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Arthritis induced by systemic autoimmunity against glucose-6-phosphate isomerase in normal mice

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The antigens that trigger the pathogenic immune response in rheumatoid arthritis remain unknown. Until recently it was assumed that joint-specific antigens were the targets of arthritogenic T lymphocytes and B lymphocytes in rheumatoid arthritis. Consequently, murine models of arthritis are induced by immunization with either joint-specific antigens such as type II collagen or microbial products such as streptococcal cell wall. In the K/BxN T-cell receptor transgenic mouse model, arthritis is caused by a systemic autoimmune response to the ubiquitously expressed glycolytic enzyme glucose-6-phosphate isomerase (G6PI). More recently it was shown that G6PI immunization induces severe symmetrical peripheral polyarthritis in genetically unaltered DBA/I or SJL mice [1, 2]. T cells are indispensable for both the induction and the effector phase of G6PI-induced arthritis. Arthritis is cured by depletion of CD4 cells. In contrast, antibodies and FcγR effector cells are necessary but not sufficient for G6PI-induced arthritis in genetically unaltered mice [1]. Both the induction and effector phase of arthritis induced by a systemic autoimmune response can be dissected and preventive and therapeutic strategies evaluated in this model.

References

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    Schubert D, Maier B, Morawietz L, Krenn V, Kamradt T: Immunization with glucose-6-phosphate isomerase induces T-cell dependent peripheral polyarthritis in genetically unaltered mice. J Immunol. 2004, 172: 4503-4509.

  2. 2.

    Bockermann R, Schubert D, Kamradt T, Holmdahl R: Induction of a B cell dependent chronic arthritis with glucose 6 phosphate isomerase. Arthritis Res Therapy. 2005, 7: R1316-R1324. 10.1186/ar1829.

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Kamradt, T., Bruns, L., Frey, O. et al. Arthritis induced by systemic autoimmunity against glucose-6-phosphate isomerase in normal mice. Arthritis Res Ther 9, P12 (2007). https://doi.org/10.1186/ar2238

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Keywords

  • Rheumatoid Arthritis
  • Arthritis
  • Transgenic Mouse Model
  • Glycolytic Enzyme
  • Microbial Product