The Function And Mechanism Of Costimulatory Molecules OX40/OX40l Expression In Immunological Pathogenesis Of Graves’ Disease

Graves’ disease(GD), named as toxic diffuse goiter, is an organ-specificautoimmune disease. It’s confirmed that, autoantibody combining with TSHR on thethyrocyte leads to the thyrocyte activation even hyperthyrea, although the concretemechanism is not clear. The researches have shown that the abnormal expression ofsome costimulatory molecules associates with the development of Graves’ disease.OX40and OX40L are important costimulatory molecules which belong to theTNFR and TNF superfamily. OX40/OX40L signal can promote the activation andproliferation of the T cells, inhibit the T cell apoptosis and regulate the invasion of Tcells in the inflammation sites. The studies indicated compared with the healthy controlgroup, the expression of OX40on T cells in Graves’ disease patients was significantlyupregulated, indicating that the OX40/OX40L signal may participate in the process ofGraves’ disease. However, the expression of OX40L in Graves’ disease is still unkonwn.Above all, this research mainly detected the abnormal expression of OX40/OX40Lin the peripheral blood of the Graves’ disease patients.PART Ⅰ: The abnormal expression of OX40/OX40L on lymphocyte subsetsin peripheral blood of primary Graves’ disease patients and its clinical significanceObjective: To detect the expression of OX40on CD4~+and CD8~+T cells andOX40L on the monocytes and B cells in the peripheral blood of primary Graves’ diseasepatients and healthy controls, then analyze the correlation between the expression ofOX40/OX40L and clinical parameters.Methods: The objects were the peripheral blood of150primary Graves’ diseasepatients,13thyroid adenoma and52healthy controls. The expression of theOX40/OX40L on the lymphocyte subsets of the peripheral blood was detected by FACS.According to the clinical reference value, the primary Graves’ disease patients were divided into high TRAb group and normal TRAb group, the difference between the twogroups was analyzed by statistical methods. Quantitative data were processed withstatistical software SPSS13.0.Charts and graph were drawn with GraphPad Prism5.0.The statistical significance between groups was assessed by T test. The level ofstatistical significance was established at p<0.05. The OX40/OX40L expression on thelymphocyte subsets of the Graves’ disease patients were further tested through confocalmicroscopy.Results:(1) Compared with the healthy control group and thyroid adenoma controlgroup, the expression of OX40on CD4+T cells and OX40L on monocytes and B cellsin Graves’ disease patients was significantly upregulated, while OX40expression onCD8+T cells had no significant change. Among above, OX40and OX40L expression ofhigh TRAb group were even higher.(2) Confocal microscopy approve the above results.Conclusion: OX40and OX40L were abnormally expressed on the lymphocytesubsets of the peripheral blood of Graves’ disease and their expressions were correlatedwith production of TRAb, suggesting that OX40/OX40L signal may participate in thedevelopment of Graves’ disease by promoting the prolonged activation of T and B cells.PART Ⅱ: The expression changes of OX40/OX40L on lymphocyte subsets inperipheral blood of primary Graves’ disease patients after therapy and theirassociation with the clinical statisticsObjective: To investigate the potential role of OX40/OX40L signal in diagnosisand treatment of the Graves’ disease, the expression of OX40and OX40L was detectedon lymphocyte subsets in the peripheral blood of primary Graves’ disease patientsbefore and after therapy and the correlation between the changes and clinical parameterswere analyzed.Method:28Graves’ disease patients were selected as objects, the expression ofOX40on CD4~+and CD8~+T cells and OX40L on the monocytes and B cells in theperipheral blood of these patients before and after therapy were detected by FACS. Theassociation between OX40/OX40L expression changes and the clinical statistics wereanalyzed through statistical methods.Result: After therapy, OX40expression on CD4~+T cell and OX40L expression onmonocytes and B cells return toward normal in the patients whose FT3or TRAb levels resume normal. OX40and OX40L expression maintained high levels in those whoseFT3or TRAb levels didn’t decline to normal.Conclusion: After therapy, OX40/OX40L expression declined with the drop ofFT3or TRAb level, indicating OX40/OX40L expression may contribute to determinethe prognosis of the disease. OX40/OX40L signal may also give a new thread forGraves’ disease therapy.