Evolution of Maternofetal Transport of Immunoglobulins During Human Pregnancy

Abstract

We determined the evolution of the maternal-fetal transport of immunoglobulins during human pregnancy. Paired blood samples were collected between 17-41 weeks of gestation (WG) by puncture of a peripheral maternal vein and by cordocentesis (17-36 WG, n = 91) or directly at delivery (37-41 WG n = 16) from the umbilical vein. Additional maternal samples were collected from the same individual (n = 16) at 10, 20, 30 WG, and at term. The concentration of IgG and its four subclasses and of IgA were determined in the sera using ELISA method. The mean level of IgG and IgA in maternal sera at 9-16 WG was 13.72 +/- 2.53 g/L and 3.95 +/- 1.23 g/L, respectively. Both, IgG and IgA throughout pregnancy decreased to a level of 60-70% (37-41 WG) of the initial concentration in early pregnancy. The ratio of IgG1:IgG2 in the maternal circulation was 2-3 and remained constant throughout pregnancy (17-41 WG). IgG3 and IgG4 levels remained constant and together were less than 10% of total IgG. In the fetal circulation a continuous rise in the level of both IgG and IgA was observed between 17 and 41 WG. Fetal level of IgG at 17-22 WG was only 5-10% of the maternal level and at term exceeded the maternal level reaching a value of 11.98 +/- 2.18 g/L. IgG1 at 17-22 WG was 0.93 +/- 0.42 g/L, which is approximately three times higher than IgG2. IgG1 showed an exponential rise and at 37-41 WG its concentration was seven times higher than IgG2. IgG3 and IgG4 also showed an exponential rise and at term reached a similar level as in the maternal circulation. Striking was the difference in results for IgG2 with a slow linear rise throughout gestation. The fetal IgG2 level at term remained significantly below the maternal concentration. The IgG subclasses when characterized according to the differences in transport capacity gave the following sequence: IgG1 > IgG4 > IgG3 > IgG2. Fetal IgA showed a slow linear rise with fetal levels at term remaining approximately 1,000 times lower than the concentration in the maternal circulation. Comparison of fetal and maternal levels of immunglobulines indicate that the human placenta during pregnancy develops a specific transport mechanism for IgG. There are differences for the four subclasses with preferential transfer of IgG1 while the slowest transfer is seen for IgG2.