A New Private Platelet Antigen, Gro^a, Localized on Glycoprotein IIIa, Involved in Neonatal Alloimmune Thrombocytopenia

Vox Sanguinis ◽  
1994 ◽  
Vol 67 (3) ◽  
pp. 302-306 ◽  
Author(s):  
Suat Simsek ◽  
André B.J. Vlekke ◽  
Robert W.A.M. Kuijpers ◽  
Roel Goldschmeding ◽  
Albert E.G.Kr. von dem Borne
Blood ◽  
1990 ◽  
Vol 76 (11) ◽  
pp. 2296-2302 ◽  
Author(s):  
H Kroll ◽  
V Kiefel ◽  
S Santoso ◽  
C Mueller-Eckhardt

Abstract A new platelet alloantigen, Sra, is described that was defined by an alloantibody detected in the serum of a healthy mother who delivered a child with typical clinical signs of neonatal alloimmune thrombocytopenia (NAIT). The antibody reacted strongly with the child's and father's platelets, but not with platelets of the mother or with those of a highly selected panel representing all known platelet alloantigens. Platelets from 300 unselected normal blood donors also tested negative, suggesting a phenotype frequency in the German population of less than 0.01. The antigen was present in 9 of 20 members within three generations of the paternal family, indicating autosomal codominant inheritance. By immunochemical analysis using a glycoprotein (GP)-specific immunoassay and a variety of GP IIb/IIIa- specific monoclonal antibodies for antigen immobilization (MAIPA assay), radioimmunoassay, and Western blotting, we could show that the antigen resides on a 68-Kd proteolytic fragment of GP IIIa. Immunogenetic data and gene dosage studies revealed that the Sra antigen is not related to any of the other known platelet alloantigens. In accordance with established criteria, the Sra antigen represents the first example of a “private” platelet alloantigen that bears significance in rare instances of NAIT.


Vox Sanguinis ◽  
1994 ◽  
Vol 67 (3) ◽  
pp. 302-306 ◽  
Author(s):  
Suat Simsek ◽  
André B.J. Vlekke ◽  
Robert W.A.M. Kuijpers ◽  
Roel Goldschmeding ◽  
Albert E. G. Kr. Borne

Blood ◽  
1990 ◽  
Vol 76 (11) ◽  
pp. 2296-2302
Author(s):  
H Kroll ◽  
V Kiefel ◽  
S Santoso ◽  
C Mueller-Eckhardt

A new platelet alloantigen, Sra, is described that was defined by an alloantibody detected in the serum of a healthy mother who delivered a child with typical clinical signs of neonatal alloimmune thrombocytopenia (NAIT). The antibody reacted strongly with the child's and father's platelets, but not with platelets of the mother or with those of a highly selected panel representing all known platelet alloantigens. Platelets from 300 unselected normal blood donors also tested negative, suggesting a phenotype frequency in the German population of less than 0.01. The antigen was present in 9 of 20 members within three generations of the paternal family, indicating autosomal codominant inheritance. By immunochemical analysis using a glycoprotein (GP)-specific immunoassay and a variety of GP IIb/IIIa- specific monoclonal antibodies for antigen immobilization (MAIPA assay), radioimmunoassay, and Western blotting, we could show that the antigen resides on a 68-Kd proteolytic fragment of GP IIIa. Immunogenetic data and gene dosage studies revealed that the Sra antigen is not related to any of the other known platelet alloantigens. In accordance with established criteria, the Sra antigen represents the first example of a “private” platelet alloantigen that bears significance in rare instances of NAIT.


Blood ◽  
2006 ◽  
Vol 107 (7) ◽  
pp. 2976-2983 ◽  
Author(s):  
Heyu Ni ◽  
Pingguo Chen ◽  
Christopher M. Spring ◽  
Ebrahim Sayeh ◽  
John W. Semple ◽  
...  

AbstractFetal and neonatal alloimmune thrombo cytopenia (FNAITP) is a life-threatening bleeding disorder caused by maternal antibodies directed against fetal platelet antigens. The immunoreactive epitopes in FNAITP are primarily located in the extracellular regions of the platelet glycoprotein IIIa (β3 integrin). Here we have established a novel animal model of FNAITP using β3 integrin–deficient (β3-/-) mice. We demonstrated first that these mice are immunoresponsive to β3 integrin; β3-/- mice transfused with wild-type platelets generated specific anti–β3 antibodies which were able to induce thrombocytopenia in wild-type mice. Subsequently, β3-/- female mice (both naive and immunized) were bred with wild-type male mice to recapitulate the features of FNAITP. The titer of generated maternal antibodies correlated with the severity of FNAITP. High titer maternal anti–β3 anti-bodies caused severe fetal thrombocytopenia, intracranial hemorrhage, and even miscarriage. Furthermore, maternal administration of intravenous immunoglobulin G (IgG) ameliorated FNAITP and down-regulated pathogenic antibodies in both the maternal and fetal circulations.


Transfusion ◽  
2014 ◽  
Vol 55 (6pt2) ◽  
pp. 1584-1585 ◽  
Author(s):  
Mia J. Sullivan ◽  
Julie Peterson ◽  
Janice G. McFarland ◽  
Daniel Bougie ◽  
Richard H. Aster ◽  
...  

Author(s):  
Lisa Rockenbauer ◽  
Beate Eichelberger ◽  
Simon Panzer

AbstractThe identification of platelet alloantibodies is indispensible for the diagnoses of fetal/neonatal alloimmune thrombocytopenia and refractoriness to platelet transfusions.We compared the results obtained with the gold-standard assay for the detection and specification of platelet antibodies, the monoclonal antibody-specific immobilization of platelet antigen assay (MAIPA), with those from two bead-based assays, simultaneous analysis of specific platelet antibodies assay (SASPA), and the recently commercialized bead-based assay Pak Lx.For the detection of alloantibodies by SASPA, the sensitivity was 94.6%, the specificity was 99.5% The respective results for Pak Lx were 98% and 99.8%. Some antibody specificities were revealed by SASPA or Pak Lx but not by MAIPA. However, there were also antibodies detected by MAIPA that were not seen by SASPA or Pak Lx. Antibody dilution experiments suggest that SASPA or Pak Lx are more sensitive than MAIPA.All three assays have limitations, but Pak Lx is suited for screening. However, other assays are necessary if results are not conclusive or for evaluations beyond the commercial assay’s design.


Vox Sanguinis ◽  
1986 ◽  
Vol 50 (3) ◽  
pp. 177-180 ◽  
Author(s):  
Yoichi Shibata ◽  
Isao Matsuda ◽  
Toru Miyaji ◽  
Yoichi Ichikawa

Transfusion ◽  
2009 ◽  
Vol 49 (5) ◽  
pp. 953-958 ◽  
Author(s):  
Alina G. Lemnrau ◽  
Sandra Cardoso ◽  
Lisa E. Creary ◽  
Colin Brown ◽  
Marcos Miretti ◽  
...  

Blood ◽  
1993 ◽  
Vol 81 (1) ◽  
pp. 70-76 ◽  
Author(s):  
RW Kuijpers ◽  
S Simsek ◽  
NM Faber ◽  
R Goldschmeding ◽  
RK van Wermerkerken ◽  
...  

Abstract Here we describe a new platelet-specific alloantigen that was identified in a case of neonatal alloimmune thrombocytopenia. This antigen has provisionally been called “Mo.” By studying the Mo family, it was shown to be inherited in an autosomal dominant manner. Immunoprecipitation and Western blot analysis showed that the antigen resides on platelet glycoprotein IIIa (GP IIIa). Genomic analysis, performed by applying polymerase chain reaction and sequencing, showed a C-->G substitution of base pair 1267 of the coding region of the DNA for GP IIIa, resulting in a substitution of Proline407 by Alanine407. That this substitution is associated with the antigen could be demonstrated by restriction fragment length polymorphism analysis of cDNA, prepared from platelet RNA, and of genomic DNA. It was confirmed by dot-blot hybridization with allele-specific oligonucleotides. All family members, also those being Mo antigen-positive, were healthy. None of them appeared to suffer from increased tendency of bleeding or thrombosis. Thus, the Mo mutation does not lead to significant platelet dysfunction in vivo with heterozygous carriers. One of 450 random healthy blood donors who were tested was positive for the Mo antigen. Typing was performed by the classical serologic methods as well as by DNA analysis.


Transfusion ◽  
2010 ◽  
Vol 50 (6) ◽  
pp. 1276-1284 ◽  
Author(s):  
Yangsook Koh ◽  
Atsuko Taniue ◽  
Hiroyuki Ishii ◽  
Nobuki Matsuyama ◽  
Etsuko Amakishi ◽  
...  

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