| Background Thyroid-associated ophthalmopathy(TAO)is an organ specific disease characterized by autoimmune related inflammation disorders,which closely associated with Graves' disease(GD).Orbital tissues from TAO patients are found to be infiltrated with a large number of CD4~+,CD8~+T cells,which can secrete a variety of cytokines,chemokines and leukoregulins involved in pathological changes of orbital tissue.And programmed cell death factor 1(PD-1)is an important negative costimulatory molecular which can inhibit T cell activation and maintain immune tolerance,single nucleotide polymorphisms(SNPs)also prompts its associated with the susceptivity of GD,but its expression in TAO is rarely reported.The current first-line therapy for active,moderate-to-severe TAO is still glucocorticoids(GCs).Previous studies have established that GCs can increase PD-1 expression on CD4~+T cells and CD8~+T cells,and with a dose dependent,but PD-1 expression on CD4~+T cells and CD8~+T cells in peripheral blood of TAO patients before and after GCs treatment is not very clear.The aim of this study is to observe the percentages of CD4~+,CD8~+T cells and their PD-1 expression in peripheral blood mononuclear cells(PBMCs)from patients with TAO,and to explore the significance of the changes in pathogenesis and diagnosis of TAO.Besides,by observing percentages of CD4~+,CD8~+T cells and their PD-1 expression in PBMCs from active,moderate-to-severe TAO patients before and after glucocorticoids plus therapy,to explore effect of the therapy put on PD-1 expression and its clinical significance.Methods TAO patients,GD patients without ophthalmopathy and health controls were enrolled,The percentages of CD4~+,CD8~+T cells and their PD-1 expression in PBMCs were tested by flow cytometric method,the differences between three groups and their correlation with process of disease,laboratory datas and activity,severity of TAO were analyzed.Then collected active,moderate-to-severe TAO patients according to clinical active scores(CAS)and severity classification standards,all patients underwent 6 courses of glucocorticoids plus therapy,percentages of CD4~+,CD8~+T cells and their PD-1 expression in PBMCs were tested at beginning and 2 weeks after the last course of therapy,and analyzes its significance.Results(1)Percentages of CD4~+,CD8~+T cells in PBMCs of TAO patients were 36.2%±14.4%,20.7%±8.2% respectively,in GD patients were 32.0%±12.4%?19.1%±9.1% respectively,both of them were higher than that in health controls(17.4% ±7.4%,7.7% ± 4.8% respectively),the differences were statistically significantly(both P<0.01),there were no statistically significant differences between TAO and GD patients(both P>0.05).(2)PD-1 expression on CD4~+T cells of TAO patients were 11.0%±9.5%,in GD patients was 29.2%±26.7%,both of them were lower than that in health controls(52.2%±28.6%)(P<0.01,0.05 respectively),and TAO patients were lower than GD patients(P<0.05);PD-1 expression on CD8~+T cells of TAO patients was 18.1%±14.8%,in GD patients was 27.8%±23.1%,in health controls was 38.3%±24.2%,PD-1 expression on CD8~+T cells of TAO patients was lower than that in health controls,the difference was statistically significant(P<0.01),and there were no statistically significant difference between GD patients with TAO patients and health controls(P>0.05).(3)Partial correlation analysis showed that there were no significant correlation beween percentages of CD4~+,CD8~+T cells and their PD-1 expression in peripheral blood with process of oculopathy,FT3,FT4,TSH,TRAb,TPOAb,TGAb levels(P>0.05).(4)There were no significant differences of CD4~+,CD8~+T cells and their PD-1expression between active and inactive,mild and moderate-to-severe TAO patients(P>0.05).(5)Areas under the ROC curve of Percentages of CD4~+,CD8~+T cells in TAO peripheral blood were 0.743,0.744 respectively,the sensitivity in diagnosis of TAO were 81.8% and 87.9% respectively,specificity were 60.0%,60.0% respectively;Areas under the ROC curve of PD-1 expression on CD4~+,CD8~+T cells in TAO peripheral blood were 0.852,0.711 respectively,the sensitivity in diagnosis of TAO were 80.0% and 90.0% respectively,specificity were 83.0%,56.6% respectively.(6)Percentages of CD4~+T cells in TAO peripheral blood after glucocorticoids plus therapy was 26.7%±14.1%,which was lower than that before therapy(37.7% ± 12.1%),but was still higher than health controls(16.4%±7.0%)(both P<0.05);Percentages of CD8~+T cells in TAO peripheral blood after glucocorticoids plus therapy was 19.0%±12.0%,which had no significant difference with that before therapy(22.8% ± 9.2%)(P>0.05),and was still higher than health controls(6.2%±4.2%)(P<0.01).(7)PD-1 expression on CD4~+T cells in TAO peripheral blood after glucocorticoids plus therapy was 24.3%±12.0%,which was higher than that before therapy(14.3%±11.7%),but was still lower than health controls(55.5%±23.4%)(P<0.01);PD-1 expression on CD8~+T cells in TAO peripheral blood after glucocorticoids plus therapy was 32.6%±17.7%,which was higher than that before therapy(14.1%±14.5%),and had no significant difference with that in health controls(P>0.05).Conclusion(1)The aberrant percentages of CD4~+,CD8~+T cells and their PD-1 expression in TAO peripheral blood may participate in the autoimmune reaction process of TAO,the measurement has certain clinical application value.(2)After glucocorticoids plus therapy,PD-1 expression on CD4~+,CD8~+T cells were upregulated,which may be one of mechanism involved in glucocorticoids inhibiting autoimmune reaction of TAO. |
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