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

Abstract

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.

Maternal Ethnicity, Paternal Ethnicity, and Parental Ethnic Discordance

“…As far as the fetoplacental unit's contribution is concerned, pregnancies with maternal-fetal HLA-DR4 concordance further increased the risk of preeclampsia as compared with presence of HLA-DR4 in the mother alone. 11 When we consider ethnicity and its association with preeclampsia, certainly genetic polymorphisms are one possible cause for differences in the prevalence of the disease among different ethnic groups. Genetic polymorphisms, for example in genes associated with the clotting cascade, have been associated with varying prevalence of preeclampsia.…”

HLA Antigens in patients with severe preeclampsia

“…Several researchers have attempted to ascertain the possible existence of an association between antigens of the HLA system and the development of preeclampsia [5,7,11,12,14]. Their studies were conducted on the basis of the two premises that preeclampsia possesses both an immunologic and a genetic background component and that the HLA system is often useful in delineating the immunogenetic basis of some diseases.…”

“…The suggestion that autoimmune mechanisms are involved in the genesis of preeclampsia has gained increasing support [4,8,17,18,19]. Several studies have attempted to disclose the possible association between antigens of the HLA system and development of preeclampsia [5,7,11,12,14], as the HLA antigen system is known to be useful in examining the immunogenetic basis of some diseases. In this study the distribution of HLA antigens in patients with severe preeclampsia was analyzed in the Niigata district of Japan.…”

Maternal immunization by husband's leukocytes for repeated fetal death associated with mild pre-eclampsia — case report with successful outcome

“…The susceptibility to pre-eclampsia/eclampsia itself is hereditary [15], but seems further influenced by the fetal genotype, with the genes acting in the fetus being linked to HLADR4 [16]. Moreover, the existence of HLA-linked genes causing susceptibility to both idiopathic abortion and intrauterine fetal death has been suggested because of the observation that the rate of fetal losses beyond 28 weeks in sisters sharing HLA haplotypes with recurrent aborters was significantly above that in other sisters [17].…”