The Efffect Of All-trans Retinoic Acid On The Absolute Numbers Of CD4~+T Lymphocyte Subsets In Peripheral Blood Of Patients With Rheumatoid Arthritis

Purposes:1.To explore the association between CD4+T lymphocyte subsets and disease activity in patients with rheumatoid arthritis（RA）.2.To study the effect of retinoids on peripheral blood CD4+T lymphocyte subsets and evaluate the clinical efficacy in the treatment of RA,further revealing the therapeutic effect of retinoic acid in RA.Methods:80 patients with RA and 41 healthy vonlunteers were collected.All study subjects provided informed written consent,met the American College of Rheumatology RA revised classification criteria.(All patients met the 1987 classification criteria of RA of the American Rheumatology Association（ACR）.Those patients were excluded including severe infections,tumors,and other autoimmune diseases（AID）including SLE,SSc,and MCTD.The research content was divided into three parts:1.80 cases of RA patients and 41 cases of healthy vonlunteers were taken as case group and healthy control group respectively.The differences of CD4+T lymphocyte subsets（FACSCalibur Flow Cytometry,Becton Dickinson Bio,USA）in peripheral blood were compared between the two groups,and the association between CD4+T lymphocyte subsets and DAS28 score was analyzed.2.Based on the medication regimens collected,the RA cases were divided into three groups:（1）traditional treatment group（16 cases）:patients received only DMARDs treatment（including methotrexate,Flumetide,iguratimod,hydroxychloroquine）;（2） Retinoic acid treatment group（34 cases）:Patients received retinoids 10mg twice a week for the past year only;（3）Combination therapy group（30 cases）:Patients received retinoic acid 10 mg twice a weekand conventional DMARDs（including methotrexate,leflunomide,iguratimod,and hydroxychloroquine）in the past year.The changements of joint tenderness,joint swelling,VAS scores,ESR,and DAS28 scores before and after the three groups of medications were compared;and the differences in EULAR efficacy evaluation between the three groups were compared.3.Comparing CD4+T lymphocyte subsets in the peripheral blood of 34 patients with retinoic acid before and after administration;comparing the difference of CD4+T lymphocyte subsets in the peripheral blood of healthy individuals before and after treatment with retinoic acid;comparing the peripheral blood of healthy individuals after treatment with retinoic acid Differences in CD4+T lymphocyte subsets.Results:1.The levels of Th1%,Th1,Th1/Th2,and Th17/Treg of RA were significantly higher than that of healty volunteers（P<0.001）.The percentage and absolute nymbers of CD4⁺CD25⁺FOXP3⁺Treg were significantly lower compared with healthy control（P<0.001）.No significant difference was found between the two groups for Th2%,Th2, Th17%,and Th17 cell count（all P>0.05）.2.The DAS28 score of RA patients was positively correlated with Th17%and Th17/Treg levels（P≤0.001）,and negatively with the absolute numbers of CD4⁺CD25⁺FOXP3⁺Treg（P=0.001）.3.The numbers of joint swelling,tenderness,VAS score and DAS28 score in the traditional treatment group,retinoic acid group,and combination drug group were all significantly lower than that of before treatment（P<0.05）.No response in the traditional treatment group EULAR efficacy evaluation.The proportion（18.7%）was greater than the retinoic acid group（0%）and the combination group（0%）,and there was a statistically significant（P=0.009 and 0.014,respectively）.There was no significant difference in the number of joint pain,VAS score,ESR,DAS28 score between the three groups before treatment and after treatment（P>0.05）;EULAR efficacy of the three groups achieved good response to treatment and moderate reaction There was no statistical difference in the proportion（P>0.05）.4.The absolute numbers of CD4+CD25+FOXP3+Treg cells in the peripheral blood increased significantly after administration of retinoic acid compared with before treatment（P=0.01）,Th17%in peripheral blood decreased significantly（P<0.001）,Th17/Treg ratio significantly lower（P<0.001）;The percentage and absolute nymbers of of CD4⁺CD25⁺FOXP3⁺Treg in peripheral blood were significantly lower in the retinoid group before treatment than that in the healthy group（P all<0.001）and the ratio of Th17/Treg was significantly higher than that of the healthy group（P<0.001）;The ratio of Th17/Treg was significantly lower after treated with retinoic acid than that in the healthy control（P both<0.05）.There was no significant difference between the two groups for the absolute numbers of CD4⁺CD25⁺FOXP³⁺Treg（P>0.05）.Conclusion:1.The absolute numbers of CD4⁺CD25⁺FOXP³⁺Treg cells in peripheral blood of RA patients were significantly decreased.The decrease of Treg cells may be one of the main mechanisms of immune imbalance in RA.2.Retinoic acid can up-regulate the levels of CD4⁺CD25⁺FOXP³⁺Tregcells in peripheral blood of patients with rheumatoid arthritis and relieve disease activity to a certain extent,thus providing new ideas and new methods for the treatment of RA.