Immunogenetic determinants in recurrent miscarriage – evidence from genetic-epidemiological research

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Abstract

Immunological disturbances probably play a major role in the etiology of recurrent miscarriage (RM) – however, a detailed insight in the immunological processes going on is difficult because the most important interactions take place locally in the uterus during pregnancy at the feto–maternal interface. The study of the role of the impact of polymorphic immunogenetic determinants in RM has advantages compared to the study of humoral or cellular immunological factors locally or systemically: genetic polymorphisms can be determined unambiguously using DNA technology, polymorphisms associated with RM are expected to influence immunological processes also locally in the uterus and the finding of an increased prevalence of specific immunogenetic polymorphisms in RM cannot be deduced as a result of RM but may be a cause of the syndrome.

We have investigated polymorphisms in the genes coding for HLA-DR, HLA-DQ, HLA-G and mannan-binding lectin (MBL) in patients with RM and in controls and investigated the impact of RM-associated polymorphisms on the outcome of future pregnancies. Furthermore, we have investigated the impact of the gender of the first child on future pregnancy outcome in patients with secondary RM.

The case–control studies and the prospective studies provide evidence that specific maternal class II HLA alleles or genotypes, specific combinations of HLA-G alleles in the RM couples, genes coding for low MBL concentrations and male-specific minor histocompatibility antigens (HY-antigens) play a role in the pathogenesis of RM.

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