Influences of antiplatelet autoantibodies on platelet function in immune thrombocytopenic purpura

Yanabu, Mutsumasa; Suzuki, Masahiko; Soga, Tetsuji; Sone, Naoaki; Nagata, Hirokazu; Nomura, Shosaku; Kokawa, Terutoshi; Yasunaga, Kōjirō

doi:10.1111/j.1600-0609.1991.tb00529.x

Cited by 32 publications

(13 citation statements)

References 26 publications

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“…These results are in contrast with the reported increased sensitivity of platelets, both, reticulated and older platelets, from patients with acute immune autoimmune thrombocytopenia to TRAP induced activation (36). Our data are, however, in line with the observed decreased response to ADP of donor platelets that have been mixed with sera from patients with cAITP (8, 10). The difference between the studied disease entities, namely acute (36) vs. chronic disease (8, 10 and this study), may at least in part explain the observed discrepancies.…”

Section: Discussionsupporting

confidence: 88%

“…Their presence was not correlated with platelet counts, or with the level of inducible platelet activation. It has been shown, however, that GPIIb/IIIa autoantibodies may inhibit ADP, while GPIb autoantibodies may impair Ristocetin induced aggregation of normal platelets (10). In the current study, detectable antibodies may have been too rare for their correlation with platelet activation.…”

Section: Discussionmentioning

confidence: 99%

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Agonist‐inducible platelet activation in chronic idiopathic autoimmune thrombocytopenia

Panzer¹,

Höcker²,

Rieger³

et al. 2007

European J of Haematology

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Agonist‐inducible platelet activation in chronic idiopathic autoimmune thrombocytopenia

Panzer¹,

Höcker²,

Rieger³

et al. 2007

European J of Haematology

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“…The antiplatelet antibodies in ITP may accelerate platelet clearance by Fc γ -receptor (Fc γ R)-bearing macrophages of the reticuloendothelial system, particularly those in the spleen. The autoantibodies in ITP patients may also affect platelet function, via effects on the binding of ligands (e.g., Fg and VWF) to platelet surface receptors [124, 125], which may further enhance the severity of bleeding in these patients. Furthermore, recent studies demonstrated that antiplatelet antibodies from ITP patients suppress megakaryocyte development and induce megakaryocyte apoptosis, thus inhibiting platelet production [121, 122, 126, 127].…”

Section: Pathogenesis Of Immune-mediated Thrombocytopeniamentioning

confidence: 99%

Crosstalk between Platelets and the Immune System: Old Systems with New Discoveries

et al. 2012

Advances in Hematology

126

102

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Platelets are small anucleate cells circulating in the blood. It has been recognized for more than 100 years that platelet adhesion and aggregation at the site of vascular injury are critical events in hemostasis and thrombosis; however, recent studies demonstrated that, in addition to these classic roles, platelets also have important functions in inflammation and the immune response. Platelets contain many proinflammatory molecules and cytokines (e.g., P-selectin, CD40L, IL-1β, etc.), which support leukocyte trafficking, modulate immunoglobulin class switch, and germinal center formation. Platelets express several functional Toll-like receptors (TLRs), such as TLR-2, TLR-4, and TLR-9, which may potentially link innate immunity with thrombosis. Interestingly, platelets also contain multiple anti-inflammatory molecules and cytokines (e.g., transforming growth factor-β and thrombospondin-1). Emerging evidence also suggests that platelets are involved in lymphatic vessel development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2. Besides the active contributions of platelets to the immune system, platelets are passively targeted in several immune-mediated diseases, such as autoimmune thrombocytopenia, infection-associated thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia. These data suggest that platelets are important immune cells and may contribute to innate and adaptive immunity under both physiological and pathological conditions.

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“…It has been reported that some anti-platelet autoantibodies in ITP patients stimulate platelets (39,40), and anti-GPIbα antibodies may activate platelets under certain circumstances in a murine model (31). As described above, enhanced fibrin formation and apoptosis/ necrosis were found in the placentas of mothers with anti-GPIbα antibodies.…”

Section: Anti-gpibα Antiserum Activated Antigen-positive Platelets Ementioning

confidence: 99%

“…Anti-GPIbα or preimmune serum (10 μl/g body weight) was injected into 3- to 4-week-old WT BALB/c mice, and then the injury of mesenteric arteriole was induced by ferric chloride. Thrombus formation was monitored for 40 …”

Section: Reagents Fitc-conjugated Goat Anti-mouse Igg Was Purchased mentioning

confidence: 99%

The maternal immune response to fetal platelet GPIbα causes frequent miscarriage in mice that can be prevented by intravenous IgG and anti-FcRn therapies

et al. 2011

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Fetal and neonatal immune thrombocytopenia (FNIT) is a severe bleeding disorder caused by maternal antibody-mediated destruction of fetal/neonatal platelets. It is the most common cause of severe thrombocytopenia in neonates, but the frequency of FNIT-related miscarriage is unknown, and the mechanism(s) underlying fetal mortality have not been explored. Furthermore, although platelet αIIbβ3 integrin and GPIbα are the major antibody targets in immune thrombocytopenia, the reported incidence of anti-GPIbα-mediated FNIT is rare. Here, we developed mouse models of FNIT mediated by antibodies specific for GPIbα and β3 integrin and compared their pathogenesis. We found, unexpectedly, that miscarriage occurred in the majority of pregnancies in our model of anti-GPIbα-mediated FNIT, which was far more frequent than in anti-β3-mediated FNIT. Dams with anti-GPIbα antibodies exhibited extensive fibrin deposition and apoptosis/necrosis in their placentas, which severely impaired placental function. Furthermore, anti-GPIbα (but not anti-β3) antiserum activated platelets and enhanced fibrin formation in vitro and thrombus formation in vivo. Importantly, treatment with either intravenous IgG or a monoclonal antibody specific for the neonatal Fc receptor efficiently prevented anti-GPIbα-mediated FNIT. Thus, the maternal immune response to fetal GPIbα causes what we believe to be a previously unidentified, nonclassical FNIT (i.e., spontaneous miscarriage but not neonatal bleeding) in mice. These results suggest that a similar pathology may have masked the severity and frequency of human anti-GPIbα-mediated FNIT, but also point to possible therapeutic interventions.

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Influences of antiplatelet autoantibodies on platelet function in immune thrombocytopenic purpura

Cited by 32 publications

References 26 publications

Agonist‐inducible platelet activation in chronic idiopathic autoimmune thrombocytopenia

Agonist‐inducible platelet activation in chronic idiopathic autoimmune thrombocytopenia

Crosstalk between Platelets and the Immune System: Old Systems with New Discoveries

The maternal immune response to fetal platelet GPIbα causes frequent miscarriage in mice that can be prevented by intravenous IgG and anti-FcRn therapies

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