Beschreibung
Most cases of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are caused by maternal alloantibodies against paternally inherited human platelet antigen 1a (HPA-1a) expressed on fetal platelets. After placental transport of maternal IgG anti-bodies into fetal circulation, anti-HPA-1a may cause fetal thrombocytopenia. A fetal intracranial bleeding is feared, which occurs in approx. 10% of cases. The HLA-class II allele HLA DRB3*01:01 is associated with maternal immunization against HPA-1a. It is disputed whether this allele, possibly in combination with another HLA class II allele (HLA DRB4*01:01P), is associated with the severity of FNAIT.
A total of 101 mothers with FNAIT, caused by anti-HPA-1a antibodies, were exam-ined. Typing of HLA-DRB1, -DRB3, -DRB4, and –DRB5 genotypes were deter-mined by Luminex technology. Haplotype frequencies were compared between cases of FNAIT and 100 healthy controls. Platelet count in newborns (nadir) and the pres-ence of intracranial hemorrhage (ICH) were associated with estimated HLA class II haplotypes.
98% of the HPA-1a immunized mothers (99/101) carried at least one copy of HLA DRB3*01:01. Compared to controls, carriage of HLA-DRB3*01:01 was signif-icantly associated with immune response to HPA-1a [odds ratio (allele positivity) 92.3; 95 % CI 26.9–317.1; two-sided p ? 1,3 ? 10?12]. In contrast, there was no asso-ciation between HLA-DRB4*01:01P and immune response to HPA-1a. Furthermore, no association was found between HLA-DRB3*01:01 and HLA-DRB4*01:01P alone or in combination with the platelet count (nadir) of the affected newborns or the inci-dence of ICH. No other association between HLA-DRB alleles and FNAIT risk or severity was found.
HLA-DRB3*01:01 is associated with maternal immunization against HPA-1a. If this allele is missing, clinically apparent cases are very rare. A connection of the gene dose with the severity of fetal/neonatal thrombocytopenia or the occurrence of intra-cranial bleeding has not been demonstrated. The detection of HLA-DRB3*01:01 in screening programs would be useful to identify pregnant women at risk for immuniza-tion against HPA-1a.
