The Largest Isoform of Platelet Membrane Glycoprotein Iba Is Commonly Distributed in Eastern Asian Populations

SummaryPlatelet membrane glycoprotein Iba has at least two polymorphisms which affect phenotype. One is the dimorphism at codon 145, and the other is a molecular weight polymorphism due to variable numbers of tandem repeats (TR) in the macroglycopeptide region. These two polymorphisms are in linkage disequilibrium. The frequencies of these polymorphisms differ considerably depending on race, and the largest variant with four TR is almost exclusively present in the Japanese population. We examined the genotypes of HPA-2 and TR polymorphism in three different races from Eastern Asia; the Japanese (n = 103), Korean (n = 101) and Chinese population (n = 177). The gene frequency of HPA-2 differed significantly among these three populations. Among HPA-2b-positive individuals, the A isoform with four TR and B with three TR were present in all three populations and A dominated over B. Individuals homozygous for the A isoform were found in both Japanese and Korean populations. These findings indicate that the largest haplotype is common in the Eastern Asian region.

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Characteristics of quinine- and quinidine-induced antibodies specific for platelet glycoproteins IIb and IIIa

Blood ◽

10.1182/blood.v77.12.2668.2668 ◽

1991 ◽

Vol 77 (12) ◽

pp. 2668-2676 ◽

Cited By ~ 63

Author(s):

GP Visentin ◽

PJ Newman ◽

RH Aster

Keyword(s):

Immune Response ◽

Platelet Membrane ◽

The Other ◽

Membrane Glycoprotein ◽

Igg Antibodies ◽

Drug Induced ◽

Disulfide Bonding ◽

Platelet Membrane Glycoprotein ◽

Drug Dependent

Abstract Recent studies have shown that antibodies characteristic of quinine- and quinidine-induced thrombocytopenia sometimes recognize the platelet membrane glycoprotein (GP) complex IIb/IIIa in addition to their well known target, GPIb/IX. We have investigated the frequency with which drug-induced antibodies bind to GPIIb/IIIa and the nature of their target epitopes. In studies of sera from 13 patients sensitive to quinidine or quinine, we found that 10 contained IgG antibodies specific for both GPIb/IX and GPIIb/IIIa, two reacted with GPIb/IX alone, and one reacted with GPIIb/IIIa alone. In all cases, the presence of drug was required for binding of IgG to target GPs. By immunoabsorption, we found that each of five polyspecific sera contained at least two different antibodies, one reactive with GPb/IX and the other with GPIIb/IIIa. Further studies with eight drug- dependent antibodies (DDAb) specific for GPIIb/IIIa showed that three recognized the GPIIb/IIIa complex only, one recognized GPIIb alone, and three recognized GPIIIa alone. The eighth serum appeared to bind to both GPIIIa alone and to an epitope determined by the GPIIb/IIIa complex. The three antibodies specific for GPIIIa alone also reacted with GPIIIa deglycosylated with endo-H, and with the major (61 Kd) fragment obtained by chymotryptic digestion of GPIIIa but failed to react with reduced GPIIIa. These findings demonstrate that, in drug- induced, immunologic thrombocytopenia, the anti-platelet immune response is typically directed against epitopes on both GPIb/IX and GPIIb/IIIa. The three DDAb we studied that were specific for GPIIIa alone recognize epitopes resistant to chymotrypsin and endo-H treatment that are dependent on intrachain disulfide bonding.

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Absence of the 145,000 Molecular Weight, Soluble Platelet Membrane Glycoprotein - Lack of Platelet Agglutination

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657067 ◽

1979 ◽

Vol 42 (05) ◽

pp. 1626-1629 ◽

Cited By ~ 2

Author(s):

Nils Olav Solum ◽

Inger Hagen ◽

Miroslav Peterka ◽

Torbjørn Gjemdal

Keyword(s):

Molecular Weight ◽

Factor Viii ◽

Human Platelets ◽

Platelet Membrane ◽

Membrane Glycoprotein ◽

Related Protein ◽

Giant Platelets ◽

Platelet Membrane Glycoprotein ◽

Human Factor Viii ◽

Bovine Factor

SummaryOne step in the function of platelets in hemostasis is their adhesion to subendothelial tissue. The human factor VIII related protein (von Willebrand factor) is considered to be involved in the adhesion phenomenon (Baumgartner et al. 1977). One manifestation of the protein-cell interaction can be observed as a platelet agglutination after addition to the human platelets of a combination of the human protein and the glycopeptide ristocetin, or after addition of the bovine protein alone. The bovine factor VIII related protein as such directly binds to the platelet membrane (Kirby and Sha May Tang 1977) and thus represents a simpler system than ristocetin plus the human cofactor which may have to interact with each other before excerting their effect on the platelet membrane. The present paper concerns the se.One of the characteristics of the agglutination of human platelets brought about by the bovine factor VIII related protein (as well as by ristocetin plus the human cofactor) is that it is independent of the energy metabolism and the internal organization of the platelet. One would therefore expect that modified platelets and platelet “ghosts” would agglutinate as long as certain structures on the outer cell surface are chemically and sterically intact. Because of the hydrophilic character of the carbohydrate side chains, the membrane glycoproteins are considered of special importance for cell contact phenomena. Thus it has already been known for some years that giant platelets of the Bernard-Soulier type which do not agglutinate with the bovine protein (Bithell et al. 1972), contain a reduced amount of sialic acid related to protein content and surface area (Grottum and Solum 1969), and show a reduced glycoprotein stain in the GP I region on SDS polyacrylamide gel electrophoresis (Nurden and Caen 1975).This paper presents five observations which support a working hypothesis stating that the presence on the platelet membrane of the 145,000 molecular weight, soluble platelet membrane glycoprotein called GPS or glycocalicin is a prerequisite to the agglutination of human platelets by bovine factor VIII related protein.

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Characteristics of quinine- and quinidine-induced antibodies specific for platelet glycoproteins IIb and IIIa

Blood ◽

10.1182/blood.v77.12.2668.bloodjournal77122668 ◽

1991 ◽

Vol 77 (12) ◽

pp. 2668-2676 ◽

Cited By ~ 4

Author(s):

GP Visentin ◽

PJ Newman ◽

RH Aster

Keyword(s):

Immune Response ◽

Platelet Membrane ◽

The Other ◽

Membrane Glycoprotein ◽

Igg Antibodies ◽

Drug Induced ◽

Disulfide Bonding ◽

Platelet Membrane Glycoprotein ◽

Drug Dependent

Recent studies have shown that antibodies characteristic of quinine- and quinidine-induced thrombocytopenia sometimes recognize the platelet membrane glycoprotein (GP) complex IIb/IIIa in addition to their well known target, GPIb/IX. We have investigated the frequency with which drug-induced antibodies bind to GPIIb/IIIa and the nature of their target epitopes. In studies of sera from 13 patients sensitive to quinidine or quinine, we found that 10 contained IgG antibodies specific for both GPIb/IX and GPIIb/IIIa, two reacted with GPIb/IX alone, and one reacted with GPIIb/IIIa alone. In all cases, the presence of drug was required for binding of IgG to target GPs. By immunoabsorption, we found that each of five polyspecific sera contained at least two different antibodies, one reactive with GPb/IX and the other with GPIIb/IIIa. Further studies with eight drug- dependent antibodies (DDAb) specific for GPIIb/IIIa showed that three recognized the GPIIb/IIIa complex only, one recognized GPIIb alone, and three recognized GPIIIa alone. The eighth serum appeared to bind to both GPIIIa alone and to an epitope determined by the GPIIb/IIIa complex. The three antibodies specific for GPIIIa alone also reacted with GPIIIa deglycosylated with endo-H, and with the major (61 Kd) fragment obtained by chymotryptic digestion of GPIIIa but failed to react with reduced GPIIIa. These findings demonstrate that, in drug- induced, immunologic thrombocytopenia, the anti-platelet immune response is typically directed against epitopes on both GPIb/IX and GPIIb/IIIa. The three DDAb we studied that were specific for GPIIIa alone recognize epitopes resistant to chymotrypsin and endo-H treatment that are dependent on intrachain disulfide bonding.

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Molecular Basis and Clinical Aspects of Hereditary Megakaryocyte and Platelet Membrane Glycoprotein Disorders

Hämostaseologie ◽

10.1055/s-0038-1656647 ◽

1996 ◽

Vol 16 (02) ◽

pp. 114-138 ◽

Cited By ~ 6

Author(s):

R. E. Scharf

Keyword(s):

Genetic Basis ◽

Molecular Mechanisms ◽

Molecular Genetic ◽

Platelet Membrane ◽

Clinical Aspects ◽

Membrane Glycoprotein ◽

Membrane Glycoproteins ◽

Membrane Expression ◽

Receptor Complexes ◽

Platelet Membrane Glycoprotein

SummarySpecific membrane glycoproteins (GP) expressed by the megakaryocyte-platelet system, including GPIa-lla, GPIb-V-IX, GPIIb-llla, and GPIV are involved in mediat-ing platelet adhesion to the subendothelial matrix. Among these glycoproteins, GPIIb-llla plays a pivotal role since platelet aggregation is exclusively mediated by this receptor and its interaction with soluble macromolecular proteins. Inherited defects of the GPIIb-llla or GPIb-V-IX receptor complexes are associated with bleeding disorders, known as Glanzmann's thrombasthenia, Bernard-Soulier syndrome, or platelet-type von Willebrand's disease, respectively. Using immuno-chemical and molecular biology techniques, rapid advances in our understanding of the molecular genetic basis of these disorders have been made during the last few years. Moreover, analyses of patients with congenital platelet membrane glycoprotein abnormalities have provided valuable insights into molecular mechanisms that are required for structural and functional integrity, normal biosynthesis of the glycoprotein complexes and coordinated membrane expression of their constituents. The present article reviews the current state of knowledge of the major membrane glycoproteins in health and disease. The spectrum of clinical bleeding manifestations and established diagnostic criteria for each of these dis-orders are summarized. In particular, the variety of molecular defects that have been identified so far and their genetic basis will be discussed.

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