Expression And Clinic Significance Of PD-1/PD-L1 Costimulatory Molecules In Peripheral Blood Of Rheumatoid Arthritis

Background: Rheumatoid arthritis(RA) is an autoimmune disease characterized by synovitis of joints, progressive destructive of cartilage and bone. Its disability rate is high and its exact pathogenesis remains unknown. Recent researches have indicated that a number of receptor-ligand molecules of costimulators take part in the pathologic processes of many antoimmune diseases in different ways and stages of the immune responses. Programmed death 1 belongs to CD28 superfamily, while programmed death ligands 1(PD-L1) is a new discovery in B7 family. As a negative costimulatory molecule,it plays a role in many autoimmune diseases. So, it could provide new therapeutic targets against RA by studying the expression features , analyzing the relevances between PD-1/PD-L1 expression level and activity indexes of RA and the biological significance of PD-1/PD-L1 molecules in RA.Objective: To explore the expressions and the significance of costimulatory negative molecules PD-1/PD-L1 in peripheral blood of rheumatoid arthritis.Methods: The fresh peripheral blood was collected from 56 RA patients and 20 healthy people.In RA patients 29 cases were active, else were inactive. The core indicators of RA activity were evaluated: the patients' pain score, morning stiffness, tender joint and swollen joint counts, health Assessment questionnaire scores(HAQ), rheumatoid factor (RF) ,anti-CCP antibody,erythrocyte sedimentation rate (ESR), C-reactive protein (CRP). PBMC were isolated, then FCM were proceeded to determine the expressions of CD4~+PD-1~+,CD8~+PD-1~+,CD14~+PD-L1~+,CD19~+PD-L1~+, and analyze the relevances between PD-1/PD-L1 and activity indexes of RA.Results:(1) The expression of PD-1 on PBMC in RA group was remarkably higher than the control group (16.74±6.67% VS 13.25±2.71%, P<0.05). (2) In RA group and control group,the expression of CD4~+PD-1~+ on PBMC were(9.80±5.28)% and (5.94±1.41)% respectively;the expression of CD14~+PD-L1~+ were(32.63±16.08)% and(21.99±6.68)% respectively.The differences of the expression of CD4~+PD-1~+ and CD14~+PD-L1~+ between them were significant (P <0.05). (3) The expression of PD-1/PD-L1 between active RA patients and inactive patients have no difference. (4) The expression of PD-1 on PBMC were correlated with RF and anti-CCP (P <0.05) ,but had no correlations with age, disease duration, the patients' pain score, morning stiffness, tender joint and swollen joint counts, HAQ, ESR and CRP (P>0.05). (5) The expression of PD-L1 on PBMC had no correlation with age,disease duration ,the patients' pain score, morning stiffness, tender joint and swollen joint counts, HAQ, ESR,CRP,RF and anti-CCP antibody (P>0.05).Conclusions:The abnormal high expression of costimulatory negative molecules PD-1/PD-L1 on CD4~+ T lymphocyte cells and CD14~+mononuclear cells in RA patients demonstrated that PD-1/PD-L1 may be involved in the process of RA. PD-1 signal was mainly expressed on CD4~+ T lymphocyte cells, and PD-L1 signal was laregely expressed on CD14~+ mononuclear cells. Moreover, the expression level of PD-1 on T lymphocyte cells had positive correlations with RF and anti-CCP antibody, but with no correlation with some disease activity index such as ESR and CRP. These indicated that and PD-1 signal path may run through from the beginning to the end in RA and PD-1can possibly be used as a immunologic mark for RA.