Lan Dai

Effects of rapamycin combined with low dose prednisone in patients with chronic immune thrombocytopenia.

We conducted this randomized trial to investigate the efficacy and safety of rapamycin treatment in adults with chronic immune thrombocytopenia (ITP). Eighty-eight patients were separated into the control (cyclosporine A plus prednisone) and experimental (rapamycin plus prednisone) groups. The CD4+CD25+CD127low regulatory T (Treg) cells level, Foxp3 mRNA expression, and the relevant cytokines levels were measured before and after treatment. The overall response (OR) was similar in both groups (experimental group versus control group: 58% versus 62%, P = 0.70). However, sustained response (SR) was more pronounced in the experimental group than in the control group (68% versus 39%, P < 0.05). Both groups showed similar incidence of adverse events (7% versus 11%, P = 0.51). As expected, the low pretreatment baseline level of Treg cells was seen in all patients (P < 0.001); however, the experimental group experienced a significant rise in Treg cell level, and there was a strong correlation between the levels of Treg cells and TGF-beta after the treatment. In addition, the upregulation maintained a stable level during the follow-up phase. Thus, rapamycin plus low dose prednisone could provide a new promising option for therapy of ITP.

Efficacy of immunomodulatory therapy with all-trans retinoid acid in adult patients with chronic immune thrombocytopenia

INTRODUCTION Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. In adults, ITP is more likely to be chronic, requiring individualised treatment and management. Corticosteroids and splenectomy are the most common therapy for ITP. However, these routine approaches failed in these patients with chronic ITP. The aim of this study was to evaluate the efficacy of immunomodulatory therapy with all-trans retinoid acid (ATRA) in adult patients with chronic ITP. MATERIALS AND METHODS ATRA therapy was applied in a total of 35 patients with chronic ITP who failed with standard dose corticosteroids and/or splenectomy. The response ratio and the change of the T cell subsets including Th1, Th2, Th17 and Treg, were evaluated. RESULTS Complete response and overall response were observed in 10 (28.6%) and 19 patients (54.3%), respectively. Compared with the control group, a significant decreased level of Treg cells, IL-10 and Foxp3 expression were found in ITP patients. ATRA therapy could significantly increase the percentage of Treg cell, IL-10 level and Foxp3 expression. CONCLUSIONS Our findings indicate that ATRA therapy could induce significant changes of Treg cells to induce response in patients with chronic ITP.

Pulsatilla saponin A induces differentiation in acute myeloid leukemia in vitro

Objectives: To identify whether Pulsatilla saponin A (PsA), an active molecule extracted from Pulsatilla chinensis regel, can induce acute myeloid leukemia (AML) cells differentiate. Methods: PsA was isolated from P. chinensis, and its effects of differentiation induction on both AML cell lines and the primary leukemia cells were investigated. Results: Compared with the untreated control, PsA induced the differentiation of U937 cells, K562 cells and HL-60 cells, represented as the increased CD15+ cells in a dose- and time-dependent manner in all the three AML cell lines, after PsA treatment. As the same time, the cell morphology of these AML cells was changed correspondingly; the cytoplasm/nuclei ratio was increased, basophilic cytoplasm was decreased, and eccentric nucleus and granules were also observed. Also, the same effects of differentiation induction by PSA were confirmed in the primary leukemia cells. However, the specific MEK/ERK inhibitor U0126 effectively abrogated the differentiation induced by PsA in vitro. Conclusions: PsA can modify the differentiation activity of AML cells, probably though the MEK/ERK signaling pathway.

An inherited macrothrombocytopenic disorder with abnormal large granules

Inherited giant platelet syndromes are a heterogeneous group of rare bleeding disorders. In the current study, a patient was reported with prolonged bleeding time, thrombocytopenia and giant platelets. Both the patients red and white cell counts were normal without morphological abnormalities. The electron microscopy of platelets showed abnormal large electron-dense granules in the cytoplasm with exocytosis being easily observed. Her fathers platelets had the same abnormalities. The expression of glycoprotein (GP)Ib, GPIIb and GPIIIa on the surface of the patients platelets was normal, and her platelet aggregation in response to ADP and ristocetin was also normal. Immunogold probes combined to monoclonal antibodies against GPIIIa, P-selectin or CD63 could not identify any relationship between the aberrant structures and alpha granules or lysosomes of platelet. Serotonin level was normal in the platelets of the patient, indicating the electron opaque granules are not dense bodies. The morphological abnormalities of the platelets from the patient are clearly distinguishable from other hereditary giant platelet disorders. We propose that the abnormal large granules from the patients platelets probably represent a novel inherited thrombocytopenic disorder.

Altered circulating T follicular helper cells in patients with chronic immune thrombocytopenia

The present study aimed to illuminate the role of circulating T follicular helper (TFH) cells in patients diagnosed with chronic immune thrombocytopenia (cITP). Fifty-four patients with cITP and 30 age-matched healthy control subjects were enrolled in the present study. TFH cell frequencies, expression of CD4+ TFH cell-associated cytokines, including interleukin (IL)-2, IL-4, IL-10 and IL-21 and associated regulatory mRNA expression levels including Bcl-6, c-Maf, Blimp-1 and PD-1 pre- and post-treatment with intravenous immunoglobulin and corticosteroids, were detected by flow cytometry, ELISA and reverse transcription-quantitative polymerase chain reaction, respectively. TFH cell frequencies of patients were significantly higher compared with healthy controls pre-treatment (P<0.05). Following treatment, significantly decreased percentages of TFH cells were present in cITP responders (P<0.05). Correlation analysis revealed that the number of TFH cells was negatively correlated with the platelet count in the peripheral blood. Furthermore, analysis of inflammatory cytokines indicated significant differences in serum interleukin (IL)-21 and IL-10 between pretreated patients and healthy controls (P<0.05). Additionally, transcription factor B-cell lymphoma (Bcl)-6, c-Maf and programmed death-ligand (PD)-1 mRNA expression levels were significantly different between cITP patients prior to treatment and the healthy controls (P<0.05). However, the expression levels of Bcl-6, C-Maf and PD-1 mRNA were significantly changed post-treatment (P<0.05). These data demonstrated that circulating TFH cells and CD4+ TFH cell-associated cytokines may serve a role in cITP. The findings suggest that the overactivation of TFH cells may contribute to the immunopathogenesis of cITP, thus blocking the pathway of TFH cells may be reasonable for therapeutic intervention.