title: A new platelet alloantigen, Swi(a) , located on glycoprotein Ia identified in a family with fetal and neonatal alloimmune thrombocytopenia.
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).
  
  
  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 (α(IIb) β(3) ) and GPIa/IIa (α(2) β(1) integrin), indicating the presence of anti-HPA-1a and an additional alloantibody against GPIa (termed anti-Swi(a) ).
  
  
  RESULTS
  By immunochemical studies, the localization of the Swi(a) antigen on GPIa/IIa could be confirmed. Analysis of paternal GPIa full-length cDNA showed a single-nucleotide substitution C(3347) T in Exon 28 resulting in a Thr(1087) Met 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 Swi(a) carriers. Expression studies on allele-specific transfected Chinese hamster ovary (CHO) cells confirmed that the single-amino-acid substitution Thr(1087) Met was responsible for the formation of the Swi(a) epitope. Adhesion of CHO cells expressing the Swi(a) alloantigen to immobilized collagens was not impaired compared to the wild-type control and was not inhibited by anti-Swi(a) alloantibodies.
  
  
  CONCLUSIONS
  In this study we defined a new PLT alloantigen Swi(a) 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.
authors.affiliation: Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau, Germany. hartmut.kroll@bsd-nstob.de.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kroll
authors.forename: Korinna
authors.initials: K
authors.lastname: Feldmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Zwingel
authors.forename: Jochen
authors.initials: J
authors.lastname: Hoch
authors.forename: Rainer
authors.initials: R
authors.lastname: Bald
authors.forename: Gregor
authors.initials: G
authors.lastname: Bein
authors.forename: Behnaz
authors.initials: B
authors.lastname: Bayat
authors.forename: Sentot
authors.initials: S
authors.lastname: Santoso
mesh_terms: D000818:Animals; D016824:Antigens, Human Platelet / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification* / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005190:Family; D017809:Fatal Outcome; D005260:Female; D005333:Fetus / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D039421:Integrin alpha2 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D039661:Integrin beta3; D008297:Male; D010375:Pedigree; D011247:Pregnancy; D054098:Thrombocytopenia, Neonatal Alloimmune / Q000235:genetics / Q000276:immunology*
chemical_list: D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D039421:Integrin alpha2; D039661:Integrin beta3