Invasive Trophoblast Antigen (Hyperglycosylated Human Chorionic Gonadotropin) as a First-Trimester Serum Marker for Down Syndrome

Abstract

Hyperglycosylated human chorionic gonadotropin (hCG) is a variant of hCG with more asparagine (N)-linked triantennary carbohydrates and a serine (O)-linked tetrasaccharide core structure in the β-subunit of hCG (1). Whereas nonhyperglycosylated hCG is secreted by differentiated syncytiotrophoblast cells, hyperglycosylated hCG is secreted solely by invasive cytotrophoblast cells and is therefore also called invasive trophoblast antigen (ITA) (2)(3). Before the sixth week of gestation, ITA appears to be the predominant form of hCG (2)(3)(4). In Down syndrome pregnancies, differentiation of the cytotrophoblast into a syncytiotrophoblast may be delayed, leading to increased production of ITA (5). Urinary ITA is a promising candidate for use as a biochemical marker in Down syndrome screening. In one study conducted during the second trimester of pregnancy, ITA alone detected 78% of the Down syndrome cases at a 5% false-positive rate (6)(7). In a setting that simulated routine use, urinary ITA was reported to be the best single marker in the second trimester (8). In the first trimester of pregnancy, however, the performance of urinary ITA is lower, with a reported 63% Down syndrome detection rate at a 10% false-positive rate (9). ITA is detectable in serum as well as in urine (10). Studies have not been performed with serum ITA because of concerns about the stability of ITA in serum, possible loss of ITA when blood is collected in gel barrier tubes, and possible aggregation. A recently developed automated immunochemiluminometric assay measures ITA in various sample types, including serum (11). In the present study, we investigated the Down syndrome screening performance of serum ITA before 12 weeks of gestation and compared it with the performance of pregnancy-associated plasma protein A (PAPP-A) and free β-subunit in the …