Heat resistance, immunological and quantitative changes of neutrophil alkaline phosphatase in trisomy 21 pregnancies

Abstract

Neutrophil alkaline phosphatase (NAP) was analysed in 25 pregnant women with trisomy 21 foetuses whose chromosomal aberration was recognized by cytogenetic study after amniocentesis. Enzyme investigation was performed at 20-22 weeks of gestation using cytochemical and biochemical techniques. Twenty-nine women at the same stage of normal pregnancies were selected as controls. In parallel, each mother was karyotyped. Ten subjects from each series underwent biochemical and immunological investigation: measurement of enzyme levels, thermostability study and immunological tests with alkaline phosphatase isoenzyme antibodies. NAP from pregnant women with trisomy 21 foetuses was characterized by: (1) a lower rate of enzyme activity, (2) a large amount of heat-stable enzyme (T = 56 degrees C for biochemical assays, T = 85 degrees C for cytochemical tests), and (3) a marked loss of liver antigenicity. These findings suggest the presence in trisomy 21 pregnancies of a non-specific alkaline phosphatase isoenzyme which appears as an "enzyme marker" in maternal circulating neutrophils.

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

“…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).…”

Kinetic comparison of tissue non-specific and placental human alkaline phosphatases expressed in baculovirus infected cells: application to screening for Down's syndrome

“…NSAP activity of neutrophils have been reported to increase during pregnancy [ 20 ], and presence of a heat stable AP in neutrophils can be a useful marker for the screening of trisomy 21 fetuses [ 24 ]. We sequenced the neutrophil NSAP phosphatase from trisomy 21 pregnant women and trisomy 21 children but no mutation was detected indicating that the differences in alkaline phosphatase characteristics do not originate from a mutant allele of the non specific alkaline phosphatase gene (unpublished data).…”

“…The characteristics of AP from blood neutrophils of women whose fetuses had trisomy 21 differ from those with normal pregnancies. An elevated AP activity has been reported in affected individuals [ 24 ]. An ectopic expression of PLAP seems to appear since i) AP is more stable to heat and urea denaturation [ 24 - 26 ], ii) AP is more sensitive to inhibitors L-homo-arginine, EDTA, L-phenylalanine, L-p-bromotetramisole and sodium thiophosphate [ 26 , 27 ] and iii) AP is less recognized by anti-NSAP antibodies and shows a reaction with anti-PLAP antibodies [ 28 ].…”

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“…An elevated AP activity has been reported in affected individuals [24]. An ectopic expression of PLAP seems to appear since i) AP is more stable to heat and urea denaturation [24-26], ii) AP is more sensitive to inhibitors L-homo-arginine, EDTA, L-phenylalanine, L-p-bromotetramisole and sodium thiophosphate [26,27] and iii) AP is less recognized by anti-NSAP antibodies and shows a reaction with anti-PLAP antibodies [28]. …”