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A Study On The Effect Of CD47, TSP-1 And Cytokines In Children With Idiopathic Thrombocytopenic Purpura

Posted on:2010-01-12Degree:MasterType:Thesis
Country:ChinaCandidate:Z J ZhangFull Text:PDF
GTID:2144360278972555Subject:Academy of Pediatrics
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Objective:Idiopathic thrombocytopenic purpura is a common hemorrhagic diseases of children caused by increased peripheral platelet destruction. Currently we have certain understanding about the immune mechanism of ITP, but there are still a lot of links which lack of unity of understanding. Specific pathogenesis of ITP has not yet been fully clarified. CD47 (integrin-associated protein) is a ubiquitously expressed 50kD transmem-brane glycoprotein that is found on all kinds of cells. In 2005, Olsson found that platelet CD47 and macrophage SIRPα(inhibitory receptor signal regulator proteinα) play an important role in regulating normal platelet homeostasis and autoimmune elimination of opsonized platelets in experimental mice ITP, which suggests a gene-dose effect of CD47 in this system. Up to now,we know that TSP-1 inhibits the growth of bone marrow megacaryocyte. The binding of TSP-1 and CD47 is related to platelet aggregation. Meanwhile, it selectively downregulates the production of human IL-12.IL-4 and IL-12 are key factors which maintain the balance of Th1/Th2. CD47 expression was tested in 10 ITP children by quantitative flow cytometry on platelets and in plasma.The levels of serum TSP-1, IL-4,IL-12 were also tested in ITP group, so as to find the connection between CD47, TSP-1 and ITP, discover the change and significance of Th1/Th2 in the outbreak of ITP, expand our understanding of the cause and the process of ITP, and provide some theoretical help for doctors to treat,estimate ITP and predict an adverse prognosis.Methods: According to the ITP standard, 10 acute ITP children (7 boys and 3 girls from 1. 5 to 12 years old) were included in our research group. Their thrombocyte number was (10~30)×10~9/L. They all had ITP for the first time and had been ill for 1 to 7 days. 10 healthy donors (6 boys and 4 girls from 3 to 10 years old) were as control. The leves of TSP-1, IL-14 and IL-12 in serum were measured by using ELISA.Flow cytometry was used to analyse CD47 on platelets and in the plasma.They were detected before and after treatment respectively. Methods of treatment were as follow:①The patients were injected human immunoglobulin intravenously for 5 days. The dose was 0.4g/(kg.d) ;②At the same time the patients were injected dexamethasone 0.2~0.4 mg/(kg.d) for 3~5days and then, dexamethasone was substitued by taking prednisone orally. The dose of prednisone decreased gradually. Blood samples were collected when the number of thrombocyte increased to 100×10~9/L.Results: 1.CD47 expression on platelets was predominantly identical in the normal group (1937±64) U and ITP children (1947±40) U, with no significant difference observed ( P=0.071, t=0.139) .2. CD47 detected in the plasma of the normal group was (3419±371) U. Significantly higher levels of CD47 [(4021±398) U] was observed in the plasma of ITP children (P=0.003, t=3.496) ; After treatment,CD47 observed in the plasma of ITP children was (3743±420)U, which was obviously lower than ITP children before treatment (P<0.001, t=21.614). CD47 detected in the plasma of the normal group was no significant difference compared with ITP children after treatment (P=1.831, t=0.084). 3. The serum TSP-1 content of the ITP children was (185.41±24.91) ng/ml, which was obviously higher than the normal group[( 154.71±37.71) ng/ml] ( P=0.046, t=2.148). After treatment the serum TSP-1 content of the ITP children was (168.15±26.33) ng/ml, which was obviously lower than ITP children before treatment ( P<0.001, t=8.468) .The serum TSP-1 content of the normal group was no significant difference compared with ITP children after treatment (P=0.368, t=0.924) .4. The serum IL-4 content of the ITP children was (47.12±6.31) pg/ml, which was obviously lower than the normal group[(55.12±6.35) pg/ml] ( P=0.011, t=2.825) . After treatment the serum IL-4 content of the ITP children was (48.13±6.18) pg/ml , which was obviously higher than ITP children before treatment (P<0.001, t=6.245). The serum IL-4 content of the normal group was obviously higher than ITP children after treatment (P=0.023, t=2.494).5. The serum IL-12 content of the ITP children was (74.97±2.28 ) pg/ml, which was obviously higher than the normal group[ (70.70±3.02) pg/ml] ( P=0.002, t=3.566) . After treatment the serum IL-12 content of the ITP children was (73.40±2.03) pg/ml, which was obviously lower than ITP children before treatment ( P=0.010, t=3.244) .The serum IL-12 content of the normal group was obviously lower than ITP children after treatment (P=0.031, t=2.347).Conclusions: 1. CD47,TSP-1 are related to the cause of ITP.2. Th1/Th2 in the ITP children is abnormal. The strengthened activity of Th1 and its being in a dominate state put the cells of Th2 in a depressed state.3. After injected human immunoglobulin and dexamethasone intravenously, the number of thrombocyte increases and becomes normal. The immune function of ITP patient restored partially. The patient's immune function is still in disorder and it is necessary to continue to use immune remedy.4. In clinic, the level of IL-12 and IL-4 can be used to estimate ITP and predict an adverse prognosis.
Keywords/Search Tags:CD47, TSP-1, IL-4, IL-12, thrombocytopenia, purpura
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