Transport of proteins across the human placenta

PROBLEM: The transport of various proteins across the human placenta was in vestigated by comparing maternal and fetal concentrations of tetanus antige n (TT-AG), anti-tetanus (TT)-immunoglobulin G (IgG) (following maternal vac cination), IgA, human chorionic gonadotropin (hCG), human placental lactoge n (hPL), and alpha-fetoprotein (AFP) at term. METHOD OF STUDY: The concentrations of the six proteins were determined usi ng enzyme-linked immunosorbent assay in serum of maternal venous and umbili cal (fetal) vein samples obtained at delivery from uncomplicated term pregn ancies (n = 16). RESULTS: The ratios (mean +/- standard deviation) of fetal (umbilical) to m aternal level were 1.41 +/- 0.33 (anti-TT-IgG), 0.91 +/- 0.37 (TT-AG), 0.00 2 +/- 0.001 (IgA), 0.003 +/- 0.001 (hCG), and 0.008 +/- 0.004 (hPL), while the maternal:fetal concentration ratio of AFP was 0.002 +/- 0.002. IgA, hCG , hPL, and AFP showed a close correlation between maternal and fetal levels varying between r(2) = 0.47 to 0.73 (P < 0.004-0.0001). Because AFP is pro duced by the fetus while IgA originates in the mother, the appearance of sm all amounts of these two proteins in the maternal or fetal compartment, res pectively, suggests a slow rate of diffusion following a high concentration gradient. The detection of hCG and hPL in fetal serum is also interpreted as diffusion from the maternal into the fetal blood. Anti-TT-IgG has a sign ificantly higher concentration in the fetal as compared with the maternal s erum, which is in line with the well-documented active transfer of IgG. Fet al TT-antigen levels were similar to maternal concentrations, showing a clo se correlation (r(2) = 0.74, P < 0.0001) between the two proteins. CONCLUSIONS: The correlation between maternal and fetal concentrations of v arious proteins like IgA (150,000 Da), hCG (42,000 Da), and hPL (21,000 Da) suggests passive diffusion of these macromolecules across the placenta fro m the maternal to the fetal side, albeit at a slow rate. A similar process is postulated for AFP (70,000 Da) diffusing in the opposite direction from the fetus to the mother. There was no significant difference between the tr ansplacental fetomaternal gradient of IgA and hCG and the maternal-fetal gr adient of AFP. In view of the substantially larger volume of circulating ma ternal as compared with fetal blood, a significantly higher rate of crossin g of AFP as compared with the other proteins must be assumed. It is uncerta in whether a difference in die rate of transplacental transfer in the two d irections or an additional source of AFP production in the maternal compart ment explains the high maternal level. Anti-TT-IgG concentration is signifi cantly higher in fetal than in maternal serum suggesting active transfer fr om the mother to the fetus. Furthermore, there is considerable transfer of TT-AG and a close correlation of fetal:maternal ratios of anti-TT-IgG (150, 000 Da) and TT-AG (150,000 Da) could be an indication for a specific transf er of the antigen antibody complex.