Autoimmunity against fibrinogen mediates inflammatory arthritis in mice

Peggy P. Ho, Lowen Y. Lee, Xiaoyan Zhao, Beren H. Tomooka, Ricardo T. Paniagua, Orr Sharpe, Maya J. BenBarak, Piyanka E. Chandra, Wolfgang Hueber, Lawrence Steinman, William H. Robinson

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Rheumatoid arthritis (RA) is an autoimmune synovitis characterized by the presence of anticitrullinated protein Abs, although the exact targets and role of anticitrullinated protein autoimmunity in the pathogenesis of RA remain to be defined. Fibrinogen, which can be citrullinated, has recently emerged as a candidate autoantigen. To determine whether autoimmunity against fibrinogen can mediate inflammatory arthritis, we immunized a variety of common mouse strains with fibrinogen and found that DBA/1 and SJL mice developed an inflammatory and erosive arthritis. Mice with fibrinogen-induced arthritis (FIA) possess fibrinogen-reactive T cells that produce the proinflammatory cytokines IL-6, IL-17, TNF-α, and IFN-γ. FIA can be adoptively transferred with either plasma or fibrinogen-specific T cells from diseased mice. Mice with FIA possess rheumatoid factor, circulating immune complexes, and anticyclic citrullinated peptide Abs, all of which are characteristic of human RA. These observations demonstrate that fibrinogen is arthritogenic in mice and that the pathogenesis of FIA is mediated by both autoantibodies and fibrinogen-reactive T cells.

Original languageEnglish (US)
Pages (from-to)379-390
Number of pages12
JournalJournal of Immunology
Volume184
Issue number1
DOIs
StatePublished - Jan 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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