Pregnancy-specific 1-glycoprotein Research Articles

Massive Cutaneous Hyalinosis: Identification of the Hyalin Material as Monoclonal Kappa Light Chains, Adhesive 90 kD Glycoprotein, and Type I Collagen

The hyalin material in massive cutaneous hyalinosis, a disease characterized by extensive tumorous periodic acid-Schiff-(PAS) positive extracellular cutaneous deposits, has been elucidated by biochemical and immunologic methods. Three major components were found: kappa light chains, a mannose-rich glycoprotein, and type I collagen. Trace amounts of fibrinogen, fibronectin, laminin, IgG, pregnancy-specific glycoprotein, albumin, and keratan sulfate, but not keratin, were also present. The kappa light chains were monoclonal, cryoprecipiting, and more basic than the kappa chains from two myeloma patients. The glycoprotein, which could not be identified as any known glycoprotein, had an apparent molecular weight of 90,000 D. Amino acid analysis showed that glutamic acid, aspartic acid, leucine, and threonine were abundant, whereas hydroxyproline, hydroxylysine, and sulfhydryl amino acids were absent. The carbohydrate content of the protein was approximately 20%. The major monosaccharides were mannose and N-acetylglucosamine. Galactose, N-acetylneuraminic acid and fucose also were present. The third major component of the hyalin material was identified as type I collagen. A humoral immune response to the storage material was found: the patient's serum contained IgM and IgG class antibodies against the mannosylglycoprotein (90 kD glycoprotein) and against type I collagen.

Biological markers in human lung carcinoma: an immunopathological study of six antigens.

Immunohistological methods were used to investigate the presence of calcitonin, thyrotrophin, carcinoembryonic antigen, beta pregnancy specific glycoprotein, human placental lactogen, and the beta subunit of human chorionic gonadotrophin in formalin fixed lung tumour tissue sections. Carcinoembryonic antigen was observed in 71% of 101 tumours studied (70%), beta 1 pregnancy specific glycoprotein in 66 of 97 tumours (68%), beta subunit of human chorionic gonadotrophin in 35 of 97 (36%), human placental lactogen in 19 of 97 (20%), calcitonin in 10 of 71 (14%), and thyrotrophin in one of 27 lung tumours studied. There appeared to be no direct association between the presence of any given marker and the presence of any other. Similarly, the association between the presence of a tumour marker and histological type was poor. This study shows that the presence of tumour markers is relatively common in human lung tumours.

SP-1 in normal and complicated early pregnancy. Diagnosis by enzyme immunoassay

Pregnancy specific glycoprotein SP-1 was measured by enzyme immunoassay Enzygnost in patients with diagnosis of haemorrhage in early pregnancy. Results were compared with a normal range between 6.-22. week of gestation (n = 268) and were analysed for their predictive value in determining prognosis. 24 of 27 cases with levels below the normal range had an abortion (88,9%) while 28 of 31 women with continuing pregnancies had levels within normal range (90,3%).

Use of Circulating Pregnancy-Specific β1 Glycoprotein as a Marker in Carcinoma of the Breast in Women<xref ref-type="fn" rid="fn2">2</xref>

Pregnancy-specific beta 1 glycoprotein (SP1) was determined by radioimmunoassay in sera from 27 normal women, 33 women with benign breast disease, and 191 women with carcinoma of the breast, staged for extent of the disease. All diagnostic groups exhibited substantial overlap in SP1 values. Those with benign breast diseases tended to have values at least as high as those with cancer. Normal patients tended to have slightly lower values, but this difference may well have been due to the younger ages of the normal patients in our sample, because SP1 values tended to increase with age. Immunochemical dilutions of SP1 in the serum with the highest value (10.2 ng/ml) did not differ significantly from standard placental SP1.

Measurement of plasma placental proteins and estriol in the detection of intrauterine growth retardation

This study was designed as an assessment of the clinical value of total estriol, placental lactogen (hPL), pregnancy specific glycoprotein (SP1), pregnancy-associated plasma protein-A (PAPP-A) and placental protein 5 (PP5), measured in a single sample of maternal serum, in the detection of intrauterine growth retardation (IUGR) in a large series of high risk pregnancies. Our results show the highest detection rate with SP1 (51%) and second highest with hPL (35%); estriol was less useful while PAPP-A and PP5 were of no value. However, there were 31% of false positives with SP1 compared with 14% for hPL. The best combination of the five parameters for the diagnosis of IUGR was achieved by measurement of both SP1 and hPL, with a low concentration of either protein indicating IUGR (sensitivity 63%, specificity 63%).

Comparative assays in three laboratories of serum specimens containing pregnancy-specific β1 glycoprotein with different proportions of the α variant

Following several reports that the α component of pregnancy-specific β 1 glycoprotein (SP1) gives dose-response curves that are flatter than those of the β component when assayed by radioimmunoassay of the competitive type, a collaborative study was carried out by 3 laboratories to examine whether radial immunodiffusion or rocket immunoelectrophoresis give a similar result. Five sera from pregnant women at the 34–39th week of gestation with β : α ratios of 0.8–4.7 were assayed by both the latter methods against either the IARC 78 610 reference preparation or the SP1 Behring standard. When preparations were assayed by rocket immunoelectrophoresis (two laboratories), the dose-response curves were parallel. When preparations were assayed by radial immunodiffusion (two laboratories), parallelism was observed (one laboratory) after the addition of polyethylene glycol, the presence of which is necessary to visualize immune precipitates in which α is involved. Discrepancies observed when methodologies such as competitive radioimmunoassay are used, in which there are limited amounts of antibodies, are explained, at least partially, by the fact that the β component has a greater relative affinity for the antibody as higher concentrations of β : α mixtures are assayed. However, when antibody is present in excess, as in radial immunodiffusion and rocket immunoelectrophoresis, no such difference in affinity seems to occur.

Differentiation of human breast carcinomas: an immunohistological study of appropriate and inappropriate protein production.

Secretory piece of immunoglobulin A, a product of normal breast tissue, and beta 1 pregnancy-specific glycoprotein, a product of syncytiotrophoblast of placenta, have been demonstrated in breast carcinomas by an indirect immunoperoxidase method. A close relationship has been found between the site of staining within cells and tumour structure for both secretory piece, the appropriate protein, and beta 1 pregnancy-specific glycoprotein, the inappropriate protein. The reaction was at the periphery of cells in areas of tubular differentiation and was diffusely intracytoplasmic in solid groups of tumour cells. The poorly differentiated carcinomas have a low incidence of detection for both antigens but the tumours showing good histological differentiation appear to be functionally heterogeneous with some being negative for both proteins, some staining for the appropriate secretory piece of immunoglobulin A and the inappropriate beta 1 pregnancy-specific glycoprotein and only one out of 12 producing the appropriate protein alone.

Placental proteins and steroid hormones in the soluble fraction of human syncytiotrophoblast plasma membrane.

Placental protein 5 (PP5), pregnancy-specific glycoprotein (SP1), pregnancy-associated alpha 2-glycoprotein (SP3) and chorionic gonadotrophin could not be demonstrated in appreciable molar quantities in the soluble fraction from microvillous plasma membrane preparations isolated from the syncytiotrophoblast of full-term human placentae. However, progesterone, total oestriol and placental lactogen may have some association with this membrane.

The ratio between molecular variants of pregnancy-specific β1 glycoprotein (SP 1) in the peripheral and retroplacental circulation during late pregnancy

The ratio between two molecular variants of pregnancy-specific beta 1 glycoprotein (SP1) in the peripheral and retroplacental circulation was analysed in nine women during late pregnancy. The ratio between the two molecular variants, i.e. SP1 beta and SP1 alpha, was found to be identical in the peripheral and retroplacental circulation in all women examined. Comparisons were also made between SP1 beta as measured by radioimmunoassay and a normal serum protein, alpha 2 macroglobulin. A positive concentration gradient from peripheral to retroplacental circulation was found for SP1 beta whereas the gradient was less pronounced for alpha 2 macroglobulin. These findings add weight to the concept that SP1 alpha is a unique molecular species and not a genetic variant or a product of SP1 beta.

Molecular heterogeneity of pregnancy specific β1 glycoprotein: The effect on measurement by radioimmunoassay and electroimmunoassay

A comparison of methods for the quantification of circulating pregnancy specific β1 glycoprotein in late pregnancy was performed to assess the influence of the presence of a high molecular weight glycoprotein with α2 electrophoretic mobility (SP1α) which is immunochemically identifiable with pregnancy-specific β1 glycoprotein (SP1β). Serum samples from 47 volunteers in the 3rd trimester of pregnancy were subjected to measurements of pregnancy specific β1 glycoprotein in rocket immunoelectrophoresis, quantitative crossed-immunoelectrophoresis and radioimmunoassay. Rocket immunoelectrophoresis gives a result which reflects the total SP1 content, i.e. SP1α and SP1β while quantitative crossed-immunoelectrophoresis permits differentiation between the two molecules. Radioimmunoassay predominantly measures authenic SP1, i.e. SP1β in the presence of physiological amounts of SP1α.

The Value of Measurement of Pregnancy-Specific Proteins in Twin Pregnancies

In this study of 53 twin pregnancies, the plasma concentrations of the placental proteins, placental lactogen (hPL), and pregnancy-specific glycoprotein (SP1) were measured. Placental lactogen was found to be of more value than SP1 both in the detection of twins and in assessment of fetal growth. Serial measurement of either protein would seem to be more useful in assessment of fetal growth than single measurements. Preliminary studies of the less well known placental protein, PP5, in a small series of twin pregnancies indicate that it may also prove to be of clinical value in the detection and monitoring of twin pregnancies.

Placental secretion of oestrogens and protein hormones.

In order to trace the passage of steroids and proteins from the placenta to the maternal peripheral blood, samples of retroplacental blood, uterine vein blood and peripheral blood were taken from women undergoing Caesarean section at term. The concentration of unconjugated oestriol, total oestriol, human placental lactogen and pregnancy specific beta1 glycoprotein was measured. The oestrogen concentration in the uterine vein was higher than the peripheral blood, the placental lactogen was slightly higher and the pregnancy specific beta1 glycoprotein was the same in the uterine vein and the peripheral veins. In keeping with this, the retroplacental blood had a high concentration of oestrogen, moderately raised placental lactogen and a low pregnancy specific glycoprotein concentration. It is concluded that there is a rapid secretion of oestriol from placenta to the mother; a slower secretion of placental lactogen and no clear evidence of a flow of pregnancy specific glycoprotein from the placenta.