Increased HLA-DR homozygosity associated with pre-eclampsia

Abstract

It is generally accepted that maternal recognition of paternally derived fetal antigens occurs during normal pregnancy and may be beneficial for implantation and maintenance of gestation. Thus, we have investigated the human leukocyte class II DR antigens (HLA-DR), whose role in self and non-self recognition is well known, in women with pre-eclampsia, their partners and in control couples. The HLA-DR antigens were tested in 70 pre-eclamptic primigravidae women and their partners and 70 healthy control couples using the serological Terasaki technique. Our results did not show any particular HLA-DR antigen to be correlated with pre-eclampsia, but a statistically significant increase of only one identifiable HLA-DR antigen, which was presumed to express homozygosity at the HLA-DR locus, in the pre-eclamptic women and their partners: 67.1 versus 7. 9% in the control couples (P < 0.000001). The analysis of HLA-DR compatibility between pre-eclamptic women and their partners showed a statistically highly significant increase of the female-to-male compatibility (P = 0.0003) and a lower but significant male-to-female compatibility in comparison with controls (P = 0.014). From our results, it emerges that HLA-DR homozygosity and reduced antigenic disparity seem to be associated to a major risk for pre-eclampsia, which consequently appears to be a 'couple's disease'.

Maternal and fetal genetic factors account for most of familial aggregation of preeclampsia: A population‐based Swedish cohort study

“…This interpretation is congruent with a study by Kilpatrick et al [1990], which showed a strong association with sharing of HLA-DR4 between mother and fetus. Another recent study provides further evidence for the hypothesis that the HLA-DR compatibility between mother and fetus contribute to risk for preeclampsia [de Luca Brunori et al, 2000]. This interpretation of our data could explain previous inconsistent results of the importance of the HLA-system for preeclampsia [Kilpatrick, 1999;Lachmeijer et al, 2002].…”

Effect of HLA-compatibility in married couples on the development and severity of gestosis

“…Our results are in line with published data according to which HLA compatibility of parents by several HLA locuses 4.5-fold increases the risk of gestosis [6].…”

“…Numerous experimental and clinical studies demonstrated exceptionally important role of immune disorders in the pathogenesis of gestosis [2,4,6,9,12].…”

“…The degree of histocompatibility seems to be essential for the recognition of paternal HLA determinants inherited by the fetus, by maternal lymphocytes, which, in turn, leads to deficiency of cellular and humoral immunity in the mother-fetus system [6].…”

“…Experimental and clinical data on the effect of HLA identity of parents on the development of gestosis are contradictory [6,11].…”