Abstract
In pregnancies achieved after egg donation (ED) tolerance towards a completely allogeneic fetus is mediated by several complex immunoregulatory mechanisms, of which numerous aspects are still unknown. A distinct lesion not described previously in the literature, was repeatedly found in the chorionic plate in a substantial portion of placentas from ED pregnancies, but never in placentas from normal term pregnancies. The aim of this study was to assess its origin and its cellular composition. The relation between the lesion, the clinical and histological parameters were assessed. In addition we investigated the relation with the number of HLA-mismatches and KIR genotype of mother and child.In ten out of twenty-six (38.5%) placentas from ED pregnancies an inflammatory lesion was present in the chorionic plate. A significantly lower incidence of pre-eclampsia was found in the group with the lesion; 0% versus 45.5%. A significant relation was found between this lesion and the presence of intervillositis, chronic deciduitis, presence of plasma cells and fibrin deposition in the decidua. Fluorescent in situ hybridisation with X/Y-chromosome probes showed that the majority of cells present in the lesion are of maternal origin. The expression of the macrophage marker CD14+ and of the type 2 macrophage (M2) marker CD163+ was significantly higher in the lesion. The incidence of a fetal HLA-C2 genotype was significantly higher in cases with a lesion compared to the group without the lesion. In conclusion, a striking relationship was observed between the presence of a not previously described inflammatory lesion in the chorionic plate and the absence of pre-eclampsia in ED pregnancies. The lesion consists of mainly maternal cells with a higher expression of the macrophage marker CD14+ and the M2 marker CD163+. These findings suggest a protective immune mechanism which might contribute to the prevention of severe clinical complications like pre-eclampsia.
Highlights
During pregnancy the maternal immune system does not reject the fetus even though allogeneic paternal HLA antigens of the fetus are recognized by the maternal immune system
We observed a striking relationship between the presence of a not previously described lesion in the chorionic plate and the absence of pre-eclampsia, a relatively common complication in egg donation (ED) pregnancies [3]
This report suggests an immunological protective mechanism in the chorionic plate of maternal cells directed against paternal antigens present in the fetal tissue
Summary
During pregnancy the maternal immune system does not reject the fetus even though allogeneic paternal HLA antigens of the fetus are recognized by the maternal immune system. Tolerance to the semi-allogeneic fetus is mediated by several complex immunoregulatory mechanisms, of which numerous aspects are still poorly understood [1]. Even more intriguing are pregnancies achieved after egg donation (ED) in which the maternal immune system must maintain tolerance towards an often completely allogeneic fetus. The increased risk of pre-eclampsia [2,3] and a higher incidence of placental pathological lesions, such as chronic villitis of unknown etiology, chronic deciduitis and massive chronic intervillositis, found in ED cases is probably based on a dysregulation of the local immune response at the fetal-maternal interface [4,5]. Decidual macrophages are thought to play an important regulatory role at the fetal-maternal interface. M2 macrophages are involved in tissue remodeling and inhibit inflammation [7] and believed to be important for the maintenance of the tolerance to the non-self semi-allogeneic fetus [8]
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