Influence of human leukocyte antigen and tumour necrosis factor genes on the development of pre-eclampsia

Pre-eclampsia is a syndrome with a strong familial component. Autosomal rec essive inheritance acting only in the mother is not consistent with the epi demiological data, and a more complex genetic susceptibility, involving int eractions between maternal and fetal genomes, seems likely. The human leuko cyte antigen (HLA) system has been implicated, but many of the findings rep orted have been inconsistent or contradictory. Pre-eclampsia is unlikely to be the simple result of excessive HLA-class II antigen sharing between mot her and fetus, as was first thought, but a more complex mechanism involving fete-maternal compatibility cannot be excluded. The reported increase in H LA-DR4 in mothers and babies from pre-eclamptic pregnancies has not been in dependently confirmed for mothers, and no further studies-have been conduct ed with babies. Consequently, the allegedly stronger relationship with HLA- DR4 sharing between mother and fetus has neither been confirmed nor refuted . Certain (B44-DR7)-containing haplotypes appear to confer increased risk f or pre-eclampsia on the basis of independent analyses of American and Scott ish populations. HLA-DR53 may be associated with the antiphospholipid antib ody syndrome, which is itself a strong risk factor for pre-eclampsia, The t umour necrosis factor (TNF)-alpha allele, TNF1, may be associated with pre- eclampsia and certainly elevated concentrations of the cytokine appear to b e a feature of the disease. The inducibility of TNF-alpha is HLA-class II-d ependent, and the relevance of HLA-class II genes might be entirely in rela tion to TNF a synthesis and secretion.