Plasma levels and expression of interleukin-37 in patients with immune thrombocytopenia.

Interleukin (IL)-37 has an important role in autoimmune diseases by suppressing immunity and inflammation; however, the role of IL-37 in immune thrombocytopenia (ITP) has remained largely elusive. The present study aimed to investigate the expression of IL-37 and its potential role in the pathogenesis of ITP. The plasma levels and expression of IL-37 in the peripheral blood mononuclear cells of patients with active ITP, ITP patients in remission and healthy controls were measured by ELISA and reverse transcription-quantitative PCR, respectively. The levels of IL-37 in patients with ITP treated with and without glucocorticoids were also determined by ELISA. Specific anti-platelet glycoprotein (GP)IIb/IIIa and/or GPIb/IX autoantibodies were assayed by modified monoclonal antibody-specific immobilization of platelet antigens. The mean value of plasma IL-37 in ITP patients was slightly higher than that in healthy controls, but this was not statistically significant. There was no correlation between IL-37 and anti-platelet autoantibodies, and no significant difference in the IL-37 concentration was identified between patients treated with and without glucocorticoids. In addition, the correlation between IL-37 and the platelet count was analyzed, with no statistical significance observed. It was therefore concluded that IL-37 may not have a pivotal role in the development of ITP. However, the lack of significant differences may be due to the limited number of patients in different groups. A larger number of ITP patients should be enrolled in the future work and achieve more accurate results.

Weekly versus biweekly bortezomib given in patients with indolent non-Hodgkin lymphoma: A meta-analysis.

BACKGROUND: Bortezomib is recently studied as a novel agent in indolent lymphoma. The optimal schedule of bortezomib used in indolent lymphoma is still uncertain. METHODS: We did a systematic review and meta-analysis of the clinical trials comparing the efficacy and toxicity of the weekly and biweekly schedules of bortezomib in patients with indolent lymphoma. We searched Pubmed, Cochrane Library and Emabase from inception to July 29, 2016. The primary outcome was the overall response rate including the complete response rate and the partial response rate. The secondary outcomes were the proportions of patients in each group experiencing the adverse events including the neutropathy, fatigue, diarrhea, nausea and neutropenia. FINDINGS: After final screening, six trials were considered eligible for analysis. The results showed that the overall response rate of biweekly schedule was higher than that of weekly schedule in indolent lymphoma (OR 1.691;95%CI 1.02-2.80). Furthermore, there were no significant differences between the two schedules of bortezomib for the main adverse events. INTERPRETATION: The biweekly schedule of bortezomib was more effective than the weekly schedule in indolent lymphoma, with similar proportion of toxicities.

Methylprednisolone suppresses the Wnt signaling pathway in chronic lymphocytic leukemia cell line MEC-1 regulated by LEF-1 expression.

High dose methylprednisolone (HDMP) has been an effective salvage therapy for patients with relapsed chronic lymphocytic leukemia (CLL), while little is known about the exact mechanisms implicated in glucocorticoid-induced cell death. To explore the mechanism of glucocorticoid-induced cell death, we investigated the effect of HDMP on canonical Wnt signaling which emerged as a key pathway implicated in the pathogenesis of CLL. In this study, the human CLL cell line MEC-1 was incubated with various concentrations of methylprednisolone. Cell proliferation activity was detected by CCK8 assay, the apoptotic effect was evaluated by TUNEL assay. Western blot was used to detect active-caspase 3, and the key proteins in Wnt signaling pathway (LEF-1, ß-catenin). RT-PCR was performed to assess the mRNA levels of ß-catenin, LEF-1, c-myc and cyclin D1. We observed that high concentration of methylprednisolone could suppress the proliferation activity of MEC-1 cells, promote the relative expression of active-caspase 3, and induce apoptotic cell death. Furthermore, methylprednisolone could inhibit LEF-1 protein expression, consequently down-regulate mRNA levels of c-myc and cyclin D1, but could not affect the transcription level of ß-catenin and LEF-1 mRNA. The results of this study indicate that methylprednisolone can suppress Wnt signaling pathway by down-regulating LEF-1 protein expression, indicating a novel mechanism for HDMP therapy in CLL.

Expression of CD11a in lymphocyte subpopulation in immune thrombocytopenia.

Recent research demonstrates that the underlying mechanism in immune thrombocytopenia (ITP) is very complex. Lymphocyte function associated antigen-1 (LFA-1) plays important roles in autoimmune diseases. The purpose of this study was to investigate the expression of CD11a on lymphocytes and explore its possible role in ITP. The expression of CD11a on lymphocyte subpopulations (CD3(+) T cells, CD3(+)CD4(+) T cells, CD3(+)CD4(-) T cells, CD4(+)Foxp3(+) T regulatory cells and CD19(+) B cells) were analyzed by flow cytometry. Specific anti-platelet GPIIb/IIIa and/or GPIb/IX autoantibodies were assayed by modified monoclonal antibody specific immobilization of platelet antigens (MAIPA). The mean fluorescence intensity of CD11a on CD3(+) T, CD3(+)CD4(-) T and CD19(+) B lymphocytes were increased in ITP patients compared to healthy controls. No significant difference of CD11a expression on CD3(+)CD4(+) T cells or CD4(+)Foxp3(+) T regulatory cells was found between ITP patients and controls. Our data indicates the possible role of CD11a in the pathogenesis of ITP.

Reduced tumour necrosis factor receptor superfamily 13C inversely correlated with tumour necrosis factor superfamily 13B in patients with immune thrombocytopenia.

To investigate the expression of tumour necrosis factor superfamily 13B (TNFSF13B) receptors in immune thrombocytopenia (ITP) and their correlation with disease activity, we investigated the protein and mRNA levels of TNFSF13B, tumour necrosis factor receptor superfamily 13C (TNFRSF13C), TNFRSF13B and TNFRSF17 by flow cytometry, enzyme-linked immunosorbent assay and real time quantitative polymerase chain reaction. All CD19(+) B lymphocytes expressed TNFRSF13C by flow cytometry, but the mean fluorescence intensity (MFI) was decreased in patients with active disease compared to patients in remission and healthy controls, while no significant difference of TNFRSF13C mRNA was found between ITP patients and controls. The mRNA and plasma TNFSF13B were elevated in active ITP patients, and TNFRSF13C MFI level was inversely correlated with plasma TNFSF13B in active patients. In vitro assays showed that TNFRSF13C MFI was decreased after long exposure to TNFSF13B. No significant difference for TNFRSF13B or TNFRSF17 was found between ITP patients and controls. In conclusion, TNFRSF13C expression is reduced on CD19(+) cells in active ITP patients. This down-regulation occurs through a post-transcriptional mechanism and could be a consequence of chronic increase of TNFSF13B.

Metadherin contribute to BCR signaling in chronic lymphocytic leukemia.

We have reported Metadherin (MTDH) was proven to be overexpression and involved in malignance of chronic lymphocytic leukemia (CLL) via Wnt signaling pathway. In this study, we further investigate the role of MTDH in regulation of BCR signaling pathway in CLL. Six CLL samples whose cells were proliferation after BCR activation were chosen from patients with unmutated IgVH. CCK-8 method used to evaluate the proliferation rate. MTDH expression was measured by quantitative PCR and Western blot. After BCR activation, there exist upregulation of MTDH expression in mRNA and protein level in all six CLL patients (P<0.05). In cell line MEC-1, we observed the same pro-proliferation effect accompanying with elevated MTDH expression. The proliferation effects of BCR activation to MEC-1 can be inhibited by MTDH interference. The results of this study indicate that MTDH involved in the pro-proliferation effect of BCR activation in CLL. And the results imply that MTDH can be a potential therapy target of CLL.