Frequency and Determinants of Pregnancy‐Induced Child‐Specific Sensitization

The aim of this study was to define the frequency and determinants of pregnancy‐induced child‐specific sensitization shortly after full‐term delivery using sensitive single HLA‐antigen beads (SAB) and high resolution HLA‐typing of the mothers and their children (n = 301). A positive SAB result was defined by a background normalized ratio >1 or a mean fluorescence intensity (MFI) >300, >500 and >1000, respectively. The overall frequency of pregnancy‐induced sensitization determined by SAB shortly after full‐term delivery was between 45% (MFI > 1000 cut‐off) and 76% (ratio cut‐off). The rate of child‐specific sensitization at the HLA‐A/B/C/DRB1 loci was between 28% (MFI > 1000 cut‐off) and 38% (ratio cut‐off). The number of live birth was associated with a higher frequency of sensitization, which was driven by child‐specific, but not third party HLA‐antibodies. There was a clear hierarchy of sensitization among the investigated loci (B‐locus: 31%; A‐locus: 26%; DRB1‐locus: 20%; C‐locus: 15%; p < 0.0001). Some mismatched paternal HLA‐antigens led to a significantly higher rate of sensitization than the average (e.g. HLA‐A2, HLA‐B49, HLA‐B51, HLA‐C*15). Furthermore, the mother's own HLA‐phenotype—especially HLA‐A/B homozygosity—was associated with a higher rate and broadness of sensitization. The number of mismatched HLA‐A/B/C eplets strongly correlated with the rate of child‐specific class I sensitization. Using current technology, pregnancy‐induced sensitization shortly after full‐term delivery is present in over 45% of mothers and depends on the number of live births, specific paternal HLA‐antigens, and the mother's own HLA‐phenotype.