Journal articles on the topic 'Human platelet antigens'
To see the other types of publications on this topic, follow the link: Human platelet antigens.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Human platelet antigens.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Kao, KJ, DJ Cook, and JC Scornik. "Quantitative analysis of platelet surface HLA by W6/32 anti-HLA monoclonal antibody." Blood 68, no. 3 (September 1, 1986): 627–32. http://dx.doi.org/10.1182/blood.v68.3.627.627.
Full textAbstract:
Abstract Class I molecules of human major histocompatibility complex (HLA) are the most important antigenic system in determining the survival of transfused platelets in alloimmunized patients. Platelets with reduced expression of a specific type of HLA antigen may escape specific anti- HLA antibody-mediated destruction. By using 125I-labeled Fab fragments of W6/32 anti-HLA monoclonal antibody and competitive protein binding assays, we measured the range of total HLA concentrations on platelets. In 12 individuals examined, the mean number of HLA-A, B, and C molecules per platelet was 81,587 +/- 20,016 (mean +/- SD); its range was between 54,782 to 116,185 molecules per platelet. After treatment with chloroquine, 79.9 +/- 7.0% (mean +/- SD, n = 6) of HLA antigens were removed from platelets as determined by binding of 125I-W6/32 Fab. A similar result was obtained when HLA antigens on chloroquine-treated platelets were evaluated with immunofluorescence flow cytometry. In contrast, chloroquine treatment did not remove integral membrane protein such as P1A1 antigens on platelets. The presence of HLA antigens in the chloroquine eluate of platelets could be demonstrated to contain HLA antigens similar in mol wts to intact class I molecules by an immunoblotting technique. These data suggest that 70% to 80% of platelet HLA antigens are adsorbed and that such HLA antigens are not proteolytic products of integral membrane class I molecules. The origin of the adsorbed platelet HLA-antigens remains to be determined.
2
Kao, KJ, DJ Cook, and JC Scornik. "Quantitative analysis of platelet surface HLA by W6/32 anti-HLA monoclonal antibody." Blood 68, no. 3 (September 1, 1986): 627–32. http://dx.doi.org/10.1182/blood.v68.3.627.bloodjournal683627.
Full textAbstract:
Class I molecules of human major histocompatibility complex (HLA) are the most important antigenic system in determining the survival of transfused platelets in alloimmunized patients. Platelets with reduced expression of a specific type of HLA antigen may escape specific anti- HLA antibody-mediated destruction. By using 125I-labeled Fab fragments of W6/32 anti-HLA monoclonal antibody and competitive protein binding assays, we measured the range of total HLA concentrations on platelets. In 12 individuals examined, the mean number of HLA-A, B, and C molecules per platelet was 81,587 +/- 20,016 (mean +/- SD); its range was between 54,782 to 116,185 molecules per platelet. After treatment with chloroquine, 79.9 +/- 7.0% (mean +/- SD, n = 6) of HLA antigens were removed from platelets as determined by binding of 125I-W6/32 Fab. A similar result was obtained when HLA antigens on chloroquine-treated platelets were evaluated with immunofluorescence flow cytometry. In contrast, chloroquine treatment did not remove integral membrane protein such as P1A1 antigens on platelets. The presence of HLA antigens in the chloroquine eluate of platelets could be demonstrated to contain HLA antigens similar in mol wts to intact class I molecules by an immunoblotting technique. These data suggest that 70% to 80% of platelet HLA antigens are adsorbed and that such HLA antigens are not proteolytic products of integral membrane class I molecules. The origin of the adsorbed platelet HLA-antigens remains to be determined.
3
Curtis, B. R., and J. G. McFarland. "Human platelet antigens - 2013." Vox Sanguinis 106, no. 2 (September 16, 2013): 93–102. http://dx.doi.org/10.1111/vox.12085.
Full text
4
Cooling, Laura L. W., Kathleen Kelly, James Barton, Debbie Hwang, Theodore A. W. Koerner, and John D. Olson. "Determinants of ABH expression on human blood platelets." Blood 105, no. 8 (April 15, 2005): 3356–64. http://dx.doi.org/10.1182/blood-2004-08-3080.
Full textAbstract:
AbstractPlatelets express ABH antigens, which can adversely effect platelet transfusion recovery and survival in ABH-incompatible recipients. To date, there has been no large, comprehensive study comparing specific donor factors with ABH expression on platelet membranes and glycoconjugates. We studied ABH expression in 166 group A apheresis platelet donors by flow cytometry, Western blotting, and thin layer chromatography relative to donor age, sex, A1/A2 subgroup, and Lewis phenotype. Overall, A antigen on platelet membranes, glycoproteins, and glycosphingolipids was linked to an A1 red blood cell (RBC) phenotype. Among A1 donors, platelet ABH varied significantly between donors (0%-87%). Intradonor variability, however, was minimal, suggesting that platelet ABH expression is a stable, donor-specific characteristic, with 5% of A1 donors typing as either ABH high- or low-expressers. Group A2 donors, in contrast, possessed a Bombay-like phenotype, lacking both A and H antigens. Unlike RBCs, ABH expression on platelets may be determined primarily by H-glycosyltransferase (FUT1) activity. Identification of A2 and A1 low expressers may increase the availability and selection of crossmatched and HLA-matched platelets. Platelets from group A2 may also be a superior product for patients undergoing A/O major mismatch allogeneic progenitor cell transplantation. (Blood. 2005;105:3356-3364)
5
Guo, Li, Sikui Shen, Jesse W. Rowley, Neal D. Tolley, Wenwen Jia, Bhanu Kanth Manne, Kyra N. McComas, et al. "Platelet MHC class I mediates CD8+ T-cell suppression during sepsis." Blood 138, no. 5 (April 25, 2021): 401–16. http://dx.doi.org/10.1182/blood.2020008958.
Full textAbstract:
Abstract Circulating platelets interact with leukocytes to modulate host immune and thrombotic responses. In sepsis, platelet-leukocyte interactions are increased and have been associated with adverse clinical events, including increased platelet–T-cell interactions. Sepsis is associated with reduced CD8+ T-cell numbers and functional responses, but whether platelets regulate CD8+ T-cell responses during sepsis remains unknown. In our current study, we systemically evaluated platelet antigen internalization and presentation through major histocompatibility complex class I (MHC-I) and their effects on antigen-specific CD8+ T cells in sepsis in vivo and ex vivo. We discovered that both human and murine platelets internalize and proteolyze exogenous antigens, generating peptides that are loaded onto MHC-I. The expression of platelet MHC-I, but not platelet MHC-II, is significantly increased in human and murine platelets during sepsis and in human megakaryocytes stimulated with agonists generated systemically during sepsis (eg, interferon-γ and lipopolysaccharide). Upregulation of platelet MHC-I during sepsis increases antigen cross-presentation and interactions with CD8+ T cells in an antigen-specific manner. Using a platelet lineage–specific MHC-I–deficient mouse strain (B2Mf/f-Pf4Cre), we demonstrate that platelet MHC-I regulates antigen-specific CD8+ T-cell proliferation in vitro, as well as the number and functional responses of CD8+ T cells in vivo, during sepsis. Loss of platelet MHC-I reduces sepsis-associated mortality in mice in an antigen-specific setting. These data identify a new mechanism by which platelets, through MHC-I, process and cross-present antigens, engage antigen-specific CD8+ T cells, and regulate CD8+ T-cell numbers, functional responses, and outcomes during sepsis.
6
Athanasou, N. A., J. Quinn, A. Heryet, and J. O. McGee. "Localization of platelet antigens and fibrinogen on osteoclasts." Journal of Cell Science 89, no. 1 (January 1, 1988): 115–22. http://dx.doi.org/10.1242/jcs.89.1.115.
Full textAbstract:
The antigenic phenotype of the human osteoclast, which is known to be derived from a circulating mononuclear precursor cell of haemopoietic origin, is controversial. Recent studies have shown that macrophage as well as megakaryocyte/platelet antigens are expressed by osteoclasts. In this study, we have sought to define, by immunohistochemistry, the nature and possible function of platelet antigens expressed by human osteoclasts in foetal and adult bone specimens. Monoclonal antibodies to platelet glycoprotein IIIa (gpIIIa) and CD9 antibodies stained osteoclasts in all bone specimens examined. Fibrinogen was also localized to the osteoclast membrane in foetal bone imprints. In addition, we found that CD9 and gpIIIa antibodies reacted weakly with monocytes in buffy coat smears. Antibodies to factor 8 and glycoproteins Ib and IIb/IIIa did not react with osteoclasts. These results show that osteoclasts, monocytes, macrophages, megakaryocytes and platelets possess common antigens and that fibrinogen is present on the surface of osteoclasts. By analogy with platelets, CD9 and gpIIIa may play a role in fibrinogen binding by osteoclasts. Possible mechanisms by which platelet antigens and fibrinogen binding could affect osteoclast function are proposed.
7
Metcalfe, P., N. A. Watkins, W. H. Ouwehand, C. Kaplan, P. Newman, R. Kekomaki, M. de Haas, et al. "Nomenclature of human platelet antigens." Vox Sanguinis 85, no. 3 (October 2003): 240–45. http://dx.doi.org/10.1046/j.1423-0410.2003.00331.x.
Full text
8
Wen, Ying-hao, and Ding-Ping Chen. "Human platelet antigens in disease." Clinica Chimica Acta 484 (September 2018): 87–90. http://dx.doi.org/10.1016/j.cca.2018.05.009.
Full text
9
Thurlow, P. J., L. Kerrigan, R. A. Harris, and I. F. McKenzie. "Analysis of human bone marrow with monoclonal antibodies." Journal of Histochemistry & Cytochemistry 33, no. 12 (December 1985): 1183–89. http://dx.doi.org/10.1177/33.12.2415573.
Full textAbstract:
In order to study the antigenic phenotype of different hemopoietic cells, we used a series of monoclonal antibodies to investigate normal bone marrow in a standard immunofluorescence assay. The antibodies detected the following antigens: HLA-ABC, beta 2-microglobulin (beta 2m), HLA-DR (Ia), a lymphocyte subset and specific antigen (T and B) HuLy-m2, m3, T lymphocyte antigen (HuLy-m1), lymphocyte T200 antigen (HuLy-m4), a viral-associated antigen (HuLy-m5), and platelet-specific glycoproteins IIb-IIIa (HuPl-m1). The following results were obtained: (a) normoblasts were weakly HLA-ABC+, beta 2m+ and Ia-; all other lymphocyte and platelet antigens were not detected. (b) Myeloid cells at all stages of differentiation (promyelocytes, myelocytes, metamyelocytes, and neutrophils) were HLA-ABC+; beta 2m+; HuLy-m1-, m2-, m3+/- (20%), m4+, m5+/- (20%); HuPl-m1-; in addition, promyelocytes and myelocytes were Ia+ but neutrophils and metamyelocytes were Ia-. (c) Lymphocytes were HLA-ABC+, beta 2m+, Ia+/- (20-30%), HuLy-m1+/- (40-50%), m2+/- (60-70%), m3+, m4+, m5+; Pl-m1-. (d) Platelets and megakaryocytes were HLA-ABC+; beta 2m+; Ia-; HuLy-m1+-, m2-, m3-, m4-, m5-, HuPl-m1+, and the putative "megakaryocyte precursors" were HuPl-m1+, Ia-, HuLy-m1-. The different cell types in bone marrow could readily be distinguished, particularly cells of the myeloid series (Ia and HuLy-m4, m5), lymphocytes (Ia and HuLy-m1, m2, m3), and platelets and their precursor cells (HuPl-m1). This simple method of defining cellular phenotypes in bone marrow has demonstrated the practicality of using monoclonal antibodies to identify marrow cells and should be of diagnostic value.
10
Enomoto, Takayuki, Hisako Maruoka, Sumio Hanagaki, Shoji Morita, Masuhiro Shimamura, Keiichi Hando, Ayako Ishijima, et al. "Pregnancy-induced Alloimmunization against Platelet Antigens. HLA and Human Platelet Antigens (HPA)." Journal of the Japan Society of Blood Transfusion 46, no. 5 (2000): 467–73. http://dx.doi.org/10.3925/jjtc1958.46.467.
Full text
11
De Reys, S., C. Blom, B. Lepoudre, PJ Declerck, M. De Ley, J. Vermylen, and H. Deckmyn. "Human platelet aggregation by murine monoclonal antiplatelet antibodies is subtype-dependent." Blood 81, no. 7 (April 1, 1993): 1792–800. http://dx.doi.org/10.1182/blood.v81.7.1792.1792.
Full textAbstract:
Abstract Twenty murine monoclonal antibodies (MoAbs) generated against different human platelet antigens induced clumping of human platelets in plasma and buffer. Whereas one MoAb could agglutinate platelets, clumping for 19 MoAbs was blocked by metabolic inhibitors, indicating that these induce platelet activation. Fifteen MoAbs were of IgG1, two of IgG2a, and two of IgG2b subtype. F(ab')2 fragments of these did not evoke an aggregatory response, but specifically inhibited aggregations by and binding of their respective intact MoAbs to platelets. Single-platelet counting technology indicated that the MoAbs bind through their antigen- binding and Fc domains mainly to the surface of the same platelet, rather than cause interplatelet-binding. Despite these similarities, the mechanism of action was nevertheless subtype-dependent. Aggregation induced by all IgG1 antibodies could consistently be prevented by blocking the Fc gamma II-receptor, whereas aggregations induced by all IgG2 antibodies still occurred with blocked Fc-receptor, provided functional complement was present. We therefore conclude that platelet activation by MoAb-binding is initiated by antigen recognition followed by an Fc domain-dependent step, which involves the Fc gamma II-receptor for IgG1-type MoAbs and complement-binding for IgG2-type MoAbs. Thus, antibodies of different subtypes can aggregate platelets via different pathways.
12
De Reys, S., C. Blom, B. Lepoudre, PJ Declerck, M. De Ley, J. Vermylen, and H. Deckmyn. "Human platelet aggregation by murine monoclonal antiplatelet antibodies is subtype-dependent." Blood 81, no. 7 (April 1, 1993): 1792–800. http://dx.doi.org/10.1182/blood.v81.7.1792.bloodjournal8171792.
Full textAbstract:
Twenty murine monoclonal antibodies (MoAbs) generated against different human platelet antigens induced clumping of human platelets in plasma and buffer. Whereas one MoAb could agglutinate platelets, clumping for 19 MoAbs was blocked by metabolic inhibitors, indicating that these induce platelet activation. Fifteen MoAbs were of IgG1, two of IgG2a, and two of IgG2b subtype. F(ab')2 fragments of these did not evoke an aggregatory response, but specifically inhibited aggregations by and binding of their respective intact MoAbs to platelets. Single-platelet counting technology indicated that the MoAbs bind through their antigen- binding and Fc domains mainly to the surface of the same platelet, rather than cause interplatelet-binding. Despite these similarities, the mechanism of action was nevertheless subtype-dependent. Aggregation induced by all IgG1 antibodies could consistently be prevented by blocking the Fc gamma II-receptor, whereas aggregations induced by all IgG2 antibodies still occurred with blocked Fc-receptor, provided functional complement was present. We therefore conclude that platelet activation by MoAb-binding is initiated by antigen recognition followed by an Fc domain-dependent step, which involves the Fc gamma II-receptor for IgG1-type MoAbs and complement-binding for IgG2-type MoAbs. Thus, antibodies of different subtypes can aggregate platelets via different pathways.
13
Simsek, S., and A. E. G. Kr von dem Borne. "Molecular Genetics of Human Platelet Antigens." Transfusion Medicine and Hemotherapy 21, no. 3 (1994): 29–33. http://dx.doi.org/10.1159/000223059.
Full text
14
Kuijpers, RW, WH Ouwehand, PM Bleeker, D. Christie, and AE von dem Borne. "Localization of the platelet-specific HPA-2 (Ko) alloantigens on the N- terminal globular fragment of platelet glycoprotein Ib alpha." Blood 79, no. 1 (January 1, 1992): 283–88. http://dx.doi.org/10.1182/blood.v79.1.283.283.
Full textAbstract:
Abstract The human platelet-specific alloantigens HPA-2a and HPA-2b (= Kob and Koa) together constitute a biallelic antigen system. The HPA-2 antigens have not, to date, been located on a particular platelet membrane molecule. Here, we describe the localization of these antigens on platelet glycoprotein (GP) Ib alpha. Platelets from two patients with the Bernard-Soulier syndrome (BSS) were HPA-2(a-,b-) in the immunofluorescence test with HPA-2 alloantibodies on chloroquine- treated platelets. With monoclonal antibody (MoAb) immobilization of platelet antigen assay (MAIPA), positive reactions were obtained only when MoAbs against the platelet GPIb/IX complex were used in combination with anti-HPA-2a or -2b alloantibodies and normal donor platelets. By immunoprecipitation under nonreducing and reducing conditions a protein of 160 Kd and 145 Kd, respectively, was precipitated by the anti-HPA-2a serum. A protein migrating identically to this was precipitated by anti-GPIb MoAb. Normal donor platelets became HPA-2(a-,b-) after elastase treatment, suggesting that anti-HPA- 2 antibodies bind to the N-terminal elastase-sensitive part of GPIb alpha. Anti-HPA-2a antibodies inhibited the ristocetin-induced agglutination of HPA-2a-positive platelets but not of HPA-2a-negative platelets, indicating that the epitopes recognized by these alloantibodies are localized in the proximity of the von Willebrand- factor-binding domain. Together, these data provide evidence that the HPA-2 alloantigens are located on the N-terminal globular elastase- sensitive part of GPIb alpha. Furthermore, we show that the recently described Siba antigen is probably identical to HPA-2a.
15
Kuijpers, RW, WH Ouwehand, PM Bleeker, D. Christie, and AE von dem Borne. "Localization of the platelet-specific HPA-2 (Ko) alloantigens on the N- terminal globular fragment of platelet glycoprotein Ib alpha." Blood 79, no. 1 (January 1, 1992): 283–88. http://dx.doi.org/10.1182/blood.v79.1.283.bloodjournal791283.
Full textAbstract:
The human platelet-specific alloantigens HPA-2a and HPA-2b (= Kob and Koa) together constitute a biallelic antigen system. The HPA-2 antigens have not, to date, been located on a particular platelet membrane molecule. Here, we describe the localization of these antigens on platelet glycoprotein (GP) Ib alpha. Platelets from two patients with the Bernard-Soulier syndrome (BSS) were HPA-2(a-,b-) in the immunofluorescence test with HPA-2 alloantibodies on chloroquine- treated platelets. With monoclonal antibody (MoAb) immobilization of platelet antigen assay (MAIPA), positive reactions were obtained only when MoAbs against the platelet GPIb/IX complex were used in combination with anti-HPA-2a or -2b alloantibodies and normal donor platelets. By immunoprecipitation under nonreducing and reducing conditions a protein of 160 Kd and 145 Kd, respectively, was precipitated by the anti-HPA-2a serum. A protein migrating identically to this was precipitated by anti-GPIb MoAb. Normal donor platelets became HPA-2(a-,b-) after elastase treatment, suggesting that anti-HPA- 2 antibodies bind to the N-terminal elastase-sensitive part of GPIb alpha. Anti-HPA-2a antibodies inhibited the ristocetin-induced agglutination of HPA-2a-positive platelets but not of HPA-2a-negative platelets, indicating that the epitopes recognized by these alloantibodies are localized in the proximity of the von Willebrand- factor-binding domain. Together, these data provide evidence that the HPA-2 alloantigens are located on the N-terminal globular elastase- sensitive part of GPIb alpha. Furthermore, we show that the recently described Siba antigen is probably identical to HPA-2a.
16
Scholz, Thomas, Uta Temmler, Siegfried Krause, Stan Heptinstall, and Wolfgang Lösche. "Transfer of Tissue Factor from Platelets to Monocytes: Role of Platelet-Derived Microvesicles and CD62P." Thrombosis and Haemostasis 88, no. 12 (2002): 1033–38. http://dx.doi.org/10.1055/s-0037-1613351.
Full textAbstract:
SummaryTissue factor (TF) is the most important initiator of intravascular coagulation. Platelets contribute to TF exposure on monocytes, but the mechanism is not completely understood. Here we examined the possibility that platelets may release TF that can be transferred to monocytes by platelet-derived microvesicles. When human citrated platelet-rich plasma was incubated with collagen there was an increase in the plasma levels of TF and CD62P. Incubation of plasma obtained from collagen-stimulated PRP with a sediment of red and white blood cells resulted in an increase in the number of monocytes that express TF, CD62P and the platelet-specific antigen CD42a on their surface. This transfer of platelet-derived antigens to monocytes was reduced when CD62P was blocked by a specific antibody or when platelet-derived microvesicles were removed from the plasma either by high speed centrifugation (17,500 X g for 30 min) or by filtration (pore size 0.2 µm). The data indicate that platelet-derived microvesicles that are released from collagen-stimulated platelets may carry TF, CD62P and CD42a and may transfer these antigens to the surface of monocytes. The interaction of platelet-derived microvesicles with monocytes and the transfer of TF to monocytes strongly depend on CD62P.
17
Fraser, JK, MF Leahy, and MV Berridge. "Expression of antigens of the platelet glycoprotein IIb/IIIa complex on human hematopoietic stem cells." Blood 68, no. 3 (September 1, 1986): 762–69. http://dx.doi.org/10.1182/blood.v68.3.762.762.
Full textAbstract:
Abstract Several cell surface and cytoplasmic markers specific for the megakaryocyte-platelet lineage have been described. However, as yet, none of these has been shown to be expressed on cells earlier than the committed megakaryocyte progenitor, CFU-Meg. The present study was aimed at determining whether platelet lineage antigens could be detected on human pluripotential stem cells. Rabbit antiserum against human platelets (APS) was extensively absorbed with erythrocytes and either platelets, neutrophils, monocytes, or cells of the monocytic cell line U937. The anti-stem cell antibodies in each absorbed antiserum were determined using a complement-dependent cytotoxic assay for the pluripotential stem cell CFU-mix. Platelets alone removed anti- stem cell antibodies from APS. Absorption of APS with platelets from a patient with Glanzmann's thrombasthenia failed to remove the anti-stem cell activity, providing evidence for involvement of the platelet glycoprotein IIb/IIIa complex. Antiserum against purified glycoprotein IIb and against glycoprotein IIIa also recognized stem cells, resulting in reduced formation of mixed colonies. Absorption of these antisera with normal platelets removed the anti-stem cell activity, indicating that both IIb and IIIa are represented on stem cells. Hence, cell surface antigens specific for the stem cell-megakaryocyte-platelet pathway are expressed on the platelet glycoprotein IIb/IIIa complex.
18
Fraser, JK, MF Leahy, and MV Berridge. "Expression of antigens of the platelet glycoprotein IIb/IIIa complex on human hematopoietic stem cells." Blood 68, no. 3 (September 1, 1986): 762–69. http://dx.doi.org/10.1182/blood.v68.3.762.bloodjournal683762.
Full textAbstract:
Several cell surface and cytoplasmic markers specific for the megakaryocyte-platelet lineage have been described. However, as yet, none of these has been shown to be expressed on cells earlier than the committed megakaryocyte progenitor, CFU-Meg. The present study was aimed at determining whether platelet lineage antigens could be detected on human pluripotential stem cells. Rabbit antiserum against human platelets (APS) was extensively absorbed with erythrocytes and either platelets, neutrophils, monocytes, or cells of the monocytic cell line U937. The anti-stem cell antibodies in each absorbed antiserum were determined using a complement-dependent cytotoxic assay for the pluripotential stem cell CFU-mix. Platelets alone removed anti- stem cell antibodies from APS. Absorption of APS with platelets from a patient with Glanzmann's thrombasthenia failed to remove the anti-stem cell activity, providing evidence for involvement of the platelet glycoprotein IIb/IIIa complex. Antiserum against purified glycoprotein IIb and against glycoprotein IIIa also recognized stem cells, resulting in reduced formation of mixed colonies. Absorption of these antisera with normal platelets removed the anti-stem cell activity, indicating that both IIb and IIIa are represented on stem cells. Hence, cell surface antigens specific for the stem cell-megakaryocyte-platelet pathway are expressed on the platelet glycoprotein IIb/IIIa complex.
19
Berridge, MV, SJ Ralph, and AS Tan. "Cell-lineage antigens of the stem cell-megakaryocyte-platelet lineage are associated with the platelet IIb-IIIa glycoprotein complex." Blood 66, no. 1 (July 1, 1985): 76–85. http://dx.doi.org/10.1182/blood.v66.1.76.76.
Full textAbstract:
Abstract The stem cell-platelet lineage is uniquely defined by platelet cell- lineage antigens. These antigens are present on all stem cells measured by the spleen colony assay and become restricted to the platelet cell lineage as differentiation proceeds. In this study, anti-platelet serum (APS) has been used to identify cells in the bone marrow that express platelet cell-lineage antigens and to identify platelet cell surface molecules expressing these antigens. Anti-platelet IgG extensively absorbed with brain, thymus, and peritoneal cells bound selectively to stem cells, megakaryocyte progenitor cells (Mk-CFC), and megakaryocytes in CBA mouse bone marrow and to blood platelets. No other hemopoietic cell type, tissue, cell line, or tumor cell bound significant amounts of antibody against platelet cell-lineage antigens as determined by ability to absorb the anti-stem cell activity in APS. Studies with lactoperoxidase-labeled platelets showed that two major iodinated proteins of Mr = 114,000 and 138,000 were immunoprecipitated with APS and with antiserum that had been extensively absorbed. These proteins correspond to the platelet IIb-IIIa glycoprotein complex, which is known to express receptors for collagen and fibrinogen, molecules known to influence hemopoietic cell proliferation and tumor cell growth. A panel of six monoclonal antibodies against human IIb-IIIa inhibited spleen colony formation by 17% to 100%, J15 and A5.15 also being cytotoxic for granulocyte-macrophage progenitor cells and Mk-CFC. Other platelet monoclonal antibodies did not inhibit spleen colony formation. Although APS inhibited fibrinogen binding to platelets and platelet aggregation, these activities were greatly reduced with absorbed antiserum. Furthermore, fibrinogen treatment of bone marrow did not block the anti-stem cell activity in APS. Thus the evidence is consistent with expression of platelet cell-lineage antigens on the platelet IIb-IIIa glycoprotein complex at a site removed from the fibrinogen binding site.
20
Berridge, MV, SJ Ralph, and AS Tan. "Cell-lineage antigens of the stem cell-megakaryocyte-platelet lineage are associated with the platelet IIb-IIIa glycoprotein complex." Blood 66, no. 1 (July 1, 1985): 76–85. http://dx.doi.org/10.1182/blood.v66.1.76.bloodjournal66176.
Full textAbstract:
The stem cell-platelet lineage is uniquely defined by platelet cell- lineage antigens. These antigens are present on all stem cells measured by the spleen colony assay and become restricted to the platelet cell lineage as differentiation proceeds. In this study, anti-platelet serum (APS) has been used to identify cells in the bone marrow that express platelet cell-lineage antigens and to identify platelet cell surface molecules expressing these antigens. Anti-platelet IgG extensively absorbed with brain, thymus, and peritoneal cells bound selectively to stem cells, megakaryocyte progenitor cells (Mk-CFC), and megakaryocytes in CBA mouse bone marrow and to blood platelets. No other hemopoietic cell type, tissue, cell line, or tumor cell bound significant amounts of antibody against platelet cell-lineage antigens as determined by ability to absorb the anti-stem cell activity in APS. Studies with lactoperoxidase-labeled platelets showed that two major iodinated proteins of Mr = 114,000 and 138,000 were immunoprecipitated with APS and with antiserum that had been extensively absorbed. These proteins correspond to the platelet IIb-IIIa glycoprotein complex, which is known to express receptors for collagen and fibrinogen, molecules known to influence hemopoietic cell proliferation and tumor cell growth. A panel of six monoclonal antibodies against human IIb-IIIa inhibited spleen colony formation by 17% to 100%, J15 and A5.15 also being cytotoxic for granulocyte-macrophage progenitor cells and Mk-CFC. Other platelet monoclonal antibodies did not inhibit spleen colony formation. Although APS inhibited fibrinogen binding to platelets and platelet aggregation, these activities were greatly reduced with absorbed antiserum. Furthermore, fibrinogen treatment of bone marrow did not block the anti-stem cell activity in APS. Thus the evidence is consistent with expression of platelet cell-lineage antigens on the platelet IIb-IIIa glycoprotein complex at a site removed from the fibrinogen binding site.
21
Lim, C., D. P. Manage, A. Atrazhev, G. Denomme, C. J. Backhouse, and J. P. Acker. "Microfluidic approach to genotyping human platelet antigens." IET Nanobiotechnology 6, no. 2 (2012): 33. http://dx.doi.org/10.1049/iet-nbt.2011.0044.
Full text
22
Castro, Vagner. "Human platelet antigens and primary immune thrombocytopenia." Revista Brasileira de Hematologia e Hemoterapia 39, no. 2 (April 2017): 95–97. http://dx.doi.org/10.1016/j.bjhh.2017.02.008.
Full text
23
SONE, Naoaki, Kazuyuki YAMAGUCHI, Masahiko SUZUKI, Mutumasa YANABU, Tetsuji SOGA, Shosaku NOMURA, Hirokazu NAGATA, Terutoshi KOKAWA, and Kojiro YASUNAGA. "Some Monoclonal Anti-human-platelet Antibodies Recognize Dog Platelets as Antigens." Japanese Journal of Thrombosis and Hemostasis 1, no. 6 (1990): 482–88. http://dx.doi.org/10.2491/jjsth.1.482.
Full text
24
Garraud, Olivier, Fabrice Cognasse, and Pierre Moncharmont. "Immunological Features in the Process of Blood Platelet-Induced Alloimmunisation, with a Focus on Platelet Component Transfusion." Diseases 7, no. 1 (January 14, 2019): 7. http://dx.doi.org/10.3390/diseases7010007.
Full textAbstract:
Alloimmunisation to platelet antigens is not uncommon; a large number of females, having had pregnancies, developed antibodies to Human Leukocyte Antigen (HLA) moieties harboured on their foetuses’ cells (inherited from the father(s)) that may conflict with further pregnancies and transfused Platelet Components occasionally. This is possible since platelets constitutionally express HLA class I molecules (though in copy numbers that consistently differ among individuals). Platelets also express HPA moieties that are variants of naturally expressed adhesion and aggregation molecules; HPA differences between mothers and foetuses and between donors and recipients explain alloimmune conflicts and consequences. Lastly, platelets express ABO blood group antigens, which are rarely immunising, however transfusion mismatches in ABO groups seem to be related to immunisation in other blood and tissue groups. Transfusion also brings residual leukocytes that may also immunise through their copious copy numbers of HLA class I (rarely class II on activated T lymphocytes, B cells, and dendritic cells). In addition, residual red blood cells in platelet concentrates may induce anti-red blood cell allo-antibodies. This short review aims to present the main mechanisms that are commonly reported in alloimmunisation. It also critically endeavours to examine paths to either dampen alloimmunisation occurrences or to prevent them.
25
STANLEY, R. G., J. R. NGAIZA, E. ATIENO, G. JELL, K. FRANCKLOW, C. L. JACKSON, H. PARRY, and M. J. DOENHOFF. "Immune-dependent thrombocytopaenia in mice infected with Schistosoma mansoni." Parasitology 126, no. 3 (March 2003): 225–29. http://dx.doi.org/10.1017/s0031182002002858.
Full textAbstract:
As has been shown previously, immunologically intact mice with patent Schistosoma mansoni infections has a significantly lower mean platelet number than intact uninfected mice (P<0·0001). However, platelet numbers in T-cell deprived mice with patent infections were not significantly different from those in uninfected T-cell deprived mice. Also, platelet counts in both the infected and uninfected T-cell deprived groups were not significantly different from those in intact uninfected mice. The S. mansoni-induced thrombocytopaenia in mice is thus seemingly immune dependent. Immunologically intact mice with chronic 12-week-old S. mansoni infections has IgG antibodies that were reactive in an ELISA-type assay wit whole fixed platelets of both mouse and human origin. In Western immunoblots the IgG antibodies from chronically-infected mice reacted in particular against mouse and human platelet antigens of 90, 37 and 30 kDa. Antisera raised from 2 rabbits, immunized respectively with mouse and human platelet antigens, cross-reacted with antigens of the larval, adult worm and egg stages of S. mansoni. These results support the hypothesis that an anti-platelet antibody response may be the cause of the thrombocytopaenia observed in mice with patent schistosome infections.
26
Gruel, Y., B. Boizard, F. Daffos, F. Forestier, J. Caen, and JL Wautier. "Determination of platelet antigens and glycoproteins in the human fetus." Blood 68, no. 2 (August 1, 1986): 488–92. http://dx.doi.org/10.1182/blood.v68.2.488.bloodjournal682488.
Full textAbstract:
The autosomal recessive transmission of Glanzmann's thrombasthenia (GT) and Bernard-Soulier syndrome (BSS), together with requests of families who already had children with these diseases, prompted us to investigate the feasibility of their antenatal diagnosis. The preliminary step leading to the early detection of GT or BSS was to characterize, in the normal human fetus, the platelet antigens and glycoproteins (GPs) and to define their normal amounts on the membrane surface. Blood samples from 32 fetuses between 18 to 26 weeks of gestation were collected by direct puncture of the umbilical vein using an ultrasound-guided needle. Polyclonal antibodies from human origin directed against PLA1, Leka antigens, and the GPIIb IIIa complex (IgGL), or murine monoclonal antibodies specific for GPIb (AN51, 6D1), GPIIIa (AP-3), or GPIIb IIIa (AP-2) were studied using platelet suspension immunofluorescence tests. The binding of each antibody was quantified using a cytofluorograph (Ortho 50H). PLA1 and Leka antigens were expressed in normal amounts on fetal platelets as early as 16 weeks of intrauterine life. The GPIIb IIIa complex quantified by polyclonal or monoclonal antibodies was in the same range in fetuses (IgGL = 427 +/- 23 AUF, AP-2 = 459.5 +/- 8.5; AP-3 = 536 +/- 14) and in adults (IgGL = 420 +/- 30; AP-2 = 498 +/- 11; AP-3 = 515 +/- 13). The platelet binding of antibodies that recognized GPIb was higher in fetuses (AN51 = 491.5 +/- 14; 6D1 = 479 +/- 15) than in adults (AN51 = 426.5 +/- 9; 6D1 = 449 +/- 8.7). These results suggest that immunological techniques can be applied as early as 18 weeks of gestation for the antenatal diagnosis of GT and BSS.
27
Ghevaert, Cedric, David A. Wilcox, Juan Fang, Kathryn Armour, Mike R. Clark, Willem H. Ouwehand, and Lorna M. Williamson. "Recombinant Human HPA-1A Antibodies for Treatment of Fetomaternal Alloimmune Thrombocytopenia (FMAIT): Proof of Principle in An in Vivo Murine Model and Human Volunteer Studies." Blood 112, no. 11 (November 16, 2008): 85. http://dx.doi.org/10.1182/blood.v112.11.85.85.
Full textAbstract:
Abstract Fetomaternal alloimmune thrombocytopenia (FMAIT) is caused by maternal generation of antibodies specific for paternal platelet antigens and can lead to fetal intracranial hemorrhage. A single nucleotide polymorphism (SNP) in the gene encoding integrin β3 causes a clinically important maternal-paternal antigenic difference; Leu33 generates the human platelet antigen 1a (HPA-1a), whereas Pro33 generates HPA-1b. As a potential treatment to prevent fetal intracranial hemorrhage in HPA-1a alloimmunized pregnancies, we generated an antibody that blocks the binding of maternal HPA-1a–specific antibodies to fetal HPA-1a1b platelets by combining a high-affinity human HPA-1a–specific scFv (B2) with an IgG1 constant region modified to minimize Fcγ receptor–dependent platelet destruction (G1Δnab). B2G1Δnab saturated HPA-1a+ platelets at micromolar concentration and substantially inhibited binding of clinical HPA-1a–specific sera to HPA-1a+ platelets. The response of monocytes to B2G1Δnab-sensitized platelets was substantially less (<15%) than their response to unmodified B2G1, as measured by chemiluminescence. In addition, B2G1Δnab inhibited chemiluminescence induced by B2G1 and HPA-1a–specific sera. We set out to prove the principle of our strategy in vivo using a murine model. Beta3-deficient mice (WT) were transplanted with littermate bone marrow transduced with a lentiviral vector containing the human ITGB3 encoding either Leucine-33 or Proline-33. B2G1 and polyclonal Ig preparations from clinical HPA-1a–specific sera reduced circulating HPA-1a+ platelets, concomitant with transient thrombocytopenia whilst WT mice and HPA-1b+ mice remained unaffected. Given the differences between murine and human Fcγ receptors, F(ab)2 B2G1 was used as a non-destructive proof of principle blocking antibody and prevented the in vivo platelet destruction seen with B2G1 and polyclonal HPA-1a–specific antibodies. These results provide rationale for human clinical studies, which are now underway. Eight HPA-1a1b heterozygotes volunteers have been recruited and from each of them we generate 2 pools of autologous platelets. Each pool is sensitized with either B2G1 or B2G1Δnab and radiolabeled with either Cr-51 or In-111. After re-injection into the volunteer, platelet survival is followed by the means of the radiolabel in order to show the differential effect on platelet destruction of the G1Δnab constant region when compared to the reference IgG1 destructive antibody. Full data of the volunteer studies will be presented in support of further clinical trials.
28
Gruel, Y., B. Boizard, F. Daffos, F. Forestier, J. Caen, and JL Wautier. "Determination of platelet antigens and glycoproteins in the human fetus." Blood 68, no. 2 (August 1, 1986): 488–92. http://dx.doi.org/10.1182/blood.v68.2.488.488.
Full textAbstract:
Abstract The autosomal recessive transmission of Glanzmann's thrombasthenia (GT) and Bernard-Soulier syndrome (BSS), together with requests of families who already had children with these diseases, prompted us to investigate the feasibility of their antenatal diagnosis. The preliminary step leading to the early detection of GT or BSS was to characterize, in the normal human fetus, the platelet antigens and glycoproteins (GPs) and to define their normal amounts on the membrane surface. Blood samples from 32 fetuses between 18 to 26 weeks of gestation were collected by direct puncture of the umbilical vein using an ultrasound-guided needle. Polyclonal antibodies from human origin directed against PLA1, Leka antigens, and the GPIIb IIIa complex (IgGL), or murine monoclonal antibodies specific for GPIb (AN51, 6D1), GPIIIa (AP-3), or GPIIb IIIa (AP-2) were studied using platelet suspension immunofluorescence tests. The binding of each antibody was quantified using a cytofluorograph (Ortho 50H). PLA1 and Leka antigens were expressed in normal amounts on fetal platelets as early as 16 weeks of intrauterine life. The GPIIb IIIa complex quantified by polyclonal or monoclonal antibodies was in the same range in fetuses (IgGL = 427 +/- 23 AUF, AP-2 = 459.5 +/- 8.5; AP-3 = 536 +/- 14) and in adults (IgGL = 420 +/- 30; AP-2 = 498 +/- 11; AP-3 = 515 +/- 13). The platelet binding of antibodies that recognized GPIb was higher in fetuses (AN51 = 491.5 +/- 14; 6D1 = 479 +/- 15) than in adults (AN51 = 426.5 +/- 9; 6D1 = 449 +/- 8.7). These results suggest that immunological techniques can be applied as early as 18 weeks of gestation for the antenatal diagnosis of GT and BSS.
29
Kunicki, TJ, R. Orchekowski, D. Annis, and Y. Honda. "Variability of integrin alpha 2 beta 1 activity on human platelets." Blood 82, no. 9 (November 1, 1993): 2693–703. http://dx.doi.org/10.1182/blood.v82.9.2693.2693.
Full textAbstract:
Abstract The activity and surface antigenicity of alpha 2 beta 1 on platelets from 27 normal subjects were found to vary significantly. A fourfold range of surface antigen correlates with a 20-fold variation in the ability of nonactivated, washed platelets to adhere to type I collagen and a fivefold variation in the adhesion of platelets to type III collagen. These differences in surface receptor are reflected in significant variation in the lag time required for type I collagen- induced platelet aggregation in platelet-rich plasma. Among the same individuals, no difference was observed in surface levels or activities of two other platelet integrins, the fibronectin receptor alpha 5 beta 1 and the fibrinogen receptor alpha IIb beta 3. In all cases studied, we observed complimentary differences in the incorporation of 125I into surface alpha 2 beta 1, in quantity of surface alpha 2 beta 1 antigens, and in alpha 2 beta 1 collagen receptor activity. Despite variations in these parameters, there was no difference in the electrophoretic mobility or isoelectric point of either integrin subunit among the individuals studied. The wide range of activity and antigenicity of this platelet collagen receptor may result from polymorphism(s) in the alpha 2 beta 1 genes, or the activity of alpha 2 beta 1 may be variably regulated by another gene product. The heterogeneity of platelet alpha 2 beta 1 that we describe in this report certainly explains previous discrepancies concerning the contributions of this integrin to platelet adhesion to collagens. Most importantly, differences in surface collagen receptor activity may correlate with a long-term risk toward thrombosis, impaired hemostasis, and/or cardiovascular disease.
30
Kunicki, TJ, R. Orchekowski, D. Annis, and Y. Honda. "Variability of integrin alpha 2 beta 1 activity on human platelets." Blood 82, no. 9 (November 1, 1993): 2693–703. http://dx.doi.org/10.1182/blood.v82.9.2693.bloodjournal8292693.
Full textAbstract:
The activity and surface antigenicity of alpha 2 beta 1 on platelets from 27 normal subjects were found to vary significantly. A fourfold range of surface antigen correlates with a 20-fold variation in the ability of nonactivated, washed platelets to adhere to type I collagen and a fivefold variation in the adhesion of platelets to type III collagen. These differences in surface receptor are reflected in significant variation in the lag time required for type I collagen- induced platelet aggregation in platelet-rich plasma. Among the same individuals, no difference was observed in surface levels or activities of two other platelet integrins, the fibronectin receptor alpha 5 beta 1 and the fibrinogen receptor alpha IIb beta 3. In all cases studied, we observed complimentary differences in the incorporation of 125I into surface alpha 2 beta 1, in quantity of surface alpha 2 beta 1 antigens, and in alpha 2 beta 1 collagen receptor activity. Despite variations in these parameters, there was no difference in the electrophoretic mobility or isoelectric point of either integrin subunit among the individuals studied. The wide range of activity and antigenicity of this platelet collagen receptor may result from polymorphism(s) in the alpha 2 beta 1 genes, or the activity of alpha 2 beta 1 may be variably regulated by another gene product. The heterogeneity of platelet alpha 2 beta 1 that we describe in this report certainly explains previous discrepancies concerning the contributions of this integrin to platelet adhesion to collagens. Most importantly, differences in surface collagen receptor activity may correlate with a long-term risk toward thrombosis, impaired hemostasis, and/or cardiovascular disease.
31
Bertrand, Gérald, Vincent Jallu, Maxime Gouet, Killie Mette Kjaer, Patrick Lambin, Anne Husebekk, and Cécile Kaplan. "Quantification of human platelet antigen-1a antibodies with the monoclonal antibody immobilization of platelet antigens procedure." Transfusion 45, no. 8 (June 10, 2005): 1319–23. http://dx.doi.org/10.1111/j.1537-2995.2005.00195.x.
Full text
32
Hutchinson, Tyler Davi d., Yuhua Song, Kevin Trainor, and Ghazala Hashmi. "Disequilibrium of Human Platelet Antigen 1 (HPA-1) in U.S. Population." Blood 112, no. 11 (November 16, 2008): 5466. http://dx.doi.org/10.1182/blood.v112.11.5466.5466.
Full textAbstract:
Abstract Background: Alloimmunization against Human Platelet Antigens (HPA) is associated with Neonatal Alloimmune Thrombocytopenia (NAIT), post-transfusion purpura and refractoriness for platelet transfusion. A flexible BeadChip™ design was developed to simultaneously detect 22 platelet antigens, including HPA-1, and used to assay over 1,000 random blood donors from across the United States. Methods: Samples from 19 labs/centers from across the country were assayed for 11 HPA loci (HPA-1 through 9, 11 and 15) using the BioArray Solutions HPA Assay. Each locus was independently assessed for Hardy-Weinberg Equilibrium. Results: Allele and genotype frequencies for each locus were reported. Platelet antigens HPA-2 through HPA-9, HPA-11 and HPA-15 were all found to be in Hardy-Weinberg Equilibrium with a Chi-Squared value of <3.84 (1 degree of freedom, 5% confidence interval). HPA-1, however, did not exhibit Hardy-Weinberg Equilibrium yielding a Chi-Squared value of 43.4. Conclusions: After reaffirming there was no sampling preference by inclusion of a second blinded random group, it was acknowledged that HPA-1 did not conform to a Mendelian distribution of alleles. The lower incidence of heterozygote HPA-1 individuals may lend credence to the recent finding by Ivanov et al (Akush Ginekol, 2007) linking the polymorphism in GPIIIa that is responsible for the HPA-1 antigen with embryo implantation failure. Further research may help elucidate the causes behind the HPA-1 disequilibrium and how much implantation failure impacts HPA-1 frequencies.
33
Choi, ES, JL Nichol, MM Hokom, AC Hornkohl, and P. Hunt. "Platelets generated in vitro from proplatelet-displaying human megakaryocytes are functional." Blood 85, no. 2 (January 15, 1995): 402–13. http://dx.doi.org/10.1182/blood.v85.2.402.bloodjournal852402.
Full textAbstract:
An in vitro culture system demonstrating the transitions from megakaryocyte progenitors to functional platelets is described. CD34- selected cells from normal human peripheral blood are cultured under conditions that promote megakaryocyte formation. After 8 to 11 days, enriched populations of mature megakaryocytes are replated under conditions that favor the development of proplatelets. Proplatelets express the platelet-specific proteins, glycoproteins Ib and IIb (GPIb and GPIIb), and fibrinogen and also contain microtubule coils equal in size to those found in plasma-derived platelets. In addition, proplatelets have ultrastructural features in common with plasma- derived platelets. Platelet-sized particles from the proplatelet culture supernatants are examined. Ultrastructurally, these particles are identical to plasma-derived platelets. Functionally, these culture- derived platelets aggregate in response to both thrombin and adenosine diphosphate (ADP) plus fibrinogen. This aggregation is specifically inhibited by the addition of a function-blocking anti-GPIIbIIIa antibody. Culture-derived platelets stimulated with agonists also express the activation-dependent antigens P-selectin and functional fibrinogen receptor. This is the first description of an in vitro culture system that sequentially demonstrates megakaryocyte growth, development, and platelet production.
34
Rock, Gail, and Maria Kolajova. "Proteomics Used To Identify the Target of a Platelet Aggregating Antibody in a Patient with HUS." Blood 104, no. 11 (November 16, 2004): 852. http://dx.doi.org/10.1182/blood.v104.11.852.852.
Full textAbstract:
Abstract Hemolytic Uremic Syndrome (HUS) has considerable overlap with Thrombotic Thrombocytopenia Purpura (TTP). Recently, evidence is emerging to suggest that TTP, like HIT, is an immune mediated disorder. We have investigated the plasmas of patients with Hemolytic Uremic Syndrome to determine the presence of antibodies and the specificity of the related antigens. Methods: A 20 year old female presented with repeated episodes of HUS. She is dialysis dependent. Plasma was taken for VWF, multimers, platelet aggregation, metalloprotease and inhibitor, western blot and 2D PAGE analysis. Results: At the time of the acute episodes, the VWF was increased three fold; the VWF multimer patterns on two occasions showed the presence of unusually large VWF forms. The metalloprotease was normal at all times and no inhibitor was present. Her platelets showed a normal response to aggregation, however, the plasma caused spontaneous aggregation of normal washed human platelets. This reactivity was removed after absorption with Staph A. On western blot analysis of platelet and microvascular endothelial cell lysate vs. patient plasma, multiple reactions were detected with a strong and persistent reactivity against antigens of 200,00 kDa and 55 kDa. Two dimensional PAGE of the whole platelet proteome identified strong immunoreactivity with two target spots in the 55 kDa area. Mass spectroscopy, using the nano-LC-MS/MS analysis, with the MASCOT search program confirmed the target antigen as beta fibrin with a molecular weight of 50.731 and an isoelectric point of 7.95 with a MASCOT score of 859 and 750 respectively. Conclusions: Anti-platelet antibodies which cross-react with platelet and microvascular endothelial cells are present in the plasma of patients with recurrent episodes of HUS. These antibodies cause aggregation of normal human platelets and are removed following specific absorption of IgG from the plasma. 2D proteomic analysis indicates that the antibody in our patient was directed against a specific antigen, B fibrin. The data suggests that HUS, like TTP and HIT has an immunological basis.
35
Gilson, Christopher R., Seema R. Patel, and James C. Zimring. "Co-Stimulatory Blockade Abrogates Alloimmunization to Transfused Platelets in a Mouse Model." Blood 118, no. 21 (November 18, 2011): 717. http://dx.doi.org/10.1182/blood.v118.21.717.717.
Full textAbstract:
Abstract Abstract 717 Background: Platelet transfusion therapy can be a life-sustaining treatment for patients with severe thrombocytopenia. However, alloimmunization is a potential sequelae of platelet transfusion with serious consequences for chronically transfused patients. Induction of alloantibodies, typically against HLA and/or human platelet antigens, can lead to poor survival of transfused platelets expressing the offending antigens. Patients with alloantibodies against multiple HLAs can become refractory to subsequent platelet therapy. Although leukoreduction of platelets has significantly decreased humoral alloimmunization rates, anti-HLA antibodies still form in a significant percentage of transfused patients. In addition to alloantibody formation, animal models have shown that platelet-induced T cell alloimmunity can contribute to the rejection of MHC identical bone marrow transplants across minor antigen barriers. Currently, there are no approved therapeutic interventions in humans to mitigate the risk of alloimmunization other than leukoreduction. Targeted blockade of T cell costimulation has shown great promise in inhibiting alloimmunity in the setting of solid organ transplantation; however, this strategy has not yet been explored in the context of platelet transfusion. Therefore, we tested the hypothesis that the costimulatory blockade reagent CTLA4-Ig, which interrupts the CD28-B7.1/2 T cell signaling pathway, would prevent alloreactivity against major and minor alloantigens on transfused platelets. Methods: C57BL/6 (H-2b) mice were transfused with filter leukoreduced platelets from BALB/c (H-2d) donors. Humoral alloimmunization was measured by indirect immunofluoresence using BALB/c splenocytes or platelets as targets, followed by flow cytometry. Platelet specific CD4+ T cell responses were analyzed by adoptive transfer of TCR75 CD4+ T cells (specific for a peptide from donor MHC I (Kd) presented by recipient MHCII (I-Ab)). Some transfusion recipients were subjected to a bone marrow transplant under reduced intensity conditioning (700 rads) using BALB.B mice as donors (MHC identical, minor antigen mismatched). Engraftment was studied by flow cytometry. Experimental animals received a 500 ug dose of CTLA-4 Ig or 500 ug of a control antibody. Results: The combined data from three separate experiments demonstrated that whereas 14/15 (93%) of control animals had anti-H2d antibodies after 4 weekly platelet transfusions, alloantibody formation was abrogated in all animals (n=15) given a single dose of CTLA4-Ig concurrent with the first platelet transfusion. This effect of CTLA4-Ig lasted at least 49 days after treatment. The proliferation of donor-specific CD4+ T cells was completely blocked by CTLA4-Ig, indicating an effect at the CD4+ T cell level. In addition, administration of a single dose of CTLA4-Ig prevented platelet transfusion induced BMT rejection. The combined results of three independent experiments demonstrated that while 14/15 (93%) of recipients transfused with BALB/c leukoreduced platelets rejected a bone marrow transplant in the presence of isotype control antibody, only 1/15 (7%) of CTLA4-Ig treated recipients rejected donor bone marrow. However, the timing of CTLA4-Ig administration was found to be critical. Delaying treatment until after platelet transfusion failed to prevent bone marrow transplant rejection. Conclusion: These findings demonstrate that costimulatory blockade in general, and CTLA4-Ig in particular, have the capacity to prevent both humoral and cellular alloimmunization to transfused platelets. These findings suggest costimulatory blockade may be a viable approach to decrease alloimmunization rates in humans receiving platelet transfusions. Disclosures: Zimring: Immucor Inc,: Research Funding. Off Label Use: We will describe use of CLTA4-Ig in an animal model for what would be an off label indication in humans. However, there are no human studies in this abstract.
36
Fischer, T. H., D. W. Barton, K. H. Krause, T. E. White, K. P. Campbell, and G. C. White. "The identification of sarcoplasmic reticulum terminal cisternae proteins in platelets." Biochemical Journal 263, no. 2 (October 15, 1989): 605–8. http://dx.doi.org/10.1042/bj2630605.
Full textAbstract:
Two new proteins with apparent molecular masses of 53 kDa and 190 kDa have been identified in both sarcoplasmic reticulum and human blood platelets using a monoclonal antibody, FII1b5. The sarcoplasmic reticulum FII1b5 antigens were present in the terminal cisternae fraction, but were absent from light sarcoplasmic reticulum. The platelet and skeletal muscle proteins were not sensitive to digestion with endoglycosidase H under conditions that removed carbohydrate from the 53 kDa glycoprotein in sarcoplasmic reticulum or GPIIIa in platelet microsomes and did not bind 45Ca in a nitrocellulose overlay calcium-binding assay. These results distinguished the FII1b5 antigens from the 53 kDa glycoprotein and calsequestrin of sarcoplasmic reticulum. The 190 kDa platelet and sarcoplasmic reticulum proteins were extracted from membranes with high concentrations of NaCl, indicating that the high molecular mass FII1b5 antigens are peripherally associated with the bilayers. In contrast, the platelet and muscle 53 kDa proteins remained membrane-bound in the presence of high salt concentrations, suggesting that they are integral proteins.
37
Bachelot, Christilla, Raphaël Saffroy, Sophie Gandrille, Martine Aiach, and Francine Rendu. "Role of FCγRIIA Gene Polymorphism in Human Platelet Activation by Monoclonal Antibodies." Thrombosis and Haemostasis 74, no. 06 (1995): 1557–63. http://dx.doi.org/10.1055/s-0038-1649982.
Full textAbstract:
SummaryThe aim of this study was to determine if there is a correlation between the activity of a MoAb as an agonist and its ability to bind to the Fc platelet receptor, FcγRIIa. A polymorphism at amino acid 131 [arginine (Arg) or histidine (His)] of FcγRIIa was first shown to be determinant for MoAb-IgG1 binding on monocytes. To clarify the role of this polymorphism in platelet activation by MoAb-IgG1 we (i) established the FCγRIIA polymorphism at the gene level by adapting the denaturating gradient gel electrophoresis method, (ii) analyzed the binding affinity of the MoAbs to FrγRIIa on platelets from homozygous Arg, homozygous His, and heterozygous Arg/His donors, and (iii) characterized the different reactivities of platelets according to the FCγRIIA polymorphism. Among 167 Caucasian donors we found 46% heterozygous Arg/His, 36% homozygous His and 18% homozygous Arg. ALB6, an anti CD9, P256 an anti GPIIb-IIIa, and AP3 an anti-GPIIIa were chosen according to their ability (ALB6, P256) or not (AP3) to activate platelets. These 3 MoAbs-IgG1 bind to FcγRIIa with a stronger affinity for the Arg-form of FcγRIIa, a result which was confirmed with the use of diverse MoAbs directed against various antigens. The different abilities of MoAbs to bind to the two FcγRIIa forms were well correlated to the different platelet responses induced by ALB6 and P256. However, low concentrations of ALB6, which allow full activation of platelets from homozygous Arg donors, as did P256, did not induce any activation of platelets from homozygous His donors, whereas P256 is able to induce a low aggregation. The results further define the respective roles of the antigen and the Fc receptor, depending on the MoAb, and the role of the FcγRIIa polymorphism in platelet activation induced by MoAbs. In addition, the results obtained with MoAbs unable to induce platelet activation provide evidence that the binding of a MoAb on FcγRIIa does not predict its ability to activate platelets.
38
Stenziger, Werner, Beate Kehrel, and Jürgen van de Loo. "Identification of Platelet Antigens by Immunoprecipitation of Unlabelled Platelet Glycoproteins." Thrombosis and Haemostasis 64, no. 03 (1990): 469–72. http://dx.doi.org/10.1055/s-0038-1647338.
Full textAbstract:
SummaryA time-saving and sensitive method for the identification of antigens on unlabelled platelet glycoproteins (GP) based on immunoprecipitation has been developed. Platelet solubilisates were incubated with antibodies to form GP-antibody complexes that were precipitated with Protein G Sepharose 4 Fast Flow (PGS). Pcs-bound material was eluted, separated by SDSPAGE under reducing conditions and visualized by silver staining. The method was designed as an alternative to radioimmunoprecipitation for laboratories not equipped to work with radioactive substances. It is proposed as a complementary procedure for the characterization of platelet GP antigens by murine monoclonal antibodies and human alloantibodies.
39
Choi, ES, JL Nichol, MM Hokom, AC Hornkohl, and P. Hunt. "Platelets generated in vitro from proplatelet-displaying human megakaryocytes are functional." Blood 85, no. 2 (January 15, 1995): 402–13. http://dx.doi.org/10.1182/blood.v85.2.402.402.
Full textAbstract:
Abstract An in vitro culture system demonstrating the transitions from megakaryocyte progenitors to functional platelets is described. CD34- selected cells from normal human peripheral blood are cultured under conditions that promote megakaryocyte formation. After 8 to 11 days, enriched populations of mature megakaryocytes are replated under conditions that favor the development of proplatelets. Proplatelets express the platelet-specific proteins, glycoproteins Ib and IIb (GPIb and GPIIb), and fibrinogen and also contain microtubule coils equal in size to those found in plasma-derived platelets. In addition, proplatelets have ultrastructural features in common with plasma- derived platelets. Platelet-sized particles from the proplatelet culture supernatants are examined. Ultrastructurally, these particles are identical to plasma-derived platelets. Functionally, these culture- derived platelets aggregate in response to both thrombin and adenosine diphosphate (ADP) plus fibrinogen. This aggregation is specifically inhibited by the addition of a function-blocking anti-GPIIbIIIa antibody. Culture-derived platelets stimulated with agonists also express the activation-dependent antigens P-selectin and functional fibrinogen receptor. This is the first description of an in vitro culture system that sequentially demonstrates megakaryocyte growth, development, and platelet production.
40
Chang, Y. W., J. Mytilineos, G. Opelz, and B. R. Hawkins. "Distribution of human platelet antigens in a Chinese population." Tissue Antigens 51, no. 4 (September 30, 2008): 391–93. http://dx.doi.org/10.1111/j.1399-0039.1998.tb02979.x.
Full text
41
Platt, Jeffrey L., and Zoie E. Holzknecht. "PORCINE PLATELET ANTIGENS RECOGNIZED BY HUMAN XENOREACTIVE NATURAL ANTIBODIES." Transplantation 57, no. 3 (February 1994): 327–35. http://dx.doi.org/10.1097/00007890-199402150-00003.
Full text
42
De La Vega Elena, C. D., N. Nogués, A. Fernández Montoya, S. Chialina, P. D. Blanzaco, E. Theiller, M. A. Raillon, et al. "Human platelet-specific antigens frequencies in the Argentinean population." Transfusion Medicine 18, no. 2 (April 2008): 83–90. http://dx.doi.org/10.1111/j.1365-3148.2007.00819.x.
Full text
43
Vazmitsel, Maryna, Dong Chen, Barbara Gruner, and Emily Coberly. "An Unusual Case of Fetal/Neonatal Alloimmune Thrombocytopenia." American Journal of Clinical Pathology 152, Supplement_1 (September 11, 2019): S151—S152. http://dx.doi.org/10.1093/ajcp/aqz131.002.
Full textAbstract:
Abstract Objectives Fetal/neonatal alloimmune thrombocytopenia (FNAIT) occurs when maternal IgG alloantibodies against paternal human platelet antigens (HPA) cross the placenta and cause the destruction of fetal platelets. The vast majority (up to 95%) of FNAIT cases are caused by antibodies against HPA-1a or HPA-5b antigens, while the remaining cases are usually due to antibodies against a variety of other HPA antigens. Cases of FNAIT due to anti-HLA antibodies are extremely uncommon and have only rarely been reported. We present a case of FNAIT suspected to be caused by anti-HLA class I alloantibodies. Methods The patient is a term infant boy born to a 32-year-old G2T2L2 mother. The mother had a previous diagnosis of Still disease (an adult form of systemic juvenile rheumatoid arthritis) but experienced complete resolution of symptoms and was off all treatment during the pregnancy. At birth, laboratory testing revealed isolated severe thrombocytopenia (platelet count 38,000/mcL) in an otherwise healthy-appearing infant. Results The infant had no evidence of bleeding, and testing for TORCH infection, sepsis, and DIC was negative. The maternal blood type was O positive. The maternal platelet count was normal. FNAIT was suspected and the infant was given two platelet transfusions from the same HPA 1a and 5b antigen-negative donor with no significant or sustained improvement in platelet count. Maternal platelet antibody testing subsequently revealed an absence of HPA antibodies, but anti-HLA class I alloantibodies were present. The infant was treated with three subsequent doses of IVIg with improvement in platelet count. No significant hemorrhage occurred. Conclusion HLA class I antibodies are commonly found in multiparous women but are not generally thought to cause significant fetal complications during subsequent pregnancies. This case suggests that, although rarely reported, HLA class I alloantibodies may be capable of causing FNAIT.
44
Rathore, Vipul, Matthew Meyers, and Bryan Ray. "PAKTM-Lx: A New Luminex*®-Based Assay to Detect and Identify Antibodies to Human Platelet Antigens (HPA) in Patient Serum." Blood 114, no. 22 (November 20, 2009): 4187. http://dx.doi.org/10.1182/blood.v114.22.4187.4187.
Full textAbstract:
Abstract Abstract 4187 Platelets express a variety of glycoproteins (GPIIb-IIIa, GPIa-IIa, GPIb/IX, GPIV, CD109 and Class I HLA). Human Platelet Antigens (HPA) represent polymorphisms of these platelet surface glycoproteins. While these polymorphisms do not alter the function of the proteins, they can become target of the immune system in mismatched individuals. Alloantibodies against HPA are involved in the pathogenesis of Neonatal Allo-Immune Thrombocytopenia (NAIT), Post-Transfusion Purpura (PTP) and refractoriness to random donor platelets. In addition to generating anti-HPA antibodies, these patients also develop antibodies to Class I Human Leukocyte Antigen (HLA). Most reference laboratories now use a combination of a sensitive screening assay such as the Platelet Immunofluorescence Test (PIFT) along with a solid phase assay for antibody identication, usually either the ELISA and Monoclonal Antibody Immobilization of Platelet Antigens (MAIPA) as well as genotyping techniques for at least HPAs 1, 2, 3, and 5. Currently, MAIPA is considered the gold standard in detection of antibodies to HPA. However, all existing methods have significant limitations in terms of sample requirements, time and labor involved. These factors are a major impediment as to how many specificities can be resolved in a rapid, efficient and reproducible manner. Development of microbead-based assays like the xMAP (Luminex®) has provided a technology that can resolve these questions. GTI Diagnostics® and Gen-Probe have developed PAKTM -Lx, a bead-based assay for the Luminex® platform to detect and determine the specificity of anti-HPA antibodies. PAKTM -Lx is capable of resolving the specificities of antibodies to HPA 1, 2, 3, 4 and 5 in addition to detecting antibodies against GPIV and HLA Class-I antigens. Furthermore, it is capable of detecting antibodies to multiple HPA and HLA with only 10 μl of sample. With a total time of less than two hours from addition of samples to end results, PAKTM -Lx is sensitive, rapid and simple to perform. Focused, flexible multiplexing in the range of 1 to 100 analytes provided by Luminex® technology meets the needs to expand the panel to include more HPA combinations, thereby reducing sample requirements, labor and costs. Disclosures: No relevant conflicts of interest to declare.
45
Lin, Xin, Ermelina Enriquez, Jigar Patel, Ruth Huang, Cindi Marks, Sunitha Vege, KL Billingsley, Joann M. Moulds, and Ghazala Hashmi. "Universal DNA Arrays for High-Throughput SNP Detection of Human Platelet Antigens (HPA)." Blood 116, no. 21 (November 19, 2010): 4403. http://dx.doi.org/10.1182/blood.v116.21.4403.4403.
Full textAbstract:
Abstract Abstract 4403 Background: DNA analysis of human platelet antigens is known to improve the diagnosis and treatment of neonatal alloimmune thrombocytopenia and minimize the risks of post transfusion purpura and refractoriness to random donor platelet therapy. The availability of reliable molecular platforms such as HPA eMAP assays analyzing HPA-1, -2, -3, -4, -5, -6, -7, -8, -9, -11, and -15, are routinely used and eliminate the need for reference sera or large platelet volumes. New generations of HPA assays (HPA eMAP-S Beadchip™ Kit) described here are developed by identification of specific allele in solution and detection of targets by a generic probe array called the Universal BeadChip™ by imaging, HPA-13 was also incorporated in the panel. These assays are easily automatable due to fewer protocol steps. Methods: The BioArray Solutions HPA eMAP-S BeadChip Kit uses the novel Elongation Mediated Multiplexed Analysis of Polymorphisms in Solution (eMAP-S) technology (Lin, X., et al., 2010) to identify the presence or absence of the selected alleles associated with a given phenotype. We amplified 10 DNA fragments covering 12 allele variants which are associated with 12 platelet antigens by using multiplex PCR and HPA gene specific primer pairs. PCR was followed by multiplex allele specific primer extension (ASPE) and Beadchip detection by using the AIS-400 Array Imaging System. To evaluate the overall performance of HPA eMAP-S BeadChip™ Kits, a total 552 clinical samples with known HPA eMAP phenotype and/or serology were analyzed to determine polymorphisms associated with common human platelet antigen (HPA-1, -2, -3, -5, -15) and less common human platelet antigen (HPA-4, -6, -7, -8, -9, -11, -13). For internal study, 176 clinical samples were analyzed at BioArray Solutions (BAS). For the external study, 186 and 190 (total 376) donor samples were tested at two sites and analyzed by BASIS™ software. Phenotype results obtained from the HPA eMAP-S Beadchip™ Kit during the studies were compared to the data generated from the HPA eMAP BeadChip™ Kit and/or serology. Results: For internal and external studies, the concordance between the HPA eMAP-S Beadchip™ kit and HPA eMAP Beadchip™ kit was 99.99%. The discordant call (0.01%) on HPA-1b antigen was investigated. One HPA-1 discordant sample was sent out for sequencing and re-analyzed by using increased amount of DNA from DNA precipitation. The result from sequencing is consistent with the result from HPA eMAP Beadchip™ Kit. The HPA eMAP-S result from higher concentration DNA is also consistent with the result of sequencing. The discordance in the original HPA eMAP-S assay was attributed to less DNA input in the multiplex PCR, which will be corrected in the Package Insert of HPA eMAP-S Beadchip™ Kit. Conclusion: HPA eMAP-S Beadchip™ Kit could be used reliably for the determination of human platelet antigens using DNA analysis. Disclosures: Hashmi: Immucor: Employment.
46
Simsek, S., NM Faber, PM Bleeker, AB Vlekke, E. Huiskes, R. Goldschmeding, and AE von dem Borne. "Determination of human platelet antigen frequencies in the Dutch population by immunophenotyping and DNA (allele-specific restriction enzyme) analysis." Blood 81, no. 3 (February 1, 1993): 835–40. http://dx.doi.org/10.1182/blood.v81.3.835.835.
Full textAbstract:
Abstract Platelets from 200 random Dutch blood donors were typed for the human platelet alloantigens HPA-1 to -5 recognized at present and for Naka. Naka is an epitope on glycoprotein IV, not expressed on the platelet of individuals with hereditary GP IV deficiency. Platelet immunofluorescence and monoclonal antibody-specific immobilization of platelet antigens (MAIPA) were applied for this purpose. The observed phenotype frequencies were 97.86% and 28.64% for HPA-1a and -1b, 100% and 13.15% for HPA-2a and -2b, 80.95% and 69.84% for HPA-3a and -3b, 100% and 0% for HPA-4a and -4b, 100% and 19.7% for HPA-5a and HPA-5b, respectively. Platelets from all donors reacted with the anti-Naka antibodies. To determine the gene frequencies for the HPA-1, HPA-2 and HPA-3 systems directly, DNA from 98 of these donors was isolated from peripheral blood mononuclear leucocytes and specific fragments were amplified by polymerase chain reaction (PCR). The fragments were analyzed using allele-specific restriction enzymes (ASRA). In all amplified PCR products an “internal control” for each assay, ie, a restriction site for the applied enzyme independent from the phenotype of the donor was present. In all donors tested, phenotypes, as determined by serological methods and genotypes, directly determined by the ASRA, were identical. Thus, the PCR-ASRA described in this report is a practical and reliable technique for the determination of alleles that code for platelet antigen allotypes, at least in the Dutch population.
47
Simsek, S., NM Faber, PM Bleeker, AB Vlekke, E. Huiskes, R. Goldschmeding, and AE von dem Borne. "Determination of human platelet antigen frequencies in the Dutch population by immunophenotyping and DNA (allele-specific restriction enzyme) analysis." Blood 81, no. 3 (February 1, 1993): 835–40. http://dx.doi.org/10.1182/blood.v81.3.835.bloodjournal813835.
Full textAbstract:
Platelets from 200 random Dutch blood donors were typed for the human platelet alloantigens HPA-1 to -5 recognized at present and for Naka. Naka is an epitope on glycoprotein IV, not expressed on the platelet of individuals with hereditary GP IV deficiency. Platelet immunofluorescence and monoclonal antibody-specific immobilization of platelet antigens (MAIPA) were applied for this purpose. The observed phenotype frequencies were 97.86% and 28.64% for HPA-1a and -1b, 100% and 13.15% for HPA-2a and -2b, 80.95% and 69.84% for HPA-3a and -3b, 100% and 0% for HPA-4a and -4b, 100% and 19.7% for HPA-5a and HPA-5b, respectively. Platelets from all donors reacted with the anti-Naka antibodies. To determine the gene frequencies for the HPA-1, HPA-2 and HPA-3 systems directly, DNA from 98 of these donors was isolated from peripheral blood mononuclear leucocytes and specific fragments were amplified by polymerase chain reaction (PCR). The fragments were analyzed using allele-specific restriction enzymes (ASRA). In all amplified PCR products an “internal control” for each assay, ie, a restriction site for the applied enzyme independent from the phenotype of the donor was present. In all donors tested, phenotypes, as determined by serological methods and genotypes, directly determined by the ASRA, were identical. Thus, the PCR-ASRA described in this report is a practical and reliable technique for the determination of alleles that code for platelet antigen allotypes, at least in the Dutch population.
48
Roz̆man, Primoz̆. "Platelet antigens. The role of human platelet alloantigens (HPA) in blood transfusion and transplantation." Transplant Immunology 10, no. 2-3 (August 2002): 165–81. http://dx.doi.org/10.1016/s0966-3274(02)00063-1.
Full text
49
Vassallo, Ralph R. "Recognition and management of antibodies to human platelet antigens in platelet transfusion-refractory patients." Immunohematology 25, no. 3 (2020): 119–24. http://dx.doi.org/10.21307/immunohematology-2019-244.
Full text
50
Franceschi, F., R. M. Genta, A. Gasbarrini, E. C. Nista, A. R. Sepulveda, R. De Cristofaro, R. Tartaglione, et al. "Cross-reactivity between anti-CagA antibodies and human platelet antigens." Digestive and Liver Disease 32 (November 2000): A85. http://dx.doi.org/10.1016/s1590-8658(00)80517-4.
Full text