Journal article

Publication year: 2015

Pages: 2920-2929

Journal: Transfusion

Volume number: 55

Issue number: 12

ISSN: 0041-1132

eISSN: 1537-2995

DOI Link: https://doi.org/10.1111/trf.13238

Publisher: Wiley

Abstract: 

BACKGROUND: 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.

STUDY DESIGN AND METHODS: 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.

RESULTS: 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 Gln(806)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 (Ile(843)Ser) located in calf-2 domain. Finally, we found that Lap(a) and some HPA-3a epitopes are sensitive to O-glycanase.

CONCLUSIONS: 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.

Harvard Citation style: Wihadmadyatami, H., Heidinger, K., Roeder, L., Werth, S., Giptner, A., Hackstein, H., et al. (2015) Alloantibody against new platelet alloantigen (Lap^a) on glycoprotein IIb is responsible for a case of fetal and neonatal alloimmune thrombocytopenia, Transfusion, 55(12), pp. 2920-2929. https://doi.org/10.1111/trf.13238

APA Citation style: Wihadmadyatami, H., Heidinger, K., Roeder, L., Werth, S., Giptner, A., Hackstein, H., Knorr, M., Bein, G., Sachs, U., & Santoso, S. (2015). Alloantibody against new platelet alloantigen (Lap^a) on glycoprotein IIb is responsible for a case of fetal and neonatal alloimmune thrombocytopenia. Transfusion. 55(12), 2920-2929. https://doi.org/10.1111/trf.13238