The alloimmune response to the human platelet antigen-1a is not related to maternal-fetal killer immunoglobulinlike receptor/HLA-Cw combinations.
BACKGROUND
Human platelet antigen (HPA)-1a fetomaternal alloimmune thrombocytopenia, responsible in the most severe cases for fetal or neonatal intracranial hemorrhages leading to death or survival with neurologic sequelae, was shown to be restricted to the human leukocyte antigen (HLA) Class II DRB3*0101-encoded molecule. Whereas more than 90 percent of alloimmunized mothers display the DRB3*0101 allele, the positive predictive value of the presence of DRB3*0101 is only 35 percent. Additional genetic risk factors may exist of which elucidation could improve the undertaking of incompatible pregnancies in at-risk families, encouraging an antenatal screening. Interactions of killer immunoglobulinlike receptors (KIRs) on maternal decidual NK cells with HLA-Cw molecules on fetal trophoblasts were reported as one of the mechanisms involved in the fetomaternal tolerance during pregnancy.


METHODS
Genotyping was performed of 16 KIR genes in HPA-1a-negative/DRB3*0101-positive alloimmunized mothers and in HPA-1a-negative/DRB3*0101-positive nonimmunized mothers as well as HLA-Cw genotyping in thrombocytopenic children and their nonaffected siblings.


RESULTS
No particular KIR genes or KIR genotypes were observed in the alloimmunized or nonimmunized mothers. Distribution of HLA-Cw genes in affected infants and nonaffected siblings did not reveal any HLA-Cw specificity associated with triggering or modulation of the HPA-1a alloimmunization. No maternal KIR/fetal HLA-Cw combinations were demonstrated in association with a detrimental or a protective effect on the HPA-1a alloimmunization.


CONCLUSIONS
Maternal KIR/fetal HLA-Cw gene combinations that are involved in the fetomaternal tolerance do not appear to play a role in the HPA-1a alloimmunization.
Valentin
Nathalie
N
Laboratoire d'Immunologie, Institut de Biologie, CHU Nantes, France. nathalie.valentin@chu-nantes.fr
Gagne
Katia
K
Kerdudou
Nolwenn
N
Hallé
Liliane
L
Kaplan
Cécile
C
Killie
Mette Kjaer
MK
Skogen
Bjorn
B
Muller
Jean-Yves
JY
Bignon
Jean-Denis
JD
D016824:Antigens, Human Platelet / Q000276:immunology*; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D039661:Integrin beta3; D007518:Isoantibodies / Q000276:immunology; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology
D016824:Antigens, Human Platelet; D006680:HLA Antigens; C061248:ITGB3 protein, human; D039661:Integrin beta3; D007518:Isoantibodies; D054340:Receptors, KIR