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- Title
Alloantibody against new platelet alloantigen (Lap(a)) on glycoprotein IIb is responsible for a case of fetal and neonatal alloimmune thrombocytopenia.
- Authors
Wihadmadyatami, Hevi; Heidinger, Kathrin; Röder, Lida; Werth, Silke; Giptner, Astrid; Hackstein, Holger; Knorr, Martin; Bein, Gregor; Sachs, Ulrich J.; Santoso, Sentot
- Abstract
<bold>Background: </bold>Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by the destruction of platelets (PLTs) in the fetus or newborn by maternal PLT antibodies that crossed the placenta during pregnancy.<bold>Study Design and Methods: </bold>In this study, we aim to elucidate the properties of a new PLT alloantigen (Lap(a)) that is associated with a severe case of FNAIT. Analysis of maternal serum with phenotyped PLTs by monoclonal antibody-specific immobilization of platelet antigens showed positive reaction against PLT glycoprotein (GP)IIb/IIIa and HLA Class I expressed on paternal PLTs.<bold>Results: </bold>In contrast to GPIIIa-reactive anti-HPA-1a, anti-Lap(a) alloantibodies precipitated predominantly GPIIb. Indeed, a point mutation G>C at Position 2511 located in Exon 25 of the ITGA2B gene was found in Lap(a)-positive donors. This mutation causes an amino exchange Gln>His at Position 806 located in the calf-2 domain of GPIIb. Lap(a)-positive individuals were not found in 300 random blood donors. Our expression study showed that anti-Lap(a) alloantibodies reacted with stable transfected HEK293 cells expressing the mutated GPIIb isoform (His806). CHO cells carrying this isoform, however, failed to react with anti-Lap(a) alloantibodies, indicating that Lap(a) epitopes depend on the Gln806 His mutation and the carbohydrate composition of the GPIIb. This mutation did not hamper the binding of anti-HPA-3a, which recognizes a point mutation (Ile843 Ser) located in calf-2 domain. Finally, we found that Lap(a) and some HPA-3a epitopes are sensitive to O-glycanase.<bold>Conclusions: </bold>This study not only underlines the relevance of rare HPAs on the pathomechanism of FNAIT, but also helps to understand the pitfalls of serologic assays to detect anti-GPIIb alloantibodies.
- Subjects
THROMBOCYTOPENIA in children; MONOCLONAL antibodies; BLOOD platelets; PLACENTA; ANTIGENS; GLYCOPROTEINS; ANIMALS; EPITHELIAL cells; IMMUNOGLOBULINS; ISOANTIGENS; RODENTS; THROMBOCYTOPENIA
- Publication
Transfusion, 2015, Vol 55, Issue 12, p2920
- ISSN
0041-1132
- Publication type
journal article
- DOI
10.1111/trf.13238