Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis.

Research output: Contribution to journalArticle

Abstract

Antibodies to citrulline-modified proteins have a high diagnostic value in rheumatoid arthritis (RA). However, their biological role in disease development is still unclear. To obtain insight into this question, a panel of mouse monoclonal antibodies was generated against a major triple helical collagen type II (CII) epitope (position 359-369; ARGLTGRPGDA) with or without arginines modified by citrullination. These antibodies bind cartilage and synovial tissue, and mediate arthritis in mice. Detection of citrullinated CII from RA patients' synovial fluid demonstrates that cartilage-derived CII is indeed citrullinated in vivo. The structure determination of a Fab fragment of one of these antibodies in complex with a citrullinated peptide showed a surprising beta-turn conformation of the peptide and provided information on citrulline recognition. Based on these findings, we propose that autoimmunity to CII, leading to the production of antibodies specific for both native and citrullinated CII, is an important pathogenic factor in the development of RA.

Details

Authors
  • Hüseyin Uysal
  • Robert Bockermann
  • Nandakumar Kutty Selva
  • Bettina Sehnert
  • Estelle Bajtner
  • Ake Engström
  • Guy Serre
  • Harald Burkhardt
  • Marjolein Thunnissen
  • Rikard Holmdahl
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)449-462
JournalJournal of Experimental Medicine
Volume206
Issue number2
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Biochemistry and Structural Biology (S) (000006142), Medical Inflammation Research (013212019)

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