Pre-eclampsia is associated with HLA-DR4 sharing between mother and fetus

Full HLA-A,B and DR typing was carried out on 92 women with proteinuric pre-eclampsia, 80 of their husbands and 46 of their babies. The results were compared with corresponding data from 65 normotensive pregnancies involving primiparous women. The frequency of HLA-DR4 was increased in the pre-eclamptic women (RR 3.1; p less than 0.005) and in the babies of pre-eclamptic pregnancies (RR 2.6; p less than 0.03). The strongest association, however, was with sharing of HLA-DR4 between mother and fetus (RR 4.2; p = 0.01). There was no increase in HLA antigen sharing in general between spouses or maternal-fetal pairs in pre-eclampsia. Nor did pre-eclamptic women exhibit increased homozygosity in general at any HLA locus. We conclude that genetic susceptibility to pre-eclampsia depends at least partly on fetomaternal compatibility for a gene or genes associated with HLA-DR4.