An Enzymatic Marker in Mothers of Trisomy 21 Children: Neutrophil Alkaline Phosphatase

Abstract

Neutrophil alkaline phosphatase (NAP) from 12 mothers of normal children was investigated and the results compared to those of 7 mothers with trisomy 21 offsprings, in an attempt to determine a parental molecular change in this chromosomal abnormality. The biochemical properties of the enzyme were analyzed by the procedures of isoenzyme characterization, i.e. enzyme assays, thermostability, inhibition patterns and slab gel electrophoresis. Immunological properties were determined on 5 samples from normal mothers and on the same sample number of mothers with affected children. In these latter NAP showed characteristics that were to some extent different from the ones of normal controls. The following changes were observed: highly significant loading of membrane and nucleus pellets in NAP activity, poor effect of inhibitors on thermostable component and immunodepletion measured by a significant decrease of the normal affinity for antiliver and antiplacental alkaline phosphatase antisera. These findings are discussed in the light of our knowledge of alkaline phosphatase isoenzymes.

Heat stable and urea resistant alkaline phosphatase in maternal neutrophils from normal and Down syndrome pregnancies

“…Some previous studies confirmed, in cases of affected fetuses, a placental-like NAP activity distinct from that of control pregnant mothers. A greater proportion of activity along with an altered iso-electric focusing pattern and anomalous responses to some specific inhibitors were demonstrated in trisomy 21 affected pregnancies (Grozdea et al, 1983Vergnes et al, 1988;Brisson-Lougarre et al, 1991;Denier et al, 1996). In other reports no meaningful differences were elucidated (Aitken et al, 1996).…”

“…PAP is synthesized in the syncytiotrophoblast and reaches the maternal circulation early in the first trimester (Okamoto et al, 1990). An association between elevated activity of neutrophil PAP and trisomy 21 was reported in affected individuals (Lennox et al, 1962;Tangheroni et al, 1971;Grozdea et al, 1991), as well as in mothers with presently ongoing or previous Down syndrome pregnancies (Grozdea et al, 1983;Vergnes et al, 1988;Grozdea et al, 1988;Brisson-Lougarre et al, 1991;Denier et al, 1996). An increase in PAP activity was also described in maternal serum in the second trimester of affected pregnancies (Ind et al, 1994;Denier et al, 1996).…”

Changes in Immunological Properties of Neutrophil Alkaline Phosphatase in Trisomy 21 Pregnancies

“…In normal pregnant women, we found that NAP is sensitive to: L-homoarginine, 3.5 M urea and 56°C heat treatments and insensitive to L-phenylalanine, like liver/bone AP isoenzymes. In trisomy 21 pregnancies, NAP is thermostable at 56 and 65°C, significantly resis tant to 3.5 M urea treatment and insensitive to L-homoarginine, EDTA, and L-phenylalanine [17,18]. Isoelectric focusing clearly confirms that the NAP pattern in women with trisomy 21 pregnancies is different from normal NAP, suggesting the presence of more than one AP isoen zyme: a thermolabile and a thermostable one [9].…”