Cell‐mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura

Zhang, Feng; Chu, Xiaoxia; Wang, Lin; Zhu, Yuanyuan; Li, Li-Zhen; Ma, Daoxin; Peng, Jun; Hou, Ming

doi:10.1111/j.1600-0609.2005.00622.x

Cited by 146 publications

(124 citation statements)

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“…20,21 In the present study, the supernatant concentrations and messenger RNA (mRNA) expression of granzyme A, granzyme B, and perforin were measured. Consistent with our previous study, 16 granzyme B and perforin were increased in the cytotoxic group compared with healthy controls. When IL-27 was added, a significant reduction in granzyme B expression was observed in the cytotoxic group, whereas no difference was observed in granzyme A or perforin ( Figure 2B-C).…”

Section: Resultssupporting

confidence: 81%

“…[2][3][4][5]13,16 In this study, the normal range of CTL-induced platelet apoptosis was established from the mean 6 2 standard deviations of results in healthy controls. The patients with CTL-induced platelet apoptosis higher than the upper limit of normal range were assigned to the cytotoxic group (23 patients); otherwise, they were assigned to the noncytotoxic group (15 patients) ( Figure 1).…”

Section: Resultsmentioning

confidence: 99%

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Interleukin 27 inhibits cytotoxic T-lymphocyte-mediated platelet destruction in primary immune thrombocytopenia

Zhou¹,

Qiu²,

Wang³

et al. 2014

Blood

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Key Points• IL-27 inhibits CTL cytotoxicity toward autologous platelets via decreasing granzyme B expression in ITP.Cytotoxic T-lymphocyte (CTL)-mediated platelet destruction and aberrant cytokine profiles play important roles in the pathogenesis of primary immune thrombocytopenia (ITP). Interleukin-27 (IL-27) has pleiotropic immunomodulatory effects. However, the effect of IL-27 on CTL activity in ITP has not been reported. In the present study, platelets from ITP patients were cultured with autologous CTLs in the presence of IL-27. We found that IL-27 could inhibit CTL-mediated platelet destruction. In these IL-27-treated CTLs, granzyme B and T-bet expression decreased significantly, whereas granzyme A, perforin, and eomesodermin were not affected. To further investigate the role of granzyme B in CTL-mediated platelet destruction, granzyme B inhibitor was added and platelet apoptosis was significantly inhibited. These results suggest that IL-27 negatively regulates CTL cytotoxicity toward platelets in ITP by decreasing granzyme B expression, which is associated with reduced T-bet expression. IL-27 may have a therapeutic role in treating ITP patients. (Blood. 2014;124(22):3316-3319)

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Section: Resultssupporting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Interleukin 27 inhibits cytotoxic T-lymphocyte-mediated platelet destruction in primary immune thrombocytopenia

Zhou¹,

Qiu²,

Wang³

et al. 2014

Blood

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“…The results confirmed our former finding that increasing cytotoxic T lymphocyte-mediated platelet lysis was the predominant cause of thrombocytopenia in ITP patients without platelet autoantibodies. 9,10 In addition, we also found rhBAFF could increase the production of IFN-␥ but had no obvious effect on the secretion of IL-4 in in vitro experiments, consistent with earlier studies showing typical Th1-mediated responses and reduced Th2-mediated responses in BAFF transgenic mice. 16 ITP is a heterogeneous disease; besides humoral immune abnormalities, several T-cell abnormalities have been demonstrated in patients with ITP, including Th1 bias, the inhibition of autologous megakaryocyte apoptosis by CD8 ϩ T cells, and cell-mediated cytotoxic lysis of platelets by CTLs.…”

Section: Discussionsupporting

confidence: 78%

“…16 ITP is a heterogeneous disease; besides humoral immune abnormalities, several T-cell abnormalities have been demonstrated in patients with ITP, including Th1 bias, the inhibition of autologous megakaryocyte apoptosis by CD8 ϩ T cells, and cell-mediated cytotoxic lysis of platelets by CTLs. 3,4,[8][9][10]35 Our results indicated that elevated BAFF not only was involved in humoral immune abnormalities by promoting the survival of B cells, but also may be involved in the cellular immunity abnormalities by promoting the survival of T cells.…”

Section: Discussionmentioning

confidence: 77%

“…1 The autoantibodies produced by autoreactive B cells against self-antigens, specifically immunoglobulin G (IgG) antibodies against glycoprotein IIb (GPIIb)/IIIa and/or GPIb/IX, are considered to play a crucial role. 2 In addition, several abnormalities involving the cellular mechanisms of immune modulation, such as the T helper 1 (Th1) bias, 3,4 the decreased number or defective suppressive function of regulatory T cells, 5-7 and the platelet destruction by cytotoxic T cells (CTLs), [8][9][10] have been described. The cause for these abnormalities remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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The effects of BAFF and BAFF-R-Fc fusion protein in immune thrombocytopenia

Zhu

Shi

Peng

et al. 2009

Blood

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IntroductionImmune thrombocytopenia (ITP) is an autoimmune disorder in which the patient's immune system is activated by platelet autoantigens resulting in immune-mediated platelet destruction and/or suppression of platelet production. 1 The autoantibodies produced by autoreactive B cells against self-antigens, specifically immunoglobulin G (IgG) antibodies against glycoprotein IIb (GPIIb)/IIIa and/or GPIb/IX, are considered to play a crucial role. 2 In addition, several abnormalities involving the cellular mechanisms of immune modulation, such as the T helper 1 (Th1) bias, 3,4 the decreased number or defective suppressive function of regulatory T cells, 5-7 and the platelet destruction by cytotoxic T cells (CTLs), [8][9][10] have been described. The cause for these abnormalities remains unknown. Moreover, the treatment regimens for ITP including glucorticosteroids, intravenous immunoglobulin G, anti-D, and splenectomy are not always effective, and only one-third of adult patients achieve long-term remission.B-cell activating factor (BAFF; also known as B-lymphocyte stimulator, tumor necrosis factor and apoptosis ligand-related leukocyte-expressed ligand 1, tumor necrosis factor homologue that activates apoptosis, nuclear factor B, and c-Jun NH 2 -terminal kinase, and tumor necrosis factor superfamily 13B) belonging to the family of tumor necrosis factor (TNF) ligands is critical for the maintenance of normal B-cell development, homeostasis, and autoreactivity 11,12 and T-cell costimulation. [13][14][15] In addition, BAFF also augments certain Th1-associated inflammatory responses. 16 BAFF binds to 3 receptors: B-cell maturation antigen (tumor necrosis factor receptor superfamily, member 17 [TNFRSF17]), transmembrane activator and calcium-modulating cyclophilin ligand (CAML) interactor (TACI; TNFRSF13B), and BAFF receptor (BR3/BAFF-R; TNFRSF13C). 17,18 BR3, identified as the crucial receptor for B-cell survival, is expressed on a wide range of B-cell subsets, including immature, transitional, mature, memory, and germinal center B cells, as well as on plasma cells. 19 Furthermore, BAFF binding to BR3 on T cells has been shown to costimulate T-cell proliferation both in vitro and in vivo. 15 Several lines of evidence suggested that BAFF may play an important role in autoimmunity. Autoantigen-binding B cells may have an increased dependence on the BAFF survival signal. 20 In addition, elevated BAFF plasma level was observed in many patients with autoimmune diseases such as rheumatoid arthritis (RA), 21 systemic lupus erythematosus (SLE), 22 Sjögren syndrome (SS), 23 and multiple sclerosis. 24 Inhibition of BAFF signaling is a potentially therapeutic option for treatment of B cell-mediated autoimmune conditions. Data from animal tests and clinical trials had proved that blockade of BAFF by blocking reagents (TACI-Ig, BAFF-R-Ig, BR3-Fc) was an effective therapeutic approach for some autoimmune diseases. [25][26][27] In our study, we focused on the effects of BAFF and BR3-Fc in ITP, and found recombinant human BAFF (r...

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Immune Thrombocytopenia

LeVine¹,

Brooks²

2022

Schalm's Veterinary Hematology

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Cell‐mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura

Cited by 146 publications

References 16 publications

Interleukin 27 inhibits cytotoxic T-lymphocyte-mediated platelet destruction in primary immune thrombocytopenia

Interleukin 27 inhibits cytotoxic T-lymphocyte-mediated platelet destruction in primary immune thrombocytopenia

The effects of BAFF and BAFF-R-Fc fusion protein in immune thrombocytopenia

Immune Thrombocytopenia

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