Susceptibility to alloimmunization to platelet HPA-1a antigen involves TAP1 polymorphism.
The alloimmunization against platelet HPA-1a antigen in mothers of thrombocytopenic neonates is strongly associated with HLA class II structures (DR3 and DR13) and especially with HLA-DR52a antigen (98% of the cases reported here). Because new genes have recently been mapped within the MHC class II region, we typed TAP1 and TAP2 gene polymorphisms by ARMS-PCR in order to characterize more effectively MHC genes involved in this alloimmunization. Our results showed that TAP1*0102 allele was significantly associated with NAIT only in the population of HLA-DR 13-DR52a-immunized women (50%) versus HLA-DR 13-DR52a controls (20%) (p < 0.05), and not in HLA-DR3-DR52a-immunized women versus HLA-DR3-DR52a controls. There is no linkage disequilibrium between TAP1*0102 and DRB1*13 alleles (delta = -0.0063) that could account for this result. The higher frequency of TAP1*0102 allele among HLA-DR 13-DR52a-immunized women suggests that HPA-1a antigen presentation and recognition may be influenced by nonclassic HLA class II gene polymorphisms, or that other linked but yet unknown genes could interfere.
Regional Center for Blood Transfusion, Nantes, France.
V
V
Braud
D
D
Chevrier
A
A
Cesbron
J D
JD
Bignon
C
C
Kaplan
N
N
Valentin
J Y
JY
Muller
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D016824:Antigens, Human Platelet / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D005260:Female; D006681:HLA-D Antigens / Q000235:genetics*; D006682:HLA-DP Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D039661:Integrin beta3; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D013921:Thrombocytopenia / Q000235:genetics / Q000276:immunology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D016824:Antigens, Human Platelet; D006681:HLA-D Antigens; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; C061248:ITGB3 protein, human; D039661:Integrin beta3; C073119:TAP1 protein, human; C071692:TAP2 protein, human