The Expression Of Costimulatory Molecule CD28,ICOS,PD-1 And CTLA-4 In RA Patients

Objective: To investigate the pathogenesis of CD28,ICOS,PD-1 and CTLA-4 in rheumatoid arthritis,we detected the expression of those costimulatory molecules on CD4+T cells in peripheral blood of RA patients by flow cytometry(FCM).In the meantime,we detected the expression of sCD86,s ICOS,sPD-1 and sCTLA-4 in plasma of RA patients by enzyme-linked immunosorbent assay(ELISA).Method:(1)We collected the peripheral blood of 63 RA patients(43 active patients and 20 stable patients)and 30 healthy controls,and detected the expression of CD28,ICOS,PD-1 and CTLA-4 on CD4+T cells in peripheral blood of active and stable RA patients and healthy controls by flow cytometry.(2)Detected the expression of sCD86,sICOS,sPD-1 and sCTLA-4 in plasma of 64 RA patients(39 active and 25 stable patients)and 20 healthy controls by ELISA.(3)And then analyzed the Spearman correlation between the expression of those costimulatory molecules and the DAS28 score.Result:(1)FCM analysis showed that,in RA patients,on CD4+T cells in peripheral blood of active group,the expression levels of CD28,ICOS and PD-1 were significantly higher than those of healthy controls group(P<0.01;P<0.05;P<0.01).There was no significant difference in the expression levels of CD28,ICOS and PD-1 between the active group and stable group(P>0.05;P>0.05;P>0.05).There was no significant difference in the expression levels of CTLA-4 between the active group and healthy control group and stable group on CD4+T cells in peripheral blood(P>0.05;P>0.05).(2)The results of ELISA showed that the expression levels of sCD86,sPD-1 and sCTLA-4 in plasma of active group were significantly higher than those in healthy control group(P<0.05;P<0.01;P<0.01).There was no significant difference in the expression of sICOS between active group and healthy control group(P>0.05).In active group,the expression levels of sPD-1 and sCTLA-4 were significantly higher than those in healthy group(P<0.01;P<0.01).However,there was no significant difference in the expression levels of sCD86 and sICOS between the active group and stable group(P>0.05;P>0.05).(3)The expression level of ICOS on CD4+T cells in peripheral blood of RA patients was positively correlated with the DAS28 score.The expression levels of CD28,PD-1 and CTLA-4 on CD4+T cells in peripheral blood of RA patients were not correlated with the DAS28 score.In plasma of RA patients,the expression levels of sPD-1?sCTLA-4 were positively correlated with DAS28 score,and the expression levels of sCD86 and sICOS were not correlated with DAS28 score.Conclusion: We proposed that the expression levels of CD28 and CD28 ligands CD86,ICOS,PD-1 and CTLA-4 were abnormal on CD4+T cells in peripheral blood and in plasma of RA patients.Therefore we proposed that those costimulatory molecules may play roles in the pathogenesis of RA.The expression levels of sPD-1 and sCTLA-4 in plasma of RA patients were positively correlated with DAS28 score,which suggesting that they were related to RA disease activity and may be activity monitoring indicators.