Immunization with mixed peptides derived from glucose-6-phosphate isomerase induces rheumatoid arthritis in DBA/1 mice

AIM: To establish an animal model of rheumatoid arthritis(RA) in DBA/1 mice induced by immunodominant mixed peptides derived from glucose-6-phosphate isomerase(GPI). METHODS: The DBA/1 mice were immunized with emulsified mixed peptide fragments of hGPI325-339+hGPI469-483 or single peptide hGPI325-339 in complete Freund's adjuvant by subcutaneous injection to induce the model of RA. Body weight, ankle joint symptom scores, the pathological change of the ankle joint, the levels of CD4⁺ T cells in the spleen and peripheral blood, the proportion of iNKT cells in the peripheral blood, and the levels of TNF-α and IL-6 in serum were detected to evaluate and analyze the model. RESULTS: The hind paw of the model mice appeared red swelling on the 8th day, and then aggravated gradually to the limbs. The red swelling reached peak on the 14th day, and then relieved gradually. Inflammation response dominated by lymphocytes and monocytes was observed in the ankle joint. The inflammatory effect of mixed peptides was more obvious than that of the single one(P<0.05). Compared with control group and the mice treated with single peptide, the weight gain was slow, the amount of CD4⁺ T cells in the peripheral blood and spleen were increased, the proportion of peripheral iNKT cells in the inflammatory peak was decreased(P<0.05), and the serum level of TNF-α was increased significantly(P<0.05) in the mice treated with mixed peptide fragments. CONCLUSION: The immunological characteristics of RA model induced by mixed GPI peptides in DBA/1 mice is closer to that in RA patients, especially in the immunopathology of iNKT cells. Therefore, this model can be used as a new tool for studying the mechanism and immunological intervention of RA.