Volume 51, Issue 8 pp. 1745-1754

A new platelet alloantigen, Swia, located on glycoprotein Ia identified in a family with fetal and neonatal alloimmune thrombocytopenia

Hartmut Kroll

Corresponding Author

Hartmut Kroll

Hartmut Kroll, MD, Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, 06847 Dessau, Germany; e-mail: [email protected]. Search for more papers by this author
Korinna Feldmann

Korinna Feldmann

From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.

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Claudia Zwingel

Claudia Zwingel

From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.

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Jochen Hoch

Jochen Hoch

From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.

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Rainer Bald

Rainer Bald

From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.

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Gregor Bein

Gregor Bein

From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.

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Behnaz Bayat

Behnaz Bayat

From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.

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Sentot Santoso

Sentot Santoso

From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.

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First published: 18 February 2011
Citations: 11

Abstract

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by transplacental passage of maternal antibodies to fetuses whose platelets (PLTs) express the corresponding human PLT antigen (HPA).

STUDY DESIGNS AND METHODS: We observed a fetus with FNAIT who died from a severe intracranial hemorrhage. Analysis of maternal serum in antigen capture assay with paternal PLTs showed reactivity with PLT glycoprotein (GP)IIb/IIIa (αIIbβ3) and GPIa/IIa (α2β1 integrin), indicating the presence of anti-HPA-1a and an additional alloantibody against GPIa (termed anti-Swia).

RESULTS: By immunochemical studies, the localization of the Swia antigen on GPIa/IIa could be confirmed. Analysis of paternal GPIa full-length cDNA showed a single-nucleotide substitution C3347T in Exon 28 resulting in a Thr1087Met amino acid substitution. Testing of family members by polymerase chain reaction-restriction fragment length polymorphism using MslI endonuclease showed perfect correlation with phenotyping. Extended family and population studies showed that 4 of 10 members of the paternal family but none of 500 unrelated blood donors were Swia carriers. Expression studies on allele-specific transfected Chinese hamster ovary (CHO) cells confirmed that the single-amino-acid substitution Thr1087Met was responsible for the formation of the Swia epitope. Adhesion of CHO cells expressing the Swia alloantigen to immobilized collagens was not impaired compared to the wild-type control and was not inhibited by anti-Swia alloantibodies.

CONCLUSION: In this study we defined a new PLT alloantigen Swia that was involved in a case of additional immunization against HPA-1a. Our observations demonstrate that combinations of PLT-specific alloantibodies may comprise low-frequency alloantigens.

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