Levels and Molecular Forms of Immunoreactive Trypsin and Chymotrypsin in Amniotic Fluids from Normal and Cystic Fibrosis Fetus

We previously suggested that an activation defect of pancreatic proteolytic zymogens in newborns suffering from cystic fibrosis (CF) might contribute (by an adaptative-like process) to the significant increase of the serum trypsin level observed in the disease at birth. To give support to this hypothesis we studied two pancreatic enzymes: trypsin 1 (IRT) and chymotrypsin A (IRChT) by noncompetitive enzyme immunoassays in amniotic fluids taken at 17-18 weeks of pregnancy. In normal fluids (102), the levels of the two enzymes were widely dispersed between 5 and 100 micrograms/L. A similar pattern was observed for the fluids with a 1 in 4 risk of CF with a normal outcome (24). In contrast, the levels of pancreatic enzymes in the fluids with affected fetus (40) were always below 45 micrograms/L for IRT and 55 micrograms/L for IRChT and most of them were under 20 micrograms/L for both enzymes. The molecular forms of IRT and IRChT in amniotic fluids were studied by gel filtration. In amniotic fluids with affected fetus, a major form of IRT was eluted in a position consistent with the elution of proteins around 25 kDa and two peaks of IRChT were eluted at 75 kDa and 25 kDa. These patterns are similar to those observed in normal serum when zymogens are present and are quite different from the patterns obtained by gel filtration of amniotic fluids with normal outcome.(ABSTRACT TRUNCATED AT 250 WORDS)