Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA-4 and CX3CR1 (original) (raw)
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Doc 2 .(ITP) disease in light of advances in Immunology.doc
Abstract The mechanism of ITP historically has been linking to platelet autoantibody emission and an outcome of platelet destruction. Recent research reveals a multifactorial pathogenesis. Over the past decade, an immune process in autoimmunity has been established by identifying and depicting of immunoregulatory cell trafficking and elements. As a result, there is an understanding of an interplay of both cellular and humoral immune behavior in breaking down of self-tolerance thus a recognition of the destruction of platelets present in ITP to bring about a future attack by advancements in therapy. Failure of bone marrow implies a vital role towards ITP thrombocytopenia. In managing ITP, there are treatment tactics that aim at thrombopoietin receptor thus increase the level of platelet production. The activity incurs a cost efficient design.
Mechanisms of platelet recovery in ITP associated with therapy
Annals of Hematology, 2010
Immune thrombocytopenia (ITP) is an autoimmune disease primarily characterized by increased clearance of auto-antibody-sensitized platelets by Fc-receptor-bearing macrophages in the spleen and liver. It has been classically accepted that antibody-mediated platelet destruction is Fc dependent. Recent studies, however, may also indicate the involvement of Fc-independent pathways of platelet destruction. Current treatment options work by immunosuppression (e.g., corticosteroids), immunomodulation (e.g., IVIg and anti-D), or removal of the platelet destruction site (splenectomy) in ITP. This review will discuss the mechanisms of action of these and other treatments for ITP.
Experimental Hematology, 2006
Objective. Altered self-antigen processing/presentation of apoptotic cells by DCs and/or modifications of autoantigens may lead to the development of autoantibodies. Increasing evidence indicates that platelets may undergo apoptosis. Therefore, in the present study we investigated whether platelet apoptosis and/or dendritic cells (DCs) may play a role in the stimulation of the immuno-mediated anti-platelet response in chronic immune thrombocytopenic purpura (ITP). Methods and Results. Twenty-nine patients with active ITP and 29 healthy adult volunteers were enrolled into the study. Freshly washed platelets and platelets aged in a plasma-free buffer for 72 hours at 37 C were assessed by flow cytometry for phosphatidylserine exposure using annexin V-FITC, caspase activation, and platelet activation markers. CD14-derived DCs were characterized by immunophenotyping, cytokine production, and ability to present fresh and aged platelets to T lymphocytes. We demonstrated that platelets from ITP patients, either fresh or in vitro aged, show increased apoptosis (with low levels of activation) in comparison to their normal counterparts. We also found that immature DCs readily ingest apoptotic platelets. Furthermore, in ITP patients DCs, prepulsed with autologous/allogeneic fresh and aged platelets, are highly efficient in stimulating autologous T-cell proliferation as compared to DCs derived from healthy donors. This finding may be related to the upregulated expression of CD86 in DCs from ITP patients and not to higher phagocytic activity. Conclusion. These results suggest that DC dysfunction, together with increased propensity of platelets to undergo apoptosis, may play a role in the stimulation of the immune system in ITP. Ó
Functional properties of lymphocytes in idiopathic thrombocytopenic purpura
Human Immunology, 2001
Idiopathic or immune thrombocytopenic purpura (ITP) is characterized by antibody-mediated destruction of platelets. The etiology is unknown. We postulated that increased autoantibody production in ITP might be attributable to either increased or prolonged expression of CD40 ligand (CD40L, CD154) in T or B lymphocytes, as has been previously observed in systemic lupus erythematosus (SLE). In addition, we hypothesized that ITP is characterized by increased levels of interleukin 4 (IL-4), a prototypic Th2 cytokine which, along with CD40 ligation, is required for B cell differentiation and production of several IgG subclasses. Cell surface CD154 expression was measured in freshly-isolated and in vitroactivated peripheral blood lymphocytes of sixteen ITP patients and eight healthy volunteers. Plasma levels of IL-4 and the prototypic Th1 cytokine interferon-gamma (IFN␥) were determined. We observed that CD154 expression in unstimulated and in vitro-activated lymphocytes did not differ between ITP patients and healthy controls. Plasma levels of the Th2 cytokine IL-4 were significantly higher in the ITP patients. These studies indicate that overexpression of CD154 in lymphocytes is unlikely to be a primary pathophysiological defect in most patients with ITP. The data support that in addition to cell membrane antigens such as CD154, soluble cytokines such as IL-4 should be considered as potential targets for therapy in this disease.
The cellular immunology associated with autoimmune thrombocytopenic purpura: an update
Transfusion science, 1998
Chronic autoimmune thrombocytopenic purpura (AITP) is an organ specific autoimmune bleeding disease in which autoantibodies are directed against the individual's own platelets, resulting in increased Fc-mediated platelet destruction by macrophages in the reticuloendothelial system. Although AITP is primarily mediated by IgG auto-antibodies, their production is regulated by the influence of T lymphocytes and antigen presenting cells (APC). This review argues that enhanced T helper cell/antigen presenting cell interactions in patients with AITP may be responsible for IgG anti-platelet auto-antibody production. Understanding these cellular immune responses in AITP may lead to the development of more immune specific therapies for the management of this disease.
Clinical & Experimental Immunology, 2014
Immune thrombocytopenic purpura (ITP) is acquired autoimmune disease in children characterized by the breakdown of immune tolerance. This work is designed to explore the contribution of different lymphocyte subsets in acute and chronic ITP children. Imbalance in the T helper type 1 (Th1)/Th2 cytokine secretion profile was investigated. The frequency of T (CD3 + , CD4 + , CD8 +) and B (CD19 +) lymphocytes, natural killer (NK) (CD16 + 56 +) and regulatory T (Treg) [CD4 + CD25 +high forkhead box protein 3 (FoxP3) + ] cells was investigated by flow cytometry in 35 ITP children (15 acute and 20 chronic) and 10 healthy controls. Plasma levels of Th1 cytokines [interferon (IFN-γ) and tumour necrosis factor (TNF-α)] and Th2 [interleukin (IL)-4, IL-6 and IL-10)] cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The percentage of Treg (P < 0•001) and natural killer (NK) (P < 0•001) cells were significantly decreased in ITP patients compared to healthy controls. A negative correlation was reported between the percentage of Treg cells and development of acute (r = −0•737; P < 0•01) and chronic (r = −0•515; P < 0•01) disease. All evaluated cytokines (IFN-γ, TNF-α, IL-4, IL-6 and IL-10) were elevated significantly in ITP patients (P < 0•001, P < 0•05, P < 0•05, P < 0•05 and P < 0•001, respectively) compared to controls. In conclusion, our data shed some light on the fundamental role of immune cells and their related cytokines in ITP patients. The loss of tolerance in ITP may contribute to the dysfunction of Tregs. Understanding the role of T cell subsets will permit a better control of autoimmunity through manipulation of their cytokine network.
New concepts in pathogenesis of primary immune thrombocytopenia
Sohag Medical Journal
Primary immune thrombocytopenia (ITP) is a common condition characterized by a low peripheral platelet count (100000/L) caused by cell-mediated and humoral-mediated destruction of the platelet. Immunological tolerance to platelet antigens is lost in these patients. The main step in the pathogenesis includes the overactivation of T-cells, particularly T-helper cells, the release of various cytokines, and the interaction of autoantibodies with platelet surface antigens, which results in platelet destruction by the immune system in the spleen. The most common PLT antigens against which autoantibodies are directed are CD41 and CD61. These antigens are occupied by autoantibodies so there is decreased detection of these antigens on the surface of platelets. PD1 is an important negative stimulatory molecule of the immune system a member of the CD28/B7 family. ITP patients have considerably increased levels of PD-1 on CD4+Tcells in their peripheral blood than healthy people., indicating that the PD1 molecule plays an important role in illness etiology.
Roles of CD5+, CD19+, CD41a+, CD55+ and CD59+ in Chronic Immune Thrombocytopenic Purpura (ITP)
British Journal of Medicine and Medical Research, 2013
The aim of this study was to investigate of the roles of CD5 + and CD19 + on lymphocytes, CD5 + on B lymphocytes, CD41a + on platelets and CD55 + and CD59 + on erythrocytes in platelet destruction; and evaluate them according to the patient response status to steroid therapy and platelet counts in chronic immune thrombocytopenic purpura (ITP). Study Design: This study included 20 chronic ITP patients and 20 healthy controls. We investigated the roles of CD5 + and CD19 + expression on lymphocytes, CD5 + expression on B lymphocytes, CD41a + expression on platelets, and CD55 + and CD59 + expression on erythrocytes, as well as the platelet counts in healthy and chronic ITP patients. Additionally, these markers were evaluated according to the patient response status to steroid therapy and platelet counts. Place and Duration of Study: This study took place at
The ITP syndrome: pathogenic and clinical diversity
Blood, 2009
Immune thrombocytopenia (ITP) is mediated by platelet autoantibodies that accelerate platelet destruction and inhibit their production. Most cases are considered idiopathic, whereas others are secondary to coexisting conditions. Insights from secondary forms suggest that the proclivity to develop platelet-reactive antibodies arises through diverse mechanisms. Variability in natural history and response to therapy suggests that primary ITP is also heterogeneous. Certain cases may be secondary to persistent, sometimes inapparent, infections, accompanied by coexisting antibodies that influence outcome. Alternatively, underlying immune deficiencies may emerge. In addition, environmental and genetic factors may impact platelet turnover, propensity to bleed, and response to ITP-directed therapy. We review the pathophysiology of several common secondary forms of ITP. We suggest that primary ITP is also best thought of as an autoimmune syndrome. Better understanding of pathogenesis and tole...