Three Pregnancy-Associated Human Plasma Proteins: Purification, Monospecific Antisera and Immunological Identification

Abstract

Three human pregnancy-associated plasma proteins (PAPPs), which were detected only during pregnancy with appropriately absorbed antisera to pregnancy plasma, were purified from third trimester plasma. The authors employed combinations of sequential DEAE-cellulose and hydroxylapatite chromatography; Sephadex G-100, G-200 and Sepharose 6B gel filtration; isoelectric focusing; and/or ammonium sulfate salting out. Each final product was shown to contain only one PAPP, to be immunologically free of most normal plasma proteins, and to have specific activities 100- to 145-fold greater than in the original pregnancy plasma. Rabbits immunized with these preparations responded with antisera which became mono-specific to their respective PAPP after appropriate absorption. PAPP-D, the one with low molecular weight (20,000), was shown immunologically to represent human placental lactogen. Another, PAPP-C, has been found to be identical to the pregnancy-specific β₁-glycoprotein described by Bohn (designated by him as SP₁ protein). The other, PAPP-A, of molecular weight 750,000, is distinct from the other two pregnancy-associated proteins of Bohn (designated SP₂ and SP₃), as well as the α₂-pregnoglobulin of Berne. Since the latter and SP₃ proved to be identical immunologically, and since it has been reported that SP₃, Xh factor, pregnancy-associated globulin (PAG or Pal), and the pregnancyzone proteins are identical to each other, PAPP-A may represent a new pregnancy-specific protein. None of the PAPPs were detected in sera from 102 patients with various malignancies.

Measurement of Pregnancy-Associated Plasma Proteins during Human Gestation

“…The four pregnancy protein immune systems in the crossed antibody immunoelectrophoresis had been identified earlier in tests with the purified PAPP's (2,3). In the present study, the precipitin hills were readily identified on the basis of their electrophoretic mobilities, their times of appearance, and the characteristics of the precipitin lines.…”

“…In fact, Bohn has recently preferred to designate them as acute phase proteins (35). In contrast, all of the PAPP's described here appear to be generally pregnancy specific, since none of them have been detected by the methods used in nonpregnant normal male or female plasma, in plasma from patients with a variety of cancers not derived from the trophoblast, or in women receiving hormonal contraceptives (3).…”

“…Three of them were partially purified and were used in the production of monoReceived for publication 22 January 1274 and in revised form 24 April 1974. 'Abbreviations used in this paper: HCG, human chorionic gonadotropin; HPL, human placental lactogen; PAPP, pregnancy-associated protein; RIA, radioimmunoassay; SP1, 2,3, pregnancy-associated proteins described by Bohn (18). specific antisera (3). Analogous PAPP's were also found in the rat and mouse, although there was little or no immunological relationship between these proteins of the three species (4).…”

“…One of the PAPP's (PAPP-D) has recently been identified immunologically as human placental lactogen (3,22), while another (PAPP-C) was shown to be identical to the pregnancy-specific 91-glycoprotein (SP1) described by Bohn (3,18). PAPP-A may represent a heretofore undescribed PAPP, based on published data and on observations obtained in our laboratory showing that it was unrelated immunologically to Bohn's pregnancy-associated proteins, SP2 and SP3, and to Berne's a2-pregnoglobulin (18,20,23).…”

Association of low levels of first trimester Pregnancy Associated Plasma Protein (PAPP-A) with adverse pregnancy outcomes: An observational study

“…Pregnancy Associated Plasma Protein (PAPP-A) is an important glycoprotein found in maternal blood that increases as pregnancy progresses [1], although it is not specific to pregnancy [2,3]. In pregnancy, PAPP-A is principally expressed in the syncytiotrophoblast of the placenta, which forms the main source of circulating maternal PAPP-A [4][5][6].…”