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

作者：Kroll Hartmut^*; Feldmann Korinna; Zwingel Claudia; Hoch Jochen; Bald Rainer; Bein Gregor; Bayat Behnaz; Santoso Sentot

来源：Transfusion, 2011, 51(8): 1745-1754.

DOI：10.1111/j.1537-2995.2010.03038.x

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 (alpha(IIb)beta(3)) and GPIa/IIa (alpha(2)beta(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 C3347T 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.
CONCLUSION: 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.

• 出版日期2011-8