Percentages of PD-1+CD4+T cells and PD-L1+DCs are increased and sPD-1 level is elevated in patients with immune thrombocytopenia.

The present study is to measure the expression of programmed death (PD)-1 / programmed death ligand-1 (PD-L1) negative costimulatory molecules, soluble format sPD-1 in patients with immune thrombocytopenia (ITP), and to investigate their correlation with the secretion of cytokines. A total of 35 patients with ITP were included in the present study. Twenty healthy subjects who received physical examination at our hospital were included as control group. Peripheral blood was collected from all ITP patients and healthy subjects. Flow cytometry was performed to determine the percentages of PD-1+CD4+T cells and PD-L1+DCs in ITP patients and healthy subjects. Enzyme-linked immunosorbent assay was performed to measure the concentrations of interferon (IFN)-γ, interleukin (IL)-17 and sPD-1 in peripheral blood from ITP patients and healthy subjects. Percentages of PD-1+CD4+T cells and PD-L1+DCs in peripheral blood from ITP patients before treatment were significantly higher than that from healthy subjects, but were not different from those after treatment. Serum concentrations of IFN-γ, IL-17 and sPD-1 in ITP patients before treatment were significantly higher than those in healthy subjects, and these concentrations were significantly reduced after treatment. The concentration of sPD-1 was positively correlated with the concentration of IFN-γ, and negatively correlated with platelet count. Percentages of PD-1+CD4+T cells and PD-L1+DCs in ITP patients are higher than those in healthy subjects, but elevated sPD-1 concentration in the blood blocks PD-1/PD-L1 signaling pathway, leading to unaffected Th cell function. Elevated concentrations of IFN-γ and IL-17 in the blood may participate in the occurrence and development of ITP.

The effect of single course high dose dexamethasone on CD28/CTLA-4 balance in the treatment of patients with newly diagnosed primary immune thrombocytopenia.

To evaluate the effect of a single course of high dose dexamethasone (HD-DXM) on CD28 and CTLA-4 expression in patients with newly-diagnosed primary immune thrombocytopenia (ITP). Twenty-8 ITP patients (18 females and 10 males, age range 18-65 years, median age 38.5 years) enrolled in this study and 26 healthy volunteers (19 women and 7 men, age range 16-66 years, median age 37 years) served as a control group. The patients were treated with HD-DXM (40 mg/day) for 4 consecutive days. CD28 and CTLA-4 expression was assessed by flow cytometry once-monthly for 6 months. Plasma levels of the cytokines IFN-γ and IL-10 were determined by enzyme-linked immunosorbent assay. One month after treatment, a platelet response was observed in 23 (82%) of the patients. The response rates over the next 5 months were 71%, 57%, 53%, 46%, and 39%, chronologically. We observed a significant decrease in CD28 expression after the first month (34.7 ± 4.8% vs. 44.5 ± 4.4% before treatment), after which the CD28 levels gradually increased. In contrast, CTLA-4 expression increased after the first month (3.2 ± 0.5% vs. 0.8 ± 0.4 before treatment), after which the CTLA-4 levels gradually decreased. Similar dynamic changes were seen in the levels of IFN-γ and IL-10. The dynamic changes of CD28 and CTLA-4 were consistent with those of IFN-γ and IL-10 and with the effectiveness of HD-DXM in the treatment of ITP. Our results suggest that a disturbed CD28/CTLA-4 balance may contribute to the immunopathogenesis of ITP.

Polymorphic variation of inflammation-related genes and risk of non-Hodgkin lymphoma for Uygur and Han Chinese in Xinjiang.

Polymorphisms of inflammation-related genes have been found to be associated with non-Hodgkin lymphoma (NHL) or some of its subtypes, but only a few relevant data have been reported in China. In this study, the Snapshot method was used to assess genetic variation; a total of 14 single nucleotide polymorphisms (SNPs) for 6 inflammatory factors in 157 NHL cases (64 Uygur ethnic subjects, 93 Han Chinese) and 435 controls (231 Uygur and 204 Han Chinese) were studied from the Xinjiang province of China. Haplotype distribution was estimated using PHASE 2.3 software. Statistical differences in the genotype and haplotype frequencies between case and control groups were also considered and estimated. For the Han population, the geneotype distributions for TNF- αrs1800629, TNF-αrs1800630, IL-6 rs1800795, IL-6 rs1800797, NF-KB1 rs1585215 and TLR-4 rs4986790 showed significant differences between the case and control groups (p<0.05). The TNF-α gene frequencies of ACG and CCA haplotypes in the cases were higher than in the controls (OR=2.45, 95% CI: 1.55-3.89, p=0.0002, OR=2.53, 95% CI: 1.10-5.80, p=0.029, respectively), and the same findings were detected for TNF-ß gene CA haplotype (OR=1.87, 95% CI: 1.21-2.90, p=0.0054). However, for the Uygur population, no such significant differences were detected within the gene-type distribution of the 14 SNPs. The TNF-α gene frequency of the CCA haplotype between the two groups (OR=1.98, 95% CI: 1.11-3.51, p=0.021) revealed a statistically significant difference. Our results showed that polymorphic variations of inflammation-related genes could be important to the NHL etiology of the Han population, and that these may only have limited influence on the Uygur population.

[Application of karyotypic analysis in myelodysplastic syndrome].

OBJECTIVE: To explore the applications of karyotypic analysis in the diagnosis and prognosis of myelodysplastic syndrome (MDS). METHODS: Chromosomal analysis was performed with short-term cell cultures and R-banding techniques in 129 MDS patients. And the technique of FISH was employed for clinical follow-ups in 28 MDS patients. Based on the result of abnormal karyotype, the patients were divided into three groups: low risk group , intermediate risk and high risk group. The leukemia transformation time and survival time between these three groups were compare. RESULTS: Among them, 52 patients (40.3%) had numeral karyotypic abnormalities of chromosomes and structural alterations. Complex abnormal karyotype was the most common and accounted for 30.8% (16 cases). The frequencies of 20q(-) and +8 were 19.2% (10 cases) and 15.4% (8 cases)respectively. Six cases were positive by FISH, however, of whom, were negative for conventional cytogenetics. The follow-up data were available in 88 patients with a median follow up duration of 11(3, 60) months, 27 cases (30.7%) progressed to acute leukemia. The rate of leukemia transformation were 27.8% (15/54), 23.5% (4/17) and 47.1% (8/17) in the low, intermediate and high risk groups respectively. The median durations of leukemic transformation were > 60 (14, > 60), 48 (35, > 60) and 7 (6, 12) months in the low, intermediate and high-risk groups and the median survival times were 26(15, > 60), 21(14, 35) and 10(6, 13) months respectively. The median durations of leukemic transformation and median survival periods in the high-risk groups were shorter than those in the low and intermediate risk groups (all P < 0.05). CONCLUSION: Karyotypic analysis has important values in the diagnosis and prognosis of MDS.

[Expression of CD4+ CD25+ regulatory T cells and TGF-ß1 in patient with idiopathic thrombocytopenic purpura].

AIM: To investigate the expression rate of CD4+ CD25+ regulatory T cells and TGF-ß1 in peripheral blood of the patients with idiopathic thrombocytopenic purpura (ITP), and the role they play in the pathogenesis of ITP. METHOD: The population of CD4+ CD25+ regulatory T cells in peripheral blood of 31 patients and 25 healthy donors was evaluated by flow cytometry, ELISA was used to test the level of TGF-ß1 in blood serum, and analysed the correlation between levels of CD4+ CD25+ regulatory T cells and TGF-ß1. RESULTS: ITP patients had a lower proportion of CD4+ CD25+ regulatory T cells than the healthy donors (P<0.05). The level of TGF-ß1 in ITP patients was also lower than healthy donors (P<0.05). There was not positive correlation between levels of CD4+ CD25+ regulatory T cells and TGF-ß1 (P<0.05). CONCLUSION: The results indicate that the decreasing of CD4+ CD25+ regulatory T cells in ITP patients may be connected with cellular immunity disturbance of idiopathic thrombocytopenic purpura. Further research need to be performed in metabolic changes on CD4+ CD25+ regulatory T cells and TGF-ß1 in patients with idiopathic thrombocytopenic purpura.

[Retinoic acid in treating acute promyelocytic leukemia with hyperleukocytosis and its therapeutic strategy].

In order to investigate the occurrence of hyperleukocytosis in treating acute promyelocytic leukemia (APL) patients with all trans retinoic acid (ATRA) and to explore the influence of the level of leucocyte on curative effect of ATRA, the APL patients were divided into three different groups according to the count of leucocyte in peripheral blood. Patients with WBC count less than 30x10(9)/L were administered with ATRA alone (the first group), patients with WBC count more than 30x10(9)/L were administered with ATRA alone (the second group) and patients with WBC count more than 30x10(9)/L were treated with ATRA+cytotoxic drugs (the third group). The results showed that hyperleukocytosis were found in 23 out of 39 patients (58.97%). Total remission rates in the second group and in the third group were 91.3%. The remission rates in the first, second and third groups were 100%, 87.5% and 90.9%, respectively. It is concluded that the ATRA in combination with cytotoxic drugs can efficiently control the occurrence of hyperleukocytosis during ATRA-treating APL and reduce the early mortality.

[Early prediction of efficaciousness after first course of chemotherapy in de novo acute leukemia].

To achieve the complete remission (CR), acute leukemia (AL) patient must get through the period of myeloid ablation after chemotherapy that the white blood cell (WBC) count in peripheral blood decreases rapidly. To observe the relationship of WBC count with therapeutic effectiveness after chemotherapy in previously untreated AL, eighty cases of previously untreated acute leukemia who took the first induction chemotherapy course were analyzed. Blood routine was carried out 2 to 3 times every week while the bone marrow pictures on 12th and 20th day after chemotherapy were observed. 80 patients were divided into 3 groups based on the lowest value of WBC count after chemotherapy: 0.9 x 10(9)/L group. The results showed that the complete remission rates after the first course of chemotherapy were 60 vs 55.6 vs 27.3% respectively in the three groups which WBC counts were 0.9 x 10(9)/L. The total efficaciousness rates were 90 vs 92.6 vs 66.7 respectively in the three groups. The efficaciousness rate of the first two groups significantly differed from the third group (P < 0.01). However, no significant difference was shown between the first and second groups. It is concluded that the leukocyte count after the first course of chemotherapy may be an early indicator to predict the efficaciousness of chemotherapy.