Lens culinaris agglutinin-reactive alpha-fetoprotein, an alternative variant to alpha-fetoprotein in prenatal screening for Down's syndrome

BACKGROUND: Three serum tests, alpha -fetoprotein (AFP), human chorionic go nadotrophin and unconjugated oestriol, are now widely used for screening fo r Down's syndrome. Lens culinaris agglutinin-reactive alpha -fetoprotein (A FP-L3) is a variant of alpha -fetoprotein with alpha1 -->6 fucose appended to the reducing terminal N-acetylglucosamine. It is the most prominent AFP detected in the serum of patients with hepatocellular carcinoma. METHODS: W e investigated microheterogeneities of the carbohydrate chain on AFP in fet al liver tissues, amniotic fluids and maternal sera obtained from pregnanci es with Down's syndrome using lectin affinity electrophoresis with four lec tins. The percentages of AFP-L3 in maternal sera from 22 Down's syndrome an d 227 unaffected pregnancies were determined. RESULTS: Unlike the case with AFP concentration, the percentage of AFP-L3 in maternal serum and amniotic fluid was similar, and apparantly not influenced by membrane permeability. Knowing the percentage of AFP-L3 in maternal serum was effective for discr iminating between Down's syndrome-affected pregnancies and unaffected pregn ancies. The percentage of AFP-L3 in maternal serum identified 55% of Down's syndrome cases with a 5% false-positive rate. CONCLUSIONS: AFP-L3 should b e an effective replacement for AFP in prenatal Down's syndrome screening.