Immunoglobulins targeting both GPIIb/IIIa and GPIb/IX in chronic idiopathic thrombocytopenic purpura (ITP): evidence for at least two different IgG antibodies

Hou, Ming; Stockelberg, Dick; Kutti, Jack; Wadenvik, Hans

doi:10.1046/j.1365-2141.1997.1883006.x

Cited by 22 publications

(11 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of these antibodies are of the immunoglobulin (Ig) G class and are directed against glycoprotein IIb/IIIa and/or Ib/IX. [6][7][8][9][10] Platelet antibody complexes are cleared more rapidly by macrophages from the spleen and liver, resulting in thrombocytopenia. It remains to be elucidated what other critical factors play a role in the development of acute ITP such as the contribution of T-cell dysregulation and why some children go on to develop chronic autoimmune thrombocytopenia, whereas others remit.…”

Section: Epidemiology and Pathophysiologymentioning

confidence: 99%

Acute Idiopathic Thrombocytopenic Purpura of Childhood-Diagnosis and Therapy

Brousseau¹

2005

Pediatric Emergency Care

View full text Add to dashboard Cite

This CME activity is intended for physicians, nurse practitioners, and physician assistants who care for children who are ill or injured. Specialists including pediatricians, emergency physicians, pediatric emergency physicians, and family practitioners will find this information particularly useful. LEARNING OBJECTIVESAfter completion of this article, the reader will be able to: 1. Describe the pathophysiology of idiopathic thrombocytopenic purpura. 2. Recognize common bleeding manifestations of acute idiopathic thrombocytopenic purpura and learn the clinical grading scale used to estimate the severity of bleeding manifestations. 3. Discuss the management of acute idiopathic thrombocytopenic purpura and understand treatment strategies for life-threatening bleeding.I diopathic thrombocytopenic purpura (ITP) is an immunemediated illness that results in thrombocytopenia (platelet count <150 Â 10 9 /L) due to platelet destruction from autoantibodies. It is classified as acute or chronic in children depending on the duration of the illness. Acute ITP occurs most commonly in children between the ages of 1 and 10 years and resolves in less than 6 months. Chronic ITP, by definition, lasts longer than 6 months and more commonly occurs in children older than 9 years. Two recent studies reported that approximately half of children aged 10 to 18 years with acute ITP developed chronic ITP. 1,2 Overall, 75% of patients with acute ITP will have resolution of their thrombocytopenia with or without treatment 6 months after diagnosis.The presentation and management of a child with acute ITP are varied and dependent upon many factors, such as the age of the child and clinical symptoms at presentation. This review focuses on the diagnosis and management of acute ITP of childhood. EPIDEMIOLOGY AND PATHOPHYSIOLOGYThe annual incidence of acute ITP is estimated to be 2.5 to 5 per 100,000 children. 3,4 The peak age for presentation is 5.5 years. 3,5 There are some data supporting seasonal changes with a peak occurrence in the spring or early summer. 3,5 This seasonal variation may be linked to occurrence of viral illnesses during the same period. A history of a preceding viral illness is commonly associated with the development of acute ITP. The thrombocytopenia noted at presentation is severe, defined as a platelet count less than 20 Â 10 9 /L in more than 75% of patients. [3][4][5] The cause of ITP is unknown. Up to 50% to 80% of children with ITP will have antiplatelet antibodies that react with major membrane glycoproteins. 6 These antibodies are produced by B cell-derived plasma cells. Most of these antibodies are of the immunoglobulin (Ig) G class and are directed against glycoprotein IIb/IIIa and/or Ib/IX. 6-10 Platelet antibody complexes are cleared more rapidly by macrophages from the spleen and liver, resulting in thrombocytopenia. It remains to be elucidated what other critical factors play a role in the development of acute ITP such as the contribution of T-cell dysregulation and why some children go on to develop chronic au...

show abstract

Section: Epidemiology and Pathophysiologymentioning

confidence: 99%

Acute Idiopathic Thrombocytopenic Purpura of Childhood-Diagnosis and Therapy

Brousseau¹

2005

Pediatric Emergency Care

View full text Add to dashboard Cite

show abstract

“…[1][2][3][4][5] Antibody-mediated platelet destruction in the majority of ITP patients involves Fc-mediated phagocytosis by macrophages via the Fcg receptors (FcgRs). [2][3][4] One of the major activatory FcgRs implicated in platelet depletion is the FcgRIIIA, also a therapeutic target.…”

Section: Introductionmentioning

confidence: 99%

Monovalent Fc receptor blockade by an anti–Fcγ receptor/albumin fusion protein ameliorates murine ITP with abrogated toxicity

Menard

Prechl

et al. 2016

Blood

View full text Add to dashboard Cite

show abstract

“…18 Several platelet membrane targets for autoantibodies have been identifi ed, including GPIIb/IIIa and GPIb/IX, and it is currently accepted that thrombocytopenia in ITP is mediated by autoantibody-platelet binding. [19][20][21][22] Based on the monotonic nature of antibody-antigen binding, it is highly likely that platelet opsonization increases as a direct function of increasing concentrations of autoantibody in plasma. Consequently, it is not surprising that therapies that reduce autoantibody concentrations in plasma (eg, plasmapheresis, protein-A immunoadsorption) palliate thrombocytopenia in many ITP patients.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic effects of high-dose monoclonal antibody therapy in a rat model of immune thrombocytopenia

Jin

Tayab

Balthasar

2005

AAPS J

View full text Add to dashboard Cite

A BSTRACTIntravenous administration of pooled, polyvalent human immunoglobulin (IVIG) has been used for over 20 years as a therapy for immune thrombocytopenia (ITP). IVIG is available in limited quantities, and clinical preparations have been associated with the transfer of human pathogens. We have proposed that high-dose monoclonal antibody may be used in lieu of IVIG to achieve benefi cial effects in the treatment of ITP. The current study investigates the effects of high-dose monoclonal antibody therapy in a rat model of ITP. Hybridoma cells secreting a murine monoclonal antiplatelet antibody (7E3) and murine monoclonal anti-methotrexate IgG (AMI) were grown in serum-free media. Next, 7E3, 8 mg kg -1 , was administered intravenously to rats following pretreatment with saline or AMI (1 g kg -1 IV). AMI and 7E3 plasma concentrations were determined via enzyme-linked immunosorbent assay, and platelet count was determined with a Cell-Dyne hematology analyzer. Severe, transient thrombocytopenia was induced by 7E3. Platelet counts dropped to ~8% of initial values within 1 hour after 7E3 administration. AMI pretreatment dramatically affected 7E3-induced thrombocytopenia, signifi cantly altering the time course of thrombocytopenia ( P < .05) and signifi cantly decreasing the severity of 7E3-induced thrombocytopenia (ie, following AMI pretreatment, nadir platelet count was greater than 8-fold that of the control group, P < .05). In addition, AMI pretreatment induced a 57% increase in 7E3 clearance (1.13 ± 0.13 mL h -1 kg -1 vs 0.72 ± 0.08 mL h -1 kg -1 , P < .05). Consequently, high-dose monoclonal antibody therapy attenuated thrombocytopenia and produced a moderate increase in the clearance of antiplatelet antibodies in a rat model of ITP.

show abstract

Immunoglobulins targeting both GPIIb/IIIa and GPIb/IX in chronic idiopathic thrombocytopenic purpura (ITP): evidence for at least two different IgG antibodies

Cited by 22 publications

References 12 publications

Acute Idiopathic Thrombocytopenic Purpura of Childhood-Diagnosis and Therapy

Acute Idiopathic Thrombocytopenic Purpura of Childhood-Diagnosis and Therapy

Monovalent Fc receptor blockade by an anti–Fcγ receptor/albumin fusion protein ameliorates murine ITP with abrogated toxicity

Pharmacokinetic and pharmacodynamic effects of high-dose monoclonal antibody therapy in a rat model of immune thrombocytopenia

Contact Info

Product

Resources

About