Renchi Yang

Abnormality of CD4+CD25+ regulatory T cells in idiopathic thrombocytopenic purpura

Objectives: The aim of this study was to explore the profile and function of CD4+CD25+ regulatory T cells (Treg cells) in idiopathic thrombocytopenic purpura (ITP) patients. Methods: Treg cell numbers were analyzed by flow cytometric analysis in peripheral blood mononuclear cells collected from healthy donors or patients with ITP. Quantification of cell proliferation was assayed by an enzyme‐linked immunosorbent assay kit, based on the measurement of BrdU incorporation during DNA synthesis. Results: The percentage of Treg cells was significantly decreased in ITP patients in active and non‐remission state(5.79 ± 1.22%) when compared with the patients in remission(11.63 ± 4.56%) and to healthy subjects(12.68 ± 3.59%). The suppressive activity of Treg cells in ITP patients was also found to be impaired. Conclusion: These results suggest that decreased number and function of Treg cells might be one of mechanisms that cause immune regulation dysfunction in ITP.

MicroRNA and leukemia: Tiny molecule, great function

MicroRNAs are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their targeted messenger RNAs (mRNAs). It is known that aberrant microRNA expression can play a vital role in the pathology of leukemia, thus microRNAs have rapidly emerged as potential targets for therapeutics. This review focuses on recent researches on the important roles of microRNAs in the pathogenesis of leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL).

Transplantation of umbilical cord blood-derived endothelial progenitor cells: a promising method of therapeutic revascularisation.

Abstract:  Therapeutic neovascularisation by endothelial progenitor cells (EPCs) mediated vascular regeneration is becoming a novel option for the treatment of ischaemic diseases. Recently, human umbilical cord blood (CB) has been found to contain a large number of EPCs and transplantation of CB EPCs led to a successful salvage of the ischaemic limbs through improvement in blood perfusion, indicating the feasibility of using CB cells for therapeutic revascularisation. This review will summarise recent studies in therapeutic revascularisation using CB cells and discuss the potential clinical utilisation of CB cells in ischaemic diseases.

Fetal BM-derived mesenchymal stem cells promote the expansion of human Th17 cells, but inhibit the production of Th1 cells

Th type 17 (Th17) cells have been identified as a proinflammatory T‐cell subset. Here, we investigated the regulation of human Th17 cells by fetal BM‐derived mesenchymal stem cells (FBM‐MSC). We cocultured FBM‐MSC with human PBMC or CD4+ T cells from healthy donors. FBM‐MSC significantly suppressed the proliferation of CD4+ T cells stimulated by PHA and recombinant IL‐2. Significantly higher levels of IL‐17 were observed in FBM‐MSC cocultured with either PBMC or CD4+ T cells than that in PBMC cultured alone or CD4+ T cells cultured alone. Flow cytometry analysis showed that the percentage of Th17 cells in coculture of FBM‐MSC and CD4+ T cells was significantly higher than that in CD4+ T‐cell cultured alone. FBM‐MSC did not express IL‐17 protein. Consistent with the augmentation of Th17 cells, significantly higher levels of IL‐6 and IL‐1 were observed in coculture of FBM‐MSC and CD4+ T cells than that in CD4+ T‐cell culture, while the levels of IL‐23 were similar between FBM‐MSC + PBMC coculture and PBMC alone, or FBM‐MSC + CD4+ T‐cell and CD4+ T‐cell alone. The presence of FBM‐MSC decreased the percentage of Th1 cells, but minimally affected the expansion of CD4+CD25+ T cells. In conclusion, our data demonstrate for the first time that FBM‐MSC promote the expansion of Th17 cells and decrease IFN‐γ‐producing Th1 cells. These data suggest that IL‐6 and IL‐1, instead of IL‐23, may be partly involved in the expansion of Th17 cells.

Hepatitis C virus-related adult chronic idiopathic thrombocytopenic purpura: experience from a single Chinese center

To the Editor: Chronic idiopathic thrombocytopenic purpura (ITP) is characterised by increased platelet destruction caused by antiplatelet autoantibodies that result in platelet phagocytosis by the reticuloendothelial system (RES) (1). Several reports, including one in the first issue of this journal, have shown a high prevalence of hepatitis C virus (HCV) infection in patients with chronic ITP (2–4). We report here our experience from a single center in China. Anti-HCV antibody (HCVab) was assayed in 247 chronic ITP patients referred to our hospital between 1992 and 2001; the clinical data were retrospectively analyzed. All patients fulfill the following criteria for chronic ITP: adult patients (‡18 yr old); isolated thrombocytopenia (<100 · 10/L) that had persisted for a minimum of 6 months; a normal or increased number of bone marrow megakaryocytes; absence of myelodysplastic features on bone marrow and lack of other known causes such as Systemic Lupus Erythematosus (SLE), etc. All patients were negative for anti-human immunodeficiency virus antibodies. Treatment response was defined as follows: (a) complete remission (increase in platelet count to ‡100 · 10/L); (b) partial or no response (platelet count <100 · 10/L). Data were analyzed by SPSS 10.0 for windows. P < 0.05 was considered statistically significant. As shown in Table 1, 33 of 247 (13.4%) patients were HCVab positive. Six patients (four males and two females) had developed hepatitis before ITP was diagnosed, and two of them had liver dysfunction. None had cirrhosis and/or splenomegaly according to abdominal ultrasound examinations. Of the remaining 27 patients, HCVab was not assayed until they were seen at our hospital, so that, we cannot exclude the possibility that in some patients, HCV might have been acquired after ITP developed. Potential source of HCV transmission in these patients included intravenous immunoglobulin concentrates (2) infused prior to our HCV studies. After one course treatment with steroid, platelet counts increased to above 100 · 10/L in 37.8% of HCVab-negative patients and 31.2% of HCVabpositive patients. Those who did not respond to steroid were treated with traditional Chinese medicine, vincristine or azathioprine. Splenectomy was performed in five of 33 (15.2%) HCVab-positive patients and 60/214 (28.0%) HCVab-negative patients. Relapsed postsplenectomy occurred in two of five (40%) HCVab-positive patients and in 21 of 60 (35%) HCVab-negative patients. These relapsed patients were treated with vincristine or azathioprine. There was no difference in clinical and laboratory data between HCVab negative and positive chronic ITP patients (P > 0.05). Similar to other reports (3–5), our data confirmed the high prevalence (13.4%) of HCV infection in chronic ITP patients, and this prevalence rate is significantly higher than that (2.2%) in general Chinese population in our country (6). Some studies have shown platelets carrying HCVRNA in HCV infection patients and that free HCV could bind to normal human platelets by the putative role of human CD81 as a receptor for HCV (7). HCV-RNA in platelet could replicate actively under some conditions such as the use of immunosuppressive agents (7). Bordin et al. reported that HCV might also depress platelet production, directly causing thrombocytopenia (8). The study of Li et al. suggested that megakaryoblasts are vunerable to HCV infection and HCV can replicate in these cells, hiding in them for years (9). Treatment of HCV-associated thrombocytopenia with recombinant a2b-interferon, an inhibitor of viral replication, could lead to an increase in platelet counts in HCV-positive thrombocytopenic patients, indicating indirectly that HCV might play an important role in thrombocytopenia (9, 10). The pathophysiologic relationship of HCV and platelet or megakaryocyte in HCVassociated thrombocytopenia needs to be further studied. Eur J Haematol 2003: 70: 196–197 Printed in UK. All rights reserved Copyright Blackwell Munksgaard 2003

BAFF and BAFF-R of peripheral blood and spleen mononuclear cells in idiopathic thrombocytopenic purpura.

BAFF (B-cell activating factor belonging to the TNF family) is an essential component of B-cell homeostasis, and is required for the normal survival and development of B cells. To further explore the role of this cytokine in the pathogenesis of idiopathic thrombocytopenic purpura (ITP), BAFF/BAFF-R (one of receptors of BAFF) expression levels were determined and the correlation between the clinical parameters and the BAFF expression levels was analyzed. A total of 57 patients with ITP were enrolled and 25 age and sex-matched healthy volunteers served as controls. Serum was obtained from 41 patients with ITP and 22 healthy volunteers and was analyzed with a commercial human soluble BAFF (sBAFF) ELISA kit. BAFF and BAFF-R mRNA expression of peripheral blood (PB) (n = 42) and splenocytes (SP) (n = 8) mononuclear cells (MNC) were determined by real-time quantitative PCR. The SPMNC of normal controls came from three hereditary spherocytosis patients who underwent splenectomy. The untreated patients with ITP had higher serum BAFF levels (Median 1430 pg/ml, Range: 534–5787 pg/ml) than those of normal controls (Median 1120 pg/ml, Range: 640–2376 pg/ml, p = 0.006) and treated ITP group (Median 662 pg/ml, Range 267–1265 pg/ml, p = 0.000). On the other hand, serum BAFF levels of treated patients with ITP were lower than those of normal controls (p = 0.001). There was a weak correlation (the Pearson correlation coefficient is − 0.242) between platelet count and BAFF (p = 0.064). However, BAFF levels did not correlate with platelet associated immunoglobulin or immunoglobulin levels. Moreover, the serum BAFF levels were not statistically different between acute and chronic ITP (p = 0.841). PBMNC of ITP had higher BAFF but not BAFF-R mRNA expression than that of normal controls. BAFF mRNA expression of SPMNC had a positive correlation with BAFF-R in ITP patients but not in PBMNC of normal controls and untreated ITP patients. The BAFF-R mRNA expression of SPMNC was shown to be 15.29 times higher than that of PBMNC in ITP. BAFF might contribute to autoimmunity and disease development in ITP. However, BAFF serum level must be carefully considered as a surrogate marker of disease activity in ITP.

Health-related quality of life measured by the Short Form 36 in immune thrombocytopenic purpura: a cross-sectional survey in China.

Objectives:  The aim of this study is to assess the quality of life (QoL) of Chinese adults with idiopathic thrombocytopenic purpura (ITP).

Retrospective analysis of 1312 patients with haemophilia and related disorders in a single Chinese institute.

Summary.  With 1.3 billion people, China has the largest population in the world, and therefore has the largest population of persons with haemophilia (PWH). As there is no national registry for haemophilia, it is difficult to ascertain how many PWH have actually been diagnosed. Between January 1983 and June 2002, 1312 patients with coagulation disorders were referred to our hospital, and 1190 patients were evaluable. Among them, 1069 (89.8%) patients had haemophilia, 68 had vWD, 20 had factor XI deficiency, 10 had acquired factor VIII inhibitor and 23 had other coagulation disorders. Of the 1069 PWH, 14.7% were unclassified, 38.4% severe, 35.7% moderate and 11.1% mild. If the unclassified cases were excluded, 45.1% were severe, 41.9% moderate and 13.0% mild. Twenty‐nine of the 68 vWD patients had vWF:Ag <5%, and subcategorized as type 3 vWD. Because vWF multimer analysis was not performed in our centre, the remaining vWD patients were not subdivided.

Normal ranges and genetic variants of antithrombin, protein C and protein S in the general Chinese population. Results of the Chinese Hemostasis Investigation on Natural Anticoagulants Study I Group

Background Inherited deficiency of antithrombin, protein C and protein S, three important, naturally occurring coagulation inhibitors, might play a major role in the occurrence of venous thromboembolism in Chinese. The establishment of age- and gender-related normal ranges of these inhibitors is crucial for an accurate diagnosis of these deficiencies. Design and Methods We designed a prospective cross-sectional study recruiting healthy adults from four university–affiliated hospitals in China. Antithrombin, protein C and protein S were studied by measuring their activity. Gene analysis was performed when natural anticoagulant deficiency was suspected. Polymorphisms of the factor V gene were searched for among subjects who were positive for activated protein C resistance. Results In 3493 healthy Chinese adults (1734 men, 1759 women; age 17–83 years), we found higher age-adjusted activities for protein C and protein S in men than in women but no sex difference for antithrombin. In women, mean protein C and protein S activities increased with age. In men, mean protein C levels increased with age up to the age of 49 but decreased after 50 years old; mean protein S levels decreased after 50 years of age. Antithrombin levels remained stable over time in women but decreased significantly after 50 years of age in men. Reference values according to age and sex allowed the identification of 15 genetic variants (protein C: 10, antithrombin: 3, protein S: 2) in subjects with protein activity below the 1st percentile. Conclusions This is the largest survey ever conducted in the healthy general Chinese population. These normal ranges provide the essential basis for the diagnosis and treatment of thrombosis in Chinese.

Analysis of calreticulin mutations in Chinese patients with essential thrombocythemia: clinical implications in diagnosis, prognosis and treatment.

Analysis of calreticulin mutations in Chinese patients with essential thrombocythemia: clinical implications in diagnosis, prognosis and treatment