Study On The Expression Of Negatively Regulate Molecules PD-1 And CTLA-4 In Primary Immune Thrombocytopenia

Objective:primary immune thrombocytopenia (ITP) is one kind of thrombocytopenia caused by abnormal immune disorder which speed up the destruction and block forming platelet. Activated auto-reactive T-cell is the key of cell immune disorder of ITP. If the expression of negatively regulate molecules which is deficient or low will destruct immune tolerance and finally occur autoimmune diseases.It’s unclear whether negatively regulate molecules PD-1 and CTLA-4 play an important role in ITP which need to verify. Consequently, the research emphasize testing the expression of PD-1 and CTLA-4 and the expression of cytokines associated with them among ITP patients,to explore the correlation between ITP and these molecules,thus search the new target of treating with ITP.Method:Collected 20 cases of newly diagnosed ITP patients and 20 cases of healthy controls during May 2014 to November 2014 in the hematology department of Lanzhou University Second Hospital, all patients treated with standard oral prednisone. Acquired peripheral blood before treatment and after the 4 week’s treatment course, detected the change of peripheral venous blood platelet count in ITP patients, Using the flow cytometry to detect the percentage of CTLA-4 and PD-1 on CD4+T cells and CD8+T cells applying the ELISA to detect the expression of cytokines associated with PD-1 and CTLA-4.Results:The percentage of CD4+PD-1+ and CD8+PD-1+ peripheral blood lymphocytes in ITP patients decrease before treatment than the HD group, the difference is significant. The proportion of CD4+PD-1+and CD8+PD-l+lymphocytes is higher after treatment than that before treatment, there is a significant difference. The percentage of CD4+CTLA-4+T lymphocytes (1.35±0.48%) and CD8+CTLA-4+T lymphocytes(0.68±0.32%) in ITP patients after treatment is higher compared with the previous treatment and the HD group increases, the difference is statistically significant (P<0.01). The expression of IL-2 in ITP group after treatment with Glucocorticoid significantly reduced compared with before treatment, the expression of PD-1 is negatively correlated with IL-2.In the aspect of TGFβ1 expression, It significantly increased after treatment in ITP group than before treatment and the expression of CTLA-4 is positively correlated with the change of it.Conclusion:The pathogenesis of ITP may be coordinated with CTLA-4,PD-1 of negatively regulate molecules and the cytokines IL-2 and TGFβ1 related with them. The expression of CTLA-4 and TGFβ1 is positively correlated, the expression of PD-1 and IL-2 is negatively correlated.Glucocorticoid can increase the expression of negatively regulate molecules CTLA-4 and PD-1, promoting the secretion of TGFβ1 and decreasing the secretion of IL-2 respectively, which play a role in inhibition of immune response.To a certain extent, Glucocorticoid can improve immune disorders of patients with ITP.