Immunization with the glycolytic enzyme glucose-6-phosphate isomerase (GPI) induces peripheral polyarthritis in genetically unaltered mice
© The Author(s) 2004
Received: 16 January 2004
Published: 24 February 2004
Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology that primarily affects the joints. Recently, a T cell receptor transgenic murine model yielded novel insights. K/BxN TCR transgenic mice spontaneously develop an autoimmune arthritis that resembles human RA. Arthritis development depends on the recognition of the ubiquitously expressed glycolytic enzyme GPI by both the transgenic T cells and B lymphocytes. Here we show that immunization with heterologous GPI in adjuvant induces a symmetric polyarthritis of the small distal joints in genetically susceptible mice. The course of GPI-induced arthritis is highly predictable: clinically overt arthritis develops 9–10 days after immunization, reaches its maximum at D15 and then slowly resolves. Histologically, the disease is characterized by early synovitis followed by massive cartilage destruction and erosions of the bones and later resolution of the inflammation, fibrosis, and repair processes. Although antibody titers in susceptible and nonsusceptible mouse strains are high, transfer of purified total IgG of sick mice alone do not transfer disease. Anyway, antibodies seem to play a major role since Fc-receptor γ-chain deficient mice develop disease with a much lower frequency and reduced severity than the wild-type mice. Treatment with a depleting monoclonal anti-CD4 antibody completely prevents disease. Depletion of CD4+ T cells during disease leads to a rapid resolution of arthritis. Therefore, CD4+ T cells are important for both the induction of the disease and the effector phase. Thus, GPI-induced arthritis in normal mice bridges the gap between the transgenic K/BxN model and the highly complex human situation, thereby providing a model in which both the induction and effector phase of antigen specific arthritis can be dissected, and preventive and therapeutic strategies evaluated.