Relevance of the HPA-15 (Gov) polymorphism on CD109 in alloimmune thrombocytopenic syndromes.
BACKGROUND
Alloantibodies against the human platelet (PLT) alloantigen (HPA)-15 system residing on CD109 can cause fetal and neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura, and PLT transfusion refractoriness. The detection of antibodies against HPA-15, however, is hampered by the variable low expression and instability of the CD109 molecule during preparation and storage.


METHODS
This study analyzed the occurrence of HPA-15 alloantibodies in 1403 patients: 930 FNAIT and 473 polytransfused (PT) patients by modified monoclonal antibody specific immobilization of PLT antigens (MAIPA) assay with well-defined phenotyped PLTs. A DNA typing technique was developed to confirm the phenotypes of PLT donors. B-cell lines were established as sources of reference DNA.


RESULTS
Genotyping of 407 unrelated blood donors revealed the gene frequencies 0.512 and 0.488 for HPA-15a and -15b, respectively. Based on the selection of PLTs expressing high amounts of CD109 on the surface (mean fluorescence intensity ratio 4-5 on expression peak on Days 2-4 after apheresis) antibody screening by the MAIPA assay was performed. In total, 16 (1.1%) HPA-15 alloantibodies were found comprising four anti-HPA-15a and 12 anti-HPA-15b. Anti-HPA-15b without other PLT-reactive antibodies were detectable in three serum samples of PT patients. The incidence of HPA-15 alloimmunization in PT patients was significantly higher than in mothers with FNAIT (3.0% vs. 0.22%). In relation to all detected HPA-specific antibodies, HPA-15 is responsible for 6.2 percent of alloimmunizations.


CONCLUSIONS
These observations indicate that alloimmunization against HPA-15 should be considered as a cause for immune thrombocytopenia, particularly in patients receiving multiple PLT transfusions.
Ertel
Katharina
K
Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
Al-Tawil
Milad
M
Santoso
Sentot
S
Kroll
Hartmut
H
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D016824:Antigens, Human Platelet / Q000235:genetics* / Q000276:immunology*; D005260:Female; D058851:GPI-Linked Proteins; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007518:Isoantibodies / Q000276:immunology; D008297:Male; D009363:Neoplasm Proteins; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000235:genetics* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016824:Antigens, Human Platelet; C120523:CD109 protein, human; D058851:GPI-Linked Proteins; D007518:Isoantibodies; D009363:Neoplasm Proteins