Placental Alkaline Phosphatase Phenotypes Research Articles

The human placental immunoglobulin G receptor and immunoglobulin G transport

The objective of this study was to quantitatively determine an immunoglobulin G receptor, placental alkaline phosphatase, and its ligand immunoglobulin G in maternal and fetal blood and to study the transport capacity of the receptor. Venous blood samples from 66 term pregnant women and cord samples from their fetuses were obtained, together with the corresponding placentas. Mean placental alkaline phosphatase levels were determined to be 23.7 ng/ml and 1.2 ng/ml in maternal and fetal blood, respectively. Mean immunoglobulin G level of the fetal samples was significantly higher than that of the maternal samples (12.6 vs 9.5 gm/L, p < 0.0001). The placental alkaline phosphatase phenotype S had a larger dissociation constant to immunoglobulin G than did type F and was found to have mean fetal immunoglobulin G levels higher than those of the F type (13.3 vs 9.7 gm/L). The placental immunoglobulin G receptor placental alkaline phosphatase is found in the fetal circulation. The placental alkaline phosphatase phenotype was found to be related to the levels of its ligand immunoglobulin G in fetal blood, although the mechanism for this remains to be established. Immunoglobulin G is actively transported to fetal blood to reach higher levels than in the maternal circulation.

Determination of placental alkaline phosphatase phenotypes by starch-gel and acrylamide gel electrophoresis

The polymorphism of placental alkaline phosphatase (ALP) is usually studied by butanol extraction followed by starch gel electrophoretic separation at two different pH's, 8.6 and 6.0. Acrylamide gel electrophoresis (7.5%) in the presence of Triton X-100 is shown to be preferable in speed, reliability and reproducibility of results. All the placental ALP phenotypes detected had the same molecular mass by gradient acrylamide electrophoresis. The enzyme butanol extract is not sufficiently pure to enable the different placental ALP's to be distinguished by isoelectric focusing on polyacrylamide gels.

Immunochemical studies of human placental-type variants of alkaline phosphatase. Structural differences between the "Nagao isoenzyme" and the placental "D-variant".

Hyperimmune antisera raised against the rare FD and SD phenotypes of human placental alkaline phosphatase and the related cancer-associated Nagao isoenzyme were exhaustively absorbed with the common SS and FF phenotype enzymes conjugated to Sepharose. The antibodies so obtained had one of three specificities, determined by testing all the common phenotypes of placental alkaline phosphatase, the rare FD, SD and S-17 phenotypes, and five samples of purified cancer patient enzymes: (I) antibodies reactive with the S, D and I variant enzymes, but not with the F, 17 or Nagao enzymes; (II) antibodies reactive with the F, 17 and Nagao enzymes, but not with the S, D, and I variant enzymes; and (III) antibodies reactive with the D, 17 and Nagao enzymes and not with the S, F or I variant enzymes. Based on these data, and on the information obtained from biochemical characterization, it is argued that the Nagao isoenzyme and the D-variant are closely related but distinct enzymes. We propose a hypothetical scheme for the divergence of these two enzymes from a common ancestral gene product. In this scheme, an ancestral gene duplication resulted in two isoenzymes, one of which is completely specific to the placenta, and one of which (the "Nagao isoenzyme") has an unknown normal tissue localization, but is found in some cases of cancer. We use the term "syn-placental" to describe this latter isoenzyme, reflecting its close structural relationship to the placental isoenzyme.

Neonatal jaundice in ABO incompatible infants. Computer-assisted evaluation of risk of hyperbilirubinaemia and analysis of differences between sexes

A set of maternal and neonatal variables have been analyzed in a sample of ABO incompatible infants in order: (i) to attempt an evaluation, at birth, of the risk of hyperbilirubinaemia during the first few days of life and (ii) to elucidate the role of sex regarding the hyperbilirubinaemia in ABO incompatible infants. The following variables are included: Coombs test, gestational length, birth weight, birth order, ABO maternal phenotype, type of feto-maternal ABO incompatibility (A or B) and two factors of placental alkaline phosphatase (PAP) polymorphic system ( Pl f 1 and Pl 1 1 ). In males only the Coombs test showed a statistically significant contribution to the separation between infants with serum bilirubin level < 10 mg/dl and those with a level ≥10 mg/dl. In females the contribution of Coombs test and gestational length were highly significant and that of birth weight was very near the level of significance. Among female infants a group with a very slight risk of hyperbilirubinaemia (1%) can be separated at birth. This group comprises more than 50% of infants. In males the separation is much less useful. The present data indicate that although the overall frequency of hyperbilirubinaemia is very similar in ABO incompatible males and females, the set of variables considered are rather good predictors of serum bilirubin levels in females but not in males. Multivariate analysis also suggests that the two sexes may be very unlike concerning the pattern of relations among variables. In fact PAP phenotype appears a predictor of jaundice much more important in males than in females; on the contrary gestational length is very important in females but not in males.

Rare phenotypes of placental alkaline phosphatase. An analysis of relationships with some neonatal and maternal variables.

Placental alkaline phosphatase (Pl) polymorphism is due to the occurrence of three common alleles and more than fifteen rare ones at an autosomal locus. The high number and frequency (about 2%) of rare Pl alleles represent a very special case among polymorphic enzymes. Since the Pl gene is also special in that it is active only during intrauterine life, the allelic diversity and its maintenance may be connected with intrauterine environment and with fetal development.

Sex ratio in man: an analysis of the relationship with ABO blood groups and placental alkaline phosphatase phenotype.

Secondary sex ratio (SR) in man is influenced by various genetic and environmental factors. It has been observed that SR in subjects of blood group B compatible with their mothers is higher than in other subjects. The analysis of 676 newborns of the Rome population and 1,684 newborns of the New Haven (Connecticut) population have confirmed a higher SR in B group subjects compatible with their mothers. The data also indicate that placental alkaline phosphatase is another genetic factor influencing SR in man and that there is a strong interaction among ABO phenotype, fetomaternal ABO compatible status and PAP phenotype concerning their effects on SR.

Placental enzyme polymorphisms in Canadian populations. III. Alkaline phosphatase.

Placental alkaline phosphatase phenotypes have been determined for a large Canadian population. The 'common' alleles, PL1, PL2, and PL3 have frequencies similar to those of European populations. Five new phenotypes are described and the incidence of rare phenotypes is compared for several populations.

129: Gestational age, birth order and placental alkaline phosphatase

We have recently described an interaction between ABO and placental alkaline phosphatase (PAP) polymorphisms suggesting an important role of PAP in the maternal-foetal relationship. The present report is concerned with an analysis of 803 consecutive newborn infants from a Caucasian population of New Haven, Conn. U.S.A.. In first born infants PAP phenotype and gestational age were not related. In infants born from subsequent pregnancies the prevalence of S phenotype of PAP was significantly associated with gestational age (p<.01). Both in pre-term (≤37 weeks) and in post-term (≥42 weeks) infants the proportion of S phenotype was significantly lower than expected, suggesting a normalizing action of this phenotype on the duration of gestation. S phenotype is the homozygote for the allele which shows the highest frequency in all human populations. The present observation strongly suggest that PAP may have an important role in the maternal-foetal immunological relationship.

L-leucine, a specific inhibitor of a rare human placental alkaline phosphatase phenotype.

FISHMAN et al. reported that human placental alkaline phosphatase (Regan isoenzyme) was found in the serum and tumour tissue of a patient with lung cancer1. Two electrophoretically different variant forms of Regan alkaline phosphatase with a greater sensitivity to inhibition by L-leucine have since been described: the ‘Nagao isoenzyme’2, and a hepatoma-specific alkaline phosphatase3–5. Inglis et al.6 reported that the L-leucine-sensitive Nagao isoenzyme found in some cancer patients closely resembled the ‘D variant’ of human placental alkaline phosphatase, a rare phenotype defined electrophoretically on starch gel which is found in less than 1% of the general population of pregnancies7. An example was reported of a pregnancy serum D-phenotype enzyme presumably of placental origin, confirmed by electrophoresis established as L-leucine-sensitive6. Most interesting was the occurrence of the variant at high frequency in the ovarian cancer patients surveyed6,8. To extend the observations of Inglis et aL, screening for the phosphatases in placentae was carried out, both to establish the frequency of the L-leucine-sensitive placental phenotypes (which should match the frequency of the electrophoretically defined D variant phenotypes) and to provide enough enzyme to enable purification and characterisation. Supply of cancer tissue is generally restrictive for this purpose.

Immunological relationship between human placentae and intestinal alkaline phosphatase

Crystalline human alkaline phosphatase from placenta and intestine was isolated by butanol extraction, acetone precipitation, a heat step (for the placental enzyme), ammonium sulfate precipitation, anion exchange chromatography, gel filtration and crystallisation with ammonium sulfate. Rabbit antibodies showed a partial cross-reaction between both enzymes in double diffusion, quantitative precipitation experiments and in serial precipitin curves. There was no reaction with human alkaline phosphatases from liver, kidney and bone. Three phenotypes of placental alkaline phosphatase with different electrophoretical mobility exhibited identical immunological reactions with their respective antisera. Monospecific antisera were obtained by absorption with crystalline intestinal or placental alkaline phosphatase. These monospecific antisera against the placental or the intestinal alkaline phosphatase can be used for an immunological determination of these two alkaline phosphatases without contamination by other alkaline phosphatases in human serum.

Relationship between placental alkaline phosphatase phenotype and placental weight.

The relationship between placental alkaline phosphatase phenotype and placental weight was studied in a series of births from the University Hospital of Umea in northern Sweden. No significant effect

ABO incompatibility and its interaction with haptoglobins and placental alkaline phosphatase.

In a sample of 25 population groups, correlation coefficients were calculated between the proportion of AB0 blood-group incompatibility as well as the gene frequencies and haptoglobin and placental alkaline-phosphatase phenotypes and genotypes, separately. Correlation coefficients were also calculated between haptoglobin and placental alkaline phosphatase. A significant positive correlation was found between AB0 incompatibility and the PlF-gene frequency. There was a positive correlation between the Hp1-gene frequency and the 0 blood group, though no significant correlations were found between the proportion incompatibility and the Hp1-gene frequency. The results are discussed.

Carcinoplacental isoenzyme antigens

A carcinoplacental isoenzyme antigen is defined as a catalytically active protein present in a tumor, whose antigenic sites are identical to that of a protein present in the placenta but not in any fetal tissue. A family of placental isoenzymes of alkaline phosphatase (the Regan isoenzyme, the Nagao isoenzyme and Regan variant isoenzyme) is presented as examples of such antigens. Tumor alkaline phosphatases in humans have accordingly been classified as Regan or as non-Regan in type. Experimental evidence is described indicating that normal phenotypes of placental alkaline phosphatase appear in Regan-positive cancer sera. The D-variant phenotype which is considered rare in its occurrence in human placenta was frequently observed in Regan-positive cancer sera. In both pregnancy and cancer sera, D-variant phenotype correlated with marked enzyme inhibition by l-leucine. This latter characteristic is distinctive for the Nagao isoenzyme. In a case of ovarian cancer exhibiting both Regan and non-Regan isoenzymes, electron micrographs of tumor tissue processed for alkaline phosphatase showed sites of activity in the outer mitochondrial membranes, in the lateral cell borders and microvilli and in the dense-body type lysosomes. An array of mitochondria and endoplasmic reticulum resembling structures seen in placental cells was observed. A review of the literature has centered on polypeptide hormones in cancer, tumor morphology and hormone secretion, aberrant endocrine activity, α-fetoglobulin and carcinoembryonic antigen, enzymes in experimental cancer, tumor alkaline phosphatase and several theoretical considerations. The evidence is consistent with current views that normal genes are active in cancer. From the data and the previous literature, it is suggested that activation of placental and fetal genes may play a role in malignancy and that epigenetic rather than mutational mechanisms apply.

Interaction between placental alkaline phosphatase and ABO system polymorphisms. Effects on the clinical manifestations of feto-maternal ABO incompatibility.

Abstract. Placental alkaline phosphatase is a polymorphic glycoenzyme, produced by the fetal part of the placenta, which is found at an early stage of gestation and in considerable amount in the maternal bloodstream. Previous studies have shown an interaction of this polymorphism with that of ABO system during intrauterine life.In the present study the relationship between placental alkaline phosphatase phenotype and feto‐maternal isoimmunization in the ABO system was investigated. Isoimmunization was defined by a positive direct Coombs test on cord blood and/or jaundice in the neonatal period. In infants incompatible with their mothers in the B group, the incidence of the above‐mentioned signs of isoimmunization was lower in the presence of allele PIf1 of placental alkaline phosphatase. This relationship was not found in infants of group A.The present observations suggest that placental alkaline phosphatase may play an important role in the maternal‐fetal immunological relationships.

Properties of placental alkaline phosphatase. III. Thermostability and urea inhibition of isolated components of the three common phenotypes

Different heat inactivation rates were found among the three common homozygous human placental alkaline phosphatase phenotypes with respect to component I (the rapidly migrating component). Phenotype I1 was less stable than F1 and S1, while types F1 and S1 exhibited very similar thermostabilities, F1 being slightly more stable than S1. Components I, IIα (the fastest of the slow-moving components), and IIβ (the group of the very slowly migrating components) had different heat stabilities, IIβ being the most stable and I the least stable. Magnesium greatly increased the heat stability of all tested phenotypes. Placental alkaline phosphatase was found to be less heat resistant than reported previously. All phenotypes were equally inhibited over urea concentrations ranging from 0.5 to 8 m. No difference in the inhibition rate was found among components I, IIα, IIβ, and the crude placental butanol extract. The altered electrophoretic pattern of the crude placental extract obtained by urea starch gel electrophoresis was considered as being most likely due to reversible changes in the folding of the molecules.

Relationship between placental alkaline phosphatase phenotypes and the frequency of spontaneous abortion in previous pregnancies.

Previous results on an association between placental alkaline phosphatase phenotypes and the frequency of spontaneous abortion in a material from Uppsala in southern Sweden were confirmed in a hospita

Placental alkaline phosphatase phenotypes and pre-natal selection. Evidence from studies of spontaneous and induced abortions.

Placental alkaline phosphatase phenotypes were studied in extracts of chori onic tissue from spontaneous and induced abortions. In the series of spontaneous abortions the frequency of the Pl^f1 gene and of phenotypes having the F₁ factor was significantly higher than in the series of induced abortions and in the birth population. The over-representation of the F₁ factor was more pronounced in abortions after the 12th week of pregnancy. These results suggest that there exists a pre-natal selection against the Pl^f1 gene.

Interaction between Placental Alkaline Phosphatase and ABO System Polymorphisms

Placental alkaline phosphatase is a polymorphic glycoenzyme, produced by the fetal part of the placenta, which is found at an early stage of gestation and in considerable amount in the maternal bloodstream. Previous studies have shown an interaction of this polymorphism with that of ABO system during intrauterine life. In the present study the relationship between placental alkaline phosphatase phenotype and feto-matemal isoimmunization in the ABO system was investigated. Isoimmunization was defined by a positive direct Coombs test on cord blood and/or jaundice in the neonatal period. In infants incompatible with their mothers in the B group, the incidence of the above-mentioned signs of isoimmunization was lower in the presence of allele PI11 of placental alkaline phosphatase. This relationship was not found in infants of group A. The present observations suggest that placental alkaline phosphatase may play an important role in the maternal-fetal immunological relationships.

Comparison of thermostabilities of different human placental alkaline phosphatase phenotypes.

Comparison of thermostabilities of different human placental alkaline phosphatase phenotypes.

Placental alkaline phosphatase, relation between phenotype and enzyme activity.

The relation between placental alkaline phosphatase phenotype and enzyme activity was examined in pregnancy sera and placental extracts from a series of about 400 deliveries. The results from electrop