for bone erosions but their origin is unknown. In this study we analyze in detail the levels of protein bound citrulline and homocitrulline in several tissue samples of a single erosive arthritic surgery patient.

Methods: Serum antibodies binding to CCP, MCV and citrulline- or homocitrulline-containing type I and II collagen carboxytelopeptides were measured. Tissue samples of a single RA patient, taken in two separate operations performed with two-year time span were hydrolyzed and analyzed for citrulline and homocitrulline content by HPLC.

Results: Protein-bound citrulline and homocitrulline were found in several joint tissues of a RA patient with ACPA-positive erosive disease. The amount of homocitrulline stayed relatively constant between the different tissues. The amount of citrulline in erosive tissue was 3-times higher than in non-erosive tissue in the first operation. In the samples of the second operation 3-4-times higher mean amounts of citrulline were found in two out of the six tissues investigated.

Conclusions: Homocitrulline is present in rheumatoid nodule together with citrulline. There is more variation in the amount of citrulline than in the amount of homocitrulline between the tissues. The tissue sample containing the most citrulline was the most erosive.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / surgery
  • Autoantibodies / immunology*
  • Chromatography, High Pressure Liquid
  • Citrulline / analogs & derivatives*
  • Citrulline / immunology
  • Female
  • Foot Joints / diagnostic imaging
  • Foot Joints / immunology*
  • Foot Joints / pathology
  • Foot Joints / surgery
  • Humans
  • Middle Aged
  • Protein Binding
  • Radiography


  • Autoantibodies
  • homocitrulline
  • Citrulline