IgG placental transfer in healthy and pathological pregnancies

Abstract

Placental transfer of maternal IgG antibodies to the fetus is an important mechanism that provides protection to the infant while his/her humoral response is inefficient. IgG is the only antibody class that significantly crosses the human placenta. This crossing is mediated by FcRn expressed on syncytiotrophoblast cells. There is evidence that IgG transfer depends on the following: (i) maternal levels of total IgG and specific antibodies, (ii) gestational age, (iii) placental integrity, (iv) IgG subclass, and (v) nature of antigen, being more intense for thymus-dependent ones. These features represent the basis for maternal immunization strategies aimed at protecting newborns against neonatal and infantile infectious diseases. In some situations, such as mothers with primary immunodeficiencies, exogenous IgG acquired by intravenous immunoglobulin therapy crosses the placenta in similar patterns to endogenous immunoglobulins and may also protect the offspring from infections in early life. Inversely, harmful autoantibodies may cross the placenta and cause transitory autoimmune disease in the neonate.

Figure 1

IgG transfer from the mother to the fetus occurs during pregnancy across the syncytiotrophoblasts of the placenta. Syncytiotrophoblasts are bathed in maternal blood and internalize maternal IgG in endosomes. FcRn is expressed on the internal surfaces of the endosome. Upon acidification in the endosome, maternal IgG bound to FcRn is protected from degradation by lysosomal enzymes and then is transcytosed. The endosomes fuse with the membrane on the fetal side of the syncytiotrophoblast, where the physiological pH promotes the dissociation of IgG from FcRn to the fetal circulation. High levels of IgG antibodies cause IgG degradation due to the saturation of FcRn receptors.

Figure 2

Correlation indexes and placental transfer ratios of maternal and term cord blood IgG levels reactive with tetanus toxoid, O111 LPS from enteropathogenic E. coli and Hib polysaccharide. Correlation indexes and placental transfer is higher to thymus-dependent antigens, as tetanus toxoid than to thymus-independent antigens type I and II, as LPS and polysaccharides, respectively.

Figure 3

Percentages of placental transfer ratios of IgG subclasses delivered to preterm and term newborns in different gestational weeks. IgG1 and IgG3 transfer ratios rose with increasing gestational age, with IgG1 showing a peak transfer ratio at 37 weeks of pregnancy. IgG2 transfer ratios are always lower than the other IgG subclasses [52].

Figure 4

Immunoblotting of anti-EHEC O157:H7 IgG antibodies in the paired maternal and cord samples. Bacterial proteins were separated by 12.5% SDS-PAGE. Paired maternal and cord serum samples are identified numerically. M: maternal serum; C: cord serum; NHS: pool of healthy adult serum samples (normal human serum). The immunoblots were developed with antihuman IgG conjugate. Molecular weight standards are on the left for samples 1–8 and on the right for the pool of normal human serum. It was observed that there is almost complete identity between the antigens recognized by maternal and umbilical cord sera [58].

Figure 5

Total IgG concentrations in cord serum samples from newborns in different gestational weeks [46, 60]. *Number of samples in each period.