Expression Of CXCR3, CCR5and CCR3in Spleens Of Patients With Immune Thrombocytopenia

BACKGROUND and OBJECTIVE Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by a low peripheral blood platelet count. The pathogenesis of thrombocytopenia in ITP was proved to be complicated that not only impaired platelet production but also T cell-mediated immunity disorder participated in its complex mechanisms. The abnormal Th cell effect could direct autoreactive B cells to differentiate and secrete IgG autoantibodies, which resulted in platelet destruction in reticuloendothelial system. The spleen, served as the largest lymphoid organ, is the main site of autoreactive B cells activation, antiplatelet antibody production and platelet destruction. Splenectomy is an effective treatment in ITP patients with a success rate about66%. ITP is now considered a Thl disease, characterized by the oligoclonal accumulation of Th cells. Thl chemokine receptor CXCR3, CCR5and chemokine receptor CCR3have been reported in several autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Studies have shown a significant increase in expression of Thl chemokine receptors in Th-dominant diseases. The abnormal expression of chemokine receptors is Preliminary proved. However, the status of these chemokines and chemokines receptors in spleens of ITP patients is still unknown. In this study, we detected CXCR3, CCR5and CCR3protein and gene expression to analyze the expression of these chemokines receptors in spleens of ITP patients, and the significance in clinical application.METHODS The spleens of24ITP patients were studied, and18patients with traumatic splenic rupture were enrolled as normal controls. The histopathology of spleens was observed by hematoxylin-eosin staining (HE), and the positive rate of CXCR3, CCR5and CCR3in ITP group and control group was detected by immunohistochemistry SP method. CXCR3, CCR5and CCR3protein expression was analyzed by Western blot and mRNA levels were investigated by real-time polymerase chain reaction (RT-PCR).RESULTS The morphological characteristics of spleens in ITP patients were as follows:the reactive hyperplasia could be seen in follicles of the white pulp, the germinal central zone was enlarged and the marginal zone was thickened, the central arteries were thickened and fibrotic, and the density of the capillary vessel was increased. The dilatation and congestion of the splenic sinusoid, infiltration of neutrophilic leukocytes in the red pulp, and macrophage which phagocytized red cell and platelet accumulation in the splenic cord could be seen in ITP patients. ITP group displayed a higher rate of expression of Thl-associated chemokine receptors CXCR3and CCR5(90%vs.75%,100%vs.87.5%) but lower rate of expression of Th2-associated chemokine receptor CCR3(50%vs.62.5%) compared with the controls (P<0.05, respectively). Western blot analysis revealed that CXCR3, CCR5protein expression was significantly increased in ITP patients while CCR3was significantly reduced (P<0.05, respectively). Meanwhile, ITP patients displayed increased mRNA levels of CXCR3, CCR5but decreased gene expression of CCR3(P<0.05, respectively). All the differences were statistically significant (P<0.05, respectively).CONCLUSIONS Immune-inducted inflammation happened in spleens with ITP patients. The abnormal expression of Th1/Th2chemokine receptors may participate in splenic immune disorder in patients with ITP, which may indicate splenectomy is effective treatment for ITP, and using corresponding inhibitors may inhibit Thl-dominant expression and mitigate the progress of the disease.