title: Alloantibody against new platelet alloantigen (Lap(a)) on glycoprotein IIb is responsible for a case of fetal and neonatal alloimmune thrombocytopenia.
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.
  
  
  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 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.
  
  
  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.
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.|Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia.
authors.forename: Hevi
authors.initials: H
authors.lastname: Wihadmadyatami
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Heidinger
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
authors.forename: Lida
authors.initials: L
authors.lastname: Röder
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Werth
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Giptner
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Hackstein
authors.affiliation: Department of Paediatric Oncology and Haematology, University Clinic, Essen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Knorr
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Bein
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
authors.forename: Ulrich J
authors.initials: UJ
authors.lastname: Sachs
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
authors.forename: Sentot
authors.initials: S
authors.lastname: Santoso
mesh_terms: D000818:Animals; D016824:Antigens, Human Platelet / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology*; D016466:CHO Cells; D002675:Child, Preschool; D003412:Cricetulus; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D007519:Isoantigens / Q000276:immunology*; D040201:Platelet Membrane Glycoprotein IIb / Q000276:immunology*; D011247:Pregnancy; D054098:Thrombocytopenia, Neonatal Alloimmune / Q000209:etiology* / Q000276:immunology
chemical_list: C044561:3a alloantigen, human; D016824:Antigens, Human Platelet; D007518:Isoantibodies; D007519:Isoantigens; D040201:Platelet Membrane Glycoprotein IIb