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ABSTRACT: Primary immune thrombocytopenia (ITP) is an acquired, organ-specific, autoimmune disease with many immune dysfunctions. Interleukin-27 (IL-27) can regulate T cell differentiation. However, it is unclear whether IL-27 correlates with the dysfunctions of T cell differentiation in ITP patients. Thus, to determine the roles of IL-27 in ITP, we studied the expression of IL-27/IL-27 receptor in ITP patients. The results indicated that the levels of IL-27 in the plasma of untreated active ITP patients were higher than in normal controls. We next evaluated the contribution of IL-27 to T cell differentiation. Our results indicated that IL-27 increased T-bet expression, inhibited GATA-3 and ROR-γt expression, and promoted the secretion of tumor necrosis factor-α, interferon-γ, and granzyme B of peripheral blood mononuclear cells from ITP patients. Also, we confirmed that IL-27 induced the differentiation of T helper (Th)-1 and Tc1 cells. In conclusion, IL-27 might play an important role in the pathogenesis of ITP by inducing the polarization of Th1/Tc1 cells and the production of proinflammatory cytokines.
Human immunology 12/2011; 73(3):240-7. · 2.55 Impact Factor
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ABSTRACT: To explore the role of CD72 in the pathogenesis of immune thrombocytopenia (ITP), we detected CD72, Sema4D, IL-2, IL-4, and IFN-γ mRNA expressions and the levels of plasma Sema4D, IL-2, IL-4, IL-6, and IFN-γ in ITP patients (n = 39) and controls (n = 23). The levels of plasma IL-2, IL-4, and IL-6 were assayed by radioimmunoassay, and the levels of plasma IFN-γ and Sema4D were analyzed by enzyme-linked immunosorbent assay. Sema4D, CD72, IL-2, IFN-γ, and IL-4mRNA expressions were analyzed by real-time quantitative reverse-transcription polymerase chain reaction. The expression of CD72 mRNA in ITP patients (n = 23) with active disease was significantly lower than that in patients in remission (p = 0.029) (n = 16) and controls (p = 0.0296) (n = 23). The IFN-γ/IL-4 mRNA (Th1/Th2) expression in ITP patients with active disease and in remission was significantly higher than that in controls (p = 0.0023, p = 0.0125, respectively). The expression of IL-2 mRNA in ITP patients with active disease was significantly lower than that in patients in remission (p = 0.0418) and controls (p = 0.004). The level of plasma IL-2 in ITP patients with active disease was significantly lower than that in patients in remission (p = 0.0029) and controls (p = 0.0101). The levels of plasma IL-4 in ITP patients with active disease and in remission were significantly higher than that of controls (p = 0.0093, p = 0.0053, respectively). CD72 mRNA expression level might correlate with Sema4D mRNA expression in peripheral blood mononuclear cells and level of plasma IL-2 in active ITP patients (p = 0.024 and p = 0.036). Our findings suggest that CD72 might be involved in the pathophysiological process of the ITP disease by increasing B-cell receptor signals.
Platelets 11/2011; · 1.85 Impact Factor
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ABSTRACT: To compare the efficacy of two different regimens of low doses rituximab for the treatment of adult patients with immune thrombocytopenia (ITP).
Fifty-one patients were enrolled in this study and was non-randomly assigned to receive 100 mg rituximab weekly for 4 weeks (group A, 31 cases) or a single dose of 375 mg/m2 rituximab (group B, 20 cases).
For group A: Overall and complete response (OR and CR) rates were 58% and 29% , respectively. In responders, the median time to response was 42 (10 -101) days, with a median follow-up time of 15 (10 - 16) months, 3 of 18 responders (17%) relapsed. For group B: OR and CR rates were 50% and 35% , respectively. In responders, the median time to response was 35 (18 - 108) days, with a median follow-up time of 13 (6 -17) months, 1 of 9 responders (11%) relapsed. No significant difference in the OR, CR, the relapse rate and relapse free survival was observed in patients between the two groups.
The low dose rituximab regimen (100 mg weekly for 4 weeks or a single close of 375 mg/m2) may be a useful alternative therapy in patients with ITP.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 09/2011; 32(9):583-6.
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ABSTRACT: To investigate the role of Th17 cells in immune thrombocytopenia (ITP) mice model.
ITP was induced by daily intraperitoneal injection of anti-platelet membrane CD41 antibody (MWReg30) into BALB/c mice, the mRNA expressions of Th17 cell associated transcription factors and cytokines in peripheral blood and spleen mononuclear cells were measured by real-time PCR, and the proportion of Th17 cells by FCM analysis.
The percentage of Th17 cell was significantly elevated in ITP mice both in splenocyte and peripheral blood as compared with that in normal controls (P<0.01). ITP mice had elevated mRNA expressions of IL-17F, IL-17A and IL-6 in splenocyte (P<0.05), and of IL-21 in peripheral blood (P<0.05). There was a positive correlation between IL-17A and IL-17F (r = 0.934, P = 0.000), and between IL-17A/IL-17F and IL-6 (r = 0.598, P = 0.001; r = 0. 619, P = 0.000).
Th17 cell might play an important role in the pathogenesis of ITP, at least involving in the clearance of platelets.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 09/2011; 32(9):592-6.
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Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 07/2011; 32(7):481-3.
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ABSTRACT: Genome-wide hypomethylation has been confirmed in patients with primary immune thrombocytopenia (ITP). Proteins containing methylcytosine-binding domain (MBD) are involved in promoter methylation as transcriptional repressors and promote the gene-silencing effect of DNA methylation. The purpose of this study was to investigate the methylation pattern of T cells and the relationship between genomic methylation and the expression of MBD2 and MBD4 in ITP patients. DNA deoxymethylcytosine content of CD4(+) cells from peripheral blood mononuclear cells was measured by enzyme-linked immunoassay. Real-time polymerase chain reaction was performed to quantify the transcription levels of MBD2 and MBD4 in peripheral blood mononuclear cells and CD4(+) cells. DNA dmC content in CD4(+) cells of ITP patients was significantly lower than in the controls (p = 0.001). The mRNA level of MBD2 and MBD4 in CD4(+) cells of ITP patients was statistically lower than those of the controls (p < 0.001). Positive correlations between methylation indexes and expression of each enzyme were observed in the control group (r(2) = 0.718, p = 0.004 for MBD2; r(2) = 0.608, p = 0.015 for MBD4). However, inverse correlations were found in ITP patients (r(2) = 0.604, p = 0.008 for MBD2; r(2) = 0.498, p = 0.027 for MBD4). Our results indicate that decreased expression of MBD2 and MBD4 might involve in the pathogenesis of ITP.
Human immunology 03/2011; 72(6):486-91. · 2.55 Impact Factor
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Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 03/2011; 32(3):201-3.
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Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 03/2011; 32(3):206-7.
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ABSTRACT: OBJECTIVE: To explore the immune tolerance induction (ITI) in a severe hemophilia A patient with inhibitor, and to improve the therapeutic efficacy for patient. METHODS: The FVIII:C was assayed by one-stage method and FVIII antibody by Bethesda method. Mutation screening of FVIII gene intron 22 inversion was performed using LD-PCR. RESULTS: FVIII gene intron 22 inversion was detected in this patient. Clinical tolerance to FVIII was successfully induced after administration of the ITI regimen combined with immunosuppression. A fall of inhibitor titer from 8 BU to 0 BU after treatment for 3 months, and in vivo FVIII recovery (> 66%) was normalized. The patient had no bleeding episode in the following 6 months. CONCLUSION: This is the first case report on successful immune tolerance induction therapy in Chinese hemophilia A patient. ITI is the most effective therapy for hemophilia A with inhibitor.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 09/2010; 31(9):577-580.
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ABSTRACT: Bmi-1 is a transcriptional repressor, which belongs to the polycomb group family. It has been demon- started that over-expression of Bmi-1 occurs in a variety of cancers, including several types of leukemia. Bmi-1 gene plays a key role in regulation of self-renewal in normal and leukemic stem cells. Acute myeloid leukemic cells lacking Bmi-1 undergo proliferation arrest and show signs of differentiation and apoptosis, which leads to the proposal of Bmi-1 as a potential target for therapeutic intervention in leukemia. The purpose of this study was to investigate the effect of short hairpin RNA (shRNA) targeting Bmi-1 on functions of K562 cell line. The shRNA eukaryotic expression vector targeting Bmi-1 was constructed and transfected into K562 cells through lipofectamine 2000. The mRNA and protein levels of Bmi-1 were detected by PCR and Western blot respectively. The proliferation of K562 after Bmi-1 silencing was measured by using MTT assay and clone formation assay. The cell cycle was detected by flow cytometry. The results indicated that among the four shRNA designed, there was a shRNA which efficiently interfered with the expression of Bmi-1. The results of PCR and Western blot validated that the Bmi-1 gene of K562 cells transfected with such a Bmi-1 shRNA was suppressed successfully. Although levels of Bmi-1 mRNA and protein were significantly reduced, delivery of this siRNAs had no effect on cell viability or growth. Flow cytometry analysis suggested that Bmi-1 inhibition did not affect the cell cycle. It is concluded that the suppression of Bmi-1 expression is not able to reduce proliferation of K562 cells, suggesting existence of some other parallel signaling pathways, which are fundamental for leukemic transformation and are independent of Bmi-1 over-expression. Bmi-1 over-expression may play a secondary role in chronic myeloid leukemia transformation.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 05/2009; 17(2):266-70.
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ABSTRACT: The family of T-cell immunoglobulin- and mucin-domain-containing molecules (TIMs) has an important role in immune regulation. TIM-3 is a transmembrane protein preferentially expressed on terminally differentiated Th1 cells and plays a role in T-helper (Th)-1-mediated autoimmune disease. Idiopathic thrombocytopenic purpura (ITP) is an acquired organ-specific autoimmune disease with a polarization of Th1. The purpose of this study was to investigate whether the -1516G>T, -574T>G, 4259G>T single-nucleotide polymorphisms within the TIM-3 gene contribute to the genetic susceptibility to ITP. Genotyping of TIM-3 -1516G>T, -574T>G, and 4259G>T was performed in 187 patients with ITP and 123 healthy individuals by polymerase chain reaction-restriction fragment length polymorphism assay. No significant differences existed in genotype and allele distributions between the patients with ITP and the controls in all three sites. There was strong linkage disequilibrium (LD; r(2) = 0.633) between -574T>G and 4259G>T, whereas -1516G>T was not in LD with -574T>G (r(2) = 0.007) or with 4259G>T (r(2) = 0.002). The -1516G>T, -574T>G, and 4259G>T of TIM-3 gene polymorphisms might not play an important role as a genetic risk factor in the pathophysiology of ITP.
Human immunology 04/2009; 70(6):398-402. · 2.55 Impact Factor
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Xiao-Li Chen,
Chun-Lan Dong,
Xiao-Ming Feng,
Zhen-Ping Chen, Ze-Ping Zhou,
Xian-Hui Xu,
Qin-Jun Zhao,
Zhi-Yong Qiu,
Qian Ren,
Lei Zhang,
Zhong-Chao Han
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ABSTRACT: The purpose of this study was to investigate the expression of human Factor IX (hFIX) in retrovirus-transfected human umbilical cord tissue derived mesenchymal stem cells (hUCT-MSCs). The pLEGFP-N1-hFIX vector was generated by cloning a 3.0 kb Bgl II-BamH I fragment from the pIRES2-EGFP-hFIX plasmid containing the hFIX cDNA and part of intron 1 of hFIX in pLEGFP-N1 vector. The retroviral supernatants were produced from the Phoenix packaging cell line and then infected the hUCT-MSCs. After selection with G418 for 10 day, the expression of FIX was detected by ELISA and Western blot. The biological activity of FIX was determined by the clotting assay employing human Factor IX-deficient plasma. The results showed that compared with the activity of pooled human normal plasma (100%), transduced cells produced biologically active hFIX with 100-130% activity in two-day culture supernatant and expressed hFIX at levels of 2.68 +/- 0.36 microg/10(6) cells/24 hours after G418 selection for 10 days. The secretion of hFIX into culture supernatant was also confirmed by Western blot analysis. It is concluded that genetically modified hUCT-MSCs can express biologically active hFIX and thus serve as an efficient drug delivery vehicle carrying hFIX used as a way of somatic gene therapy for hemophilia B.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 03/2009; 17(1):184-7.
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ABSTRACT: The study was aimed to investigate the potential immunotherapeutical values of umbilical cord tissue-derived mesenchymal stem cells (UC-MSC) on patients with chronic idiopathic thrombocytopenic purpura (ITP). UC-MSC was cocultured in vitro with splenocytes isolated from ITP patients who experienced splenectomy. The level of IgG antiplatelet antibody (PAIgG) was determined by a competitive micro-enzyme-linked immunosorbent assay (ELISA) method. The proliferation of platelet-reactive CD4+ T lymphocytes was also measured in the presence of UC-MSCs. The results showed that UC-MSCs could stimulate the spontaneous secretion of PAIgG in supernatants; In the platelet-inducing condition, UC-MSC inhibited the production of PAIgG at a low ratio of 1 UC-MSC to 100 splenocytes, but promoted at a high proportion of 1 UC-MSC to 10 splenocytes. Moreover, UC-MSC exerted a suppressive effect on proliferation of platelet-reactive T helper cells in a dose-dependent manner. It is concluded that the UC-MSCs can regulate secretion of antiplatelet antibodies in vitro. Its concrete regulation mechanism and potential immunotherapeutical value are need to further study.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 01/2009; 16(6):1372-5.
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ABSTRACT: OBJECTIVE: To report 7 cases of acquired hemoglobin H in myelodysplastic syndromes. CASE DATA AND DISCUSSION: Clinical materials of the 7 cases were retrospectively presented. Clinical features of the similar cases in literatures were reviewed. The criteria for diagnosis of this entity by Steensma and its pathogenesis were discussed. CONCLUSION: This entity is a new subtype of MDS with unique clinical features and pathogenesis, and might be a proper model in the study of MDS transformation.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 06/2007; 28(5):327-9.
