Studies On Cd₄⁺cd₂₅+foxp3⁺regulatory T Cells In Patients With Graves' Disease And Patients With Rheumatoid Arthritis

Background and ObjectiveCD₄⁺CD₂₅⁺ regulatory T cell was firstly reported by Sakaguchi in 1995. Many evidences have showed Treg was highly relative to systematic and organ-specific autoimmune diseases.Graves'disease is one of the autoimmune diseases in thyroid gland. Pathogenesis of Graves'disease is unclear, and possibly there is a relation between Treg gene defections and auto-antibody. Rheumatoid Arthritis(RA) is a systematic autoimmune disease mainly resulted from abnormal immune response of T cell.This study was to evaluate the percentage of CD₄⁺CD₂₅⁺FOXP3⁺ Treg in patients with Graves'disease and RA patients, and analyze the roles of CD₄⁺CD₂₅⁺FOXP3⁺ Treg in Graves'disease and RA.MethodsThe subjects included patients with Graves'disease and patients with RA. Fifty-two cases of Graves'patients and thirty-three healthy donors with the similar proportion in age and gender were selected. The percentage of CD₄⁺CD₂₅⁺FOXP3⁺ Treg was analyzed by flow cytometry (FCM) and the content of serum TRAb was measured by RIA in peripheral blood of the Graves'disease patients at the stage of preliminary diagnosis, drug subtract and drug withdrawal. Then, a comparison and the correlation in the quantitation of CD₄⁺CD₂₅⁺FOXP3⁺ Treg and TRAb described above was analyzed. After treatment with antithyroidism drugs, the percentage of CD₄⁺CD₂₅⁺FOXP3⁺ Treg in reocurrence patients in one year and non-reocurrence patients were analyzed retrospectively. As for RA patients,36 patients without using sterol and immunodepressant were selected, while 30 osteoarthritis(OA) patients and 33 healthy donors served as control groups. The percentage of CD₄⁺CD₂₅⁺FOXP3⁺ Treg in peripheral blood and synovial fluid were tested by flow cytometry.ResultsThe percentage of CD₄⁺CD₂₅⁺FOXP3⁺Treg in peripheral blood of Graves'disease patients was (4.00±0.42)%, which was significant lower than it was in healthy donors (P<0.01). The content of TRAb in serum of Graves'disease patients was (32.50±17.78)U/L, which was significant higher than it was in control group (P<0.01). There was a negative correlation between the quantitation of CD₄⁺CD₂₅⁺FOXP3⁺ Treg and TRAb in Graves'disease patients at the stage of preliminary diagnosis (r=-0.696, P<0.01). No correlation was showed between CD₄⁺CD₂₅⁺FOXP3⁺ Treg and TRAb at the stage of drug subtract and discontinuation (r1=0.05, r2=-0.03, P>0.05).At preliminary stage, the percentage of CD₄⁺CD₂₅⁺FOXP3⁺Treg in recurrence patients with Graves'disease was (4.11±0.37) %, which was no different from non-recurrence patients ( P>0.05). Compare to result at preliminary diagnosis stage (4.11±0.37) %, the percentage of CD₄⁺CD₂₅⁺FOXP3⁺ Treg were increased (0.97±0.57) %, which was significantly lower than it was in non-recurrence patients (P<0.01). The percentage of CD₄⁺CD₂₅⁺FOXP3⁺ Treg in peripheral blood of RA patients was (5.97±1.17) %, which was significantly lower than it was in OA patients and control group (P <0.05). However, no difference was found between OA patients and control group (P >0.05).The percentage of CD₄⁺CD₂₅⁺FOXP3⁺ Treg in synovial fluid of RA patients was (14.93±2.83) %, which was significant higher than it was in OA patients (P <0.01). The percentage of CD₄⁺CD₂₅⁺FOXP3⁺ Treg in synovial fluid of RA and OA patients were higher than they were in peripheral blood (P <0.01).ConclusionsThe percentage of CD₄⁺CD₂₅⁺FOXP3⁺ Treg decreased in peripheral blood of Graves'disease patients, illustrating a negative immune control of Treg, which resulted in autoantibody. Drug could be withdrawn when TRAb turned to negative. However, disease might reoccur if the percentage of CD₄⁺CD₂₅⁺ FOXP3⁺ Treg was not recovery.The percentage of CD₄⁺CD₂₅⁺FOXP3⁺ Treg decreased in peripheral blood of RA patients, which illustrated a negative immune control of Treg, a indispensible factor for pathology. In synovial fluid of RA patients, the percentage of CD₄⁺CD₂₅⁺FOXP3⁺ Treg was significant higher than it was peripheral blood and synovial fluid of OA patients.The finding demonstrated that the increased percentage of CD₄⁺CD₂₅⁺FOXP3⁺ Treg might be just a secondary reaction after inflammation appeared in synovial fluid. The percentage of CD₄⁺CD₂₅⁺FOXP3⁺ Treg in peripheral blood decreased at preliminary or active stage in many autoimmune cases. But different results happened after drug intervention or in a part of the body(such as synovial fluid ).