The Expression Of Costimulatory Molecule ICOS/ICOSL In The Peripheral Blood Of RA Patients And Its Clinical Significance

Rheumatoid arthritis (RA) is a chronic autoimmune arthritis characterized byprogressive joint destruction. The main clinical manifestations of RA is chronic,symmetry, multi-synovial arthritis and extra-articular lesions. Joint becomed deformityand stiffness gradually involving the damage of articular cartilage and bone, whichwould induced joint function loss.Its exact pathogenesis is so complicated that itremains unknown.ICOS/ICOSL are important costimulatory molecules which belong to the B7/CD28superfamily. ICOS expression was increased on activated T cells,the reaction ofICOS/ICOSL could promote the T cells’activation and proliferation, play an importantrole in immune response. More and then, ICOS/ICOSL signal was necessary to thematuration of B cells. For lacking the ICOS/ICOSL signal, T cells dependent B cellsresponse were severely destroyed.Now widely recognized that during incidence and development process of RA, alarge number of autoantibodies produced due to over activation of T and B cells, whichlead to chronic inflammation in multiple body parts.ICOS/ICOSL which could induceand activate T cells might involve in the immune disorder of RA.Above all, thisresearch mainly detected the ICOS/ICOSL molecules expression in peripheral blood ofRA patients, then to expore the function and mechanisms of ICOS/ICOSL signal inRA.Objective:To investigate the level of lymphocyte subsets in the peripheral blood ofRA patients and to detect the expression of ICOS on CD4+T cells and ICOSL on themonocytes and CD19+B cells in the peripheral blood. And then to investigate thecorrelation between the change expression of ICOS and ICOSL on lymphocyte subsetsin the peripheral blood of primary RA disease patients and the clinicalparameters.Furthermore, to investigate the potential role of ICOS/ICOSL signal in diagnosis and treatment of the RA disease.Methods:The objects were the peripheral blood of85primary RA disease patients,30osteoarthritis and50healthy controls. Flow cytometry method were used to detectthe abnormal expression of lymphocyte subsets and the the expression of ICOS/ICOSLon peripheral T lymphocyte,monocyte and B lymphocyte in periphera1blood andsynovial fluid.By the real-time PCR and immunohistochemistry, ICOS/ICOSLexpression pattern was detected in PBMCs. According to the clinical reference value,the primary RA disease patients were divided into active group and inactive group, thedifference between the two groups was analyzed by statistical methods.15RA diseasepatients were selected as objects. The number of lymphocyte subsets, the expression ofICOS on CD4+and ICOSL on the monocytes and B cells in the peripheral blood ofthese patients before and after therapy were detected by FACS. The association betweenICOS/ICOSL expression changes and the clinical statistics were analyzed throughstatistical methods. Quantitative data were processed with statistical software SPSS13.0.The statistical significance between groups was assessed by T test. The level ofstatistical significance was established at p<0.05. Charts and graph were drawn withGraphPad Prism5.0.Results:(1)Immunohistochemical results showed that both ICOS and ICOSLexpression on infiltrated lymphocytes.(2) Compared with the osteoarthritis controlgroup, the percentage of ICOS on CD4+T lymphocytes and ICOSL on CD14+monocytein synovial fluid was significantly upregulated in RA Patients.(3)Further real-time PCRstudy showed that expression of both ICOS and ICOSL mRNA of PBMCs in RA wasremarkedly higher than in control.(4) Compared with the healthy control group, thepercentage of CD4+T lymphocytes was significantly upregulated in RA Patients, thepercentage of CD19+B lymphocytes and the percentage of CD4+CD28-T cells washigher than control while the percentage of CD14+monocyte had no significant change;Compared with the healthy control group and osteoarthritis control group, theexpression of ICOS on CD4+T cell in RA disease patients was notably upregulated,ICOSL on CD14+monocyte and CD19+B lymphocytes in peripheral blood of RApatients was increased markedly.(5)According to the clinical reference value, theprimary RA disease patients were divided into active group and inactive group, thepercentage of CD19+B lymphocytes in active group PBMCs was even higher thaninactive group, ICOSL on CD14+monocyte and CD19+B lymphocytes in peripheral blood of active group was increased markedly; ICOS expression on CD4+T cell andICOSL expression on monocytes and B cells for the possive RF patients were all higherthan the negative RF patient,but they were not corrected with RF, the expression ofICOS/ICOSL had no correlation with other clinical features of RA patients; For thesame patient, the percentage of CD4+CD28-T cells was lower than before therapy,ICOS expression on CD4+T cell and ICOSL expression on monocytes and B cells weredecreased after therapy.Conclusion: The level of lymphocyte subsets was changed in peripheral blood ofRA. The expression of ICOS/ICOSL was abnormally increased on the lymphocytesubsets of the peripheral blood of RA disease. The abnormally expression ofICOS/ICOSL was different between active group and inactive group. Suggesting thatICOS/ICOSL signal may participate in the development of RA disease by promoting theprolonged activation of T and B cells. It will have potential value in clinical medicine.After therapy, ICOS/ICOSL expression declined, indicating ICOS/ICOSL expressionmay contribute to determine the prognosis of the disease.The expression ofICOS/ICOSL had no correlation with clinical parameters. These indicated that andICOS/ICOSL signal path may run through from the beginning to the end in RA,but itcouldn’t be used as a immunologic mark for RA.