Platelet specific alloantigens on the platelet glycoprotein Ia/IIa complex (original) (raw)
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Genomic RFLP typing of human platelet alloantigens Zw(PlA), Ko, Bak and Br (HPA-1, 2, 3, 5)
British Journal of Haematology, 1995
The diallelic human platelet alloantigen systems 1-5 have been found to result from single base pair substitutions in the encoding genes of platelet membrane glymproteins IIIa, Ib, IIb and Ia. This is the basis of DNA methods for determination of platelet alloantigens. In this study, 98 blood donors were typed in the HPA-1, 2, 3 systems and, for the fist t i e , in the HPA-5 system. Serologically obtained data (MAIPA and platelet agglutination) were compared with results from analysis of restriction fragment length polymorphisms (RFLP). Discordances were found in the HPA-2 and 3 systems and can be ascribed to false typing results in both the serological and genomic methods. In the HPA-1, 2 and 5 systems, all samples were typed correctly with RFLP analysis. Serologically, two donors were falsely typed positive with anti-HPA-2b in platelet agglutination and one donor with anti-HPA-3a in MAIPA assay. In the HPA-3 system, another four donors were misinterpreted to be HPA-3a negative in RFLP analysis. Possible technical problems in PCR-RFLP-typing are discussed and another strategy of HPA-1 typing using the restriction enzyme Scr FI is evaluated.
Identification of the Yukb Allo‐Antigen on Platelet Glycoprotein IIIa
Vox Sanguinis, 1987
The glycoprotein (GP) localization of a new platelet-specific allo-antigen Yukb is described. The antibody was isolated from serum of a patient with neonatal allo-immune thrombocytopenia. In immunoblot procedure, it bound exclusively to platelet GP IIIa, like anti-PIA1, while the known anti-Baka and anti-Leka reacted with GP IIb. Analysis of GP from chymotrypsin-treated platelets with anti-Yukb revealed no binding in the 68-kilodalton position while anti-PIA1 did. Thus, unlike the PIA1 antigen, the Yukb determinant either resides on the 30-kilodalton fragment of GP IIIa or it is destroyed by chymotrypsin treatment.
Blood group A and B antigens are strongly expressed on platelets of some individuals
Blood, 2000
It is widely thought that expression of ABH antigens on platelets is insufficient to materially affect the survival of ABH-incompatible platelets in transfusion recipients, but anecdotal reports of poor survival of A and B mismatched platelets suggest that this is not always the case. The A and B antigen expression on platelets of 100 group A(1) and group B blood donors was measured, and 7% and 4%, respectively, had platelets whose A and B antigen levels consistently exceeded the mean plus 2 SD. On the basis of flow cytometric and statistical analysis, donors whose platelets contained higher than normal levels of A antigen were subdivided into 2 groups, designated Type I and Type II ("high expressers"). Serum A(1)- and B-glycosyltransferase levels of A and B high expressers were significantly higher than those of group A(1) and B individuals with normal expression. H antigen levels were low on the red cells of high expressers, indicating that the anomaly affects other cell...
Journal of Clinical Investigation, 1987
Neonatal alloimmune thrombocytopenic purpura associated with a new platelet-specific alloantigen Pen' has been reported. We now provide direct evidence that the Pen' determinant is associated with glycoprotein (GP) IIIa, but that it is distinct from epitopes that define the pIA system. By ELISA wherein monoclonal antibodies specific for GPIIb (Tab) and specific for GPIIIa (AP3) were used to capture and hold antigens from a platelet lysate prepared under conditions that generate free GPIIb and GPIIIa, anti-Pen' reacted with GPIIIa held by AP3 but not with GPIIb held by Tab. In an alternative ELISA where purified GPIIIa from both PlAl-positive and PlAl-negative platelets were used individually as antigen, anti-Pen' reacted with both allelic forms of GPIIIa. By radioimmunoprecipitation, anti-Pen' precipitated a single surface-labeled membrane protein with electrophoretic characteristics in sodium dodecyl sulfate-polyacrylamide gels, under nonreduced or reduced conditions, identical to those of GPIIIa. By fluorocytometry, platelets from several donors, regardless of peA phenotype, bound an amount of anti-Pen' roughly equivalent to one-half that amount of anti-PlI' bound by PeAl homozygous (Al/Al) platelets and roughly equal to that amount of anti-P1Ae bound by p1Al heterozygous (Al/A2) platelets. Using platelets from donors typed homozygous for p1Al and Pen' in a quantitative indirect binding assay, 14-24,000 molecules of anti-Pen' and 41-51,000 molecules of anti-PlAl were bound per platelet at saturation. Anti-Pen' completely inhibited ADP-induced aggregation of Pen3-positive platelets, regardless of peA phenotype. These results indicate that the Pen' determinant is associated with GPIIIa but distinct from PA.
Scandinavian Journal of Immunology, 1977
Antibodies directed against specific human la-type antigens can easily be detected and quantitated by an improved radioimmunoassay using iodinated protein A bound to a specific antibody-Ia-antigen complex on the surface of freshly drawn peripheral human leukocytes, cultured human cell lines, or lymphoid cells fixed with glutardialdehyde or formaldehyde. The same principle can also be used for the detection of la alloantigens on human lymphocytes when testing them with specific antisera known to contain antibodies against transplantation antigens. These anti-Ia-alloantigen antibodies had been purified by a two-step procedure involving ion-exchange chromatography on DEAE-cellulose at pH 6.3 and the specific absorption on formaldehyde-fixed Ia-alloantigen-carrying homozygous cell lines, foiiowed by elution of these antibodies with isotonic citrate buffer at pH 3.0. In this way an about 90-fold purification could be achieved. After such a purification the highly enriched antibody fraction still reacted selectively with one specificity of the la antigen system.
British Journal of Haematology, 2000
The glycosylphosphatidylinositol-linked platelet protein CD109 carries the biallelic alloantigen system Gov. There is limited information on the incidence of Gov alloantibodies in neonatal alloimmune thrombocytopenia (NAITP), post-transfusion purpura (PTP) and platelet refractoriness. We adapted the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay to the detection of Gov antibodies and determined their incidence in 605 archived samples (112 with HPA antibodies) referred for the aforementioned conditions. Here, we show that CD109 expression was reduced upon platelet storage in saline or by cryopreservation, but was stable when stored as whole blood or therapeutic platelet concentrate. Fourteen of the 605 samples contained Gov alloantibodies (anti-Gov a , n 10; anti-Gov b , n 4), with the majority in platelet refractoriness (n 9) and, of the remaining five, four in NAITP and one in PTP. In seven cases, no other HPA antibodies were detected, three being NAITP cases. The incidence of Gov antibodies was significantly lower than HPA-1 system antibodies (n 87), but equalled the number of HPA-5 system antibodies (n 14) and outnumbered HPA-2 and -3 system antibodies (10 altogether).
Transfusion Medicine, 2010
Objective/Aim: The aim of this study is to describe the distribution of the platelet blood group A antigenicity in Euro-Brazilians (EUBs) and Afro-Brazilians (AFBs). Background: A small but significant proportion of individuals express high levels of A or B antigen on their platelets corresponding to the erythrocyte ABO group. The mechanism of increased antigen expression has not been elucidated. Material/Methods: A cohort of 241 blood group A donors was analysed by flow cytometry. Although mean fluorescence intensity (MFI) is a typical continuous variable, platelets were screened and divided into two categories: low expressers (LEs) and high expressers (HEs). A three-generation family was investigated looking for an inheritance mechanism. Results: The prevalence of the HE platelet phenotype among group A 1 donors was 2%. The mean of MFI on platelets of A 1 subgroup of EUBs differs from that of AFBs (P = 0·0115), whereas the frequency of the HE phenotype was similar between them (P = 0·5251). A significant difference was found between sexes (P = 0·0039). Whereas the serum glycosyltransferase from HE family members converted significantly more H antigen on group O erythrocytes into A antigens compared with that in LE serum, their ABO, FUT1 and FUT2 genes were consensus. The theoretically favourable, transcriptionally four-repeat ABO enhancer was not observed. Conclusion: The occurrence of HE in several members suggests familial aggregation. Indeed, in repeated measures, stability of the MFI values is suggesting an inherited condition. Factors outside the ABO locus might be responsible for the HE phenotype. Whether the real mechanism of inheritance is either of a polygenic or of a discrete Mendelian nature remains to be elucidated.
HPA-1a/b (PlA1/A2, Zwa/b): the odyssey of an alloantigen system
Immunohematology, 2020
The HPA-1a/b (Pl A1/A2 , Zw a/b) alloantigen system was one of the first such systems to be identified on a cell other than the RBC. From the discovery of HPA-1a in 1958 to the present day, studies of this antigen and its allele, HPA-1b, have led to a remarkable number of "firsts" in immunobiology. In this review, we shall trace the history of the HPA-1a/b system and will highlight selected observations made during the past 48 years that have contributed not only to the field of platelet immunology but also to immunohematology and transfusion medicine in general.