Alloimmunization to platelet antigen HPA-1a (PIA1) is strongly associated with both HLA-DRB3*0101 and HLA-DQB1*0201.
Antibodies to the platelet HPA-1a antigen can elicit in the newborn a condition known as neonatal alloimmune thrombocytopenic purpura (NAITP). Previous studies based on RFLP analysis showed that 100% of HPA-1a-negative women who produced anti-HPA-1a antibodies (responders) were HLA-DRw52a (DRB3*0101). However, this specificity could also be found in some HPA-1a-negative women not producing anti-HPA-1a antibodies (nonresponders). We have analyzed in detail by PCR-SSOP the HLA-DR, -DQ, and -DP loci of 36 responders and 10 nonresponders. We found that while the allele DRB3*0101 was present in the vast majority of responders (91%), there were exceptions. Furthermore, the DQB1*0201 allele was found to be present in almost all responders (94%), but again was also found in nonresponders. The risk of alloimmunization to HPA-1a in an HPA-1b homozygous mother significantly increases with the presence of either allele, the odds ratio being 39.7 for DQB1*0201 and 24.9 for DRB3*0101. Sequencing of exon 2 of these two alleles from responders indicated no sequence difference when compared with the consensus sequences. This indicates that they do not represent variants when compared with the same alleles found in some nonresponders.
Blood Services, Canadian Red Cross Society, Montreal Center, Quebec.
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L'Abbé
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Tremblay
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Filion
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Busque
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Goldman
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Chartrand
D000483:Alleles; D016824:Antigens, Human Platelet / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059826:HLA-DRB3 Chains; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007114:Immunization; D015994:Incidence; D007231:Infant, Newborn; D007518:Isoantibodies / Q000276:immunology; D008431:Maternal-Fetal Exchange; D008969:Molecular Sequence Data; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D011696:Purpura, Thrombocytopenic / Q000151:congenital* / Q000453:epidemiology / Q000276:immunology
D016824:Antigens, Human Platelet; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059826:HLA-DRB3 Chains; D007518:Isoantibodies; D010980:Platelet Membrane Glycoproteins