Genetic susceptibility and anti-human platelet antigen 5b alloimmunization role of HLA class II and TAP genes.
Platelet alloimmunization may result in post-transfusion purpura, and during pregnancy may cause neonatal alloimmune thrombocytopenia (NAIT), with a frequency estimated at 1.3 per 1000 live births. The risk of morbidity is significant: 20% of affected infants have neurologic sequelae and the death rate is about 10%. A better understanding of the immune response to platelet alloantigens would allow for a better definition, and thus better management of pregnant women at high risk. Limited data are available on the immune response against HPA-5b, the second most frequent antigen, after HPA-1a, implicated in NAIT. We studied HLA class II and TAP gene polymorphism in 50 women immunized against HPA-5 system antigens. Our results suggest a strong association of alloimmunization with a cluster of HLA DR molecules sharing a particular polymorphic amino acid sequence at position 69-70 (Glu-Asp encoded by GAA-GAC nucleotide sequence) of the DR beta 1 chain (RR = 2.95, RR = 5.70 when patients were homozygous for this sequence), and a negative association with the DRB1*0301 allele (2.1% vs. 28%; RR = 0.08). Furthermore, increased frequency of a TAP2 dimorphism at position 379 was observed in immunized women against the HPA-5 antigens (RR = 4.7).
Semana
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Laboratoire Universitaire d'Immunologie, C.R.T.S., Rennes, France.
Zazoun
T
T
Alizadeh
M
M
Morel-Kopp
M C
MC
Genetet
B
B
Kaplan
C
C
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*; D000595:Amino Acid Sequence; D016824:Antigens, Human Platelet / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D006681:HLA-D Antigens / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007518:Isoantibodies / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology; D011110:Polymorphism, Genetic / Q000235:genetics; D011247:Pregnancy; D013921:Thrombocytopenia / Q000235:genetics*
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; D001323:Autoantibodies; D006681:HLA-D Antigens; D007518:Isoantibodies; D007519:Isoantigens; D019038:Platelet Glycoprotein GPIb-IX Complex; C073119:TAP1 protein, human; C071692:TAP2 protein, human