Abnormal TGFβ levels in the amniotic fluid of down syndrome pregnancies

PROBLEM: The status of cytokines in amniotic fluid (AF) from chromosomally abnormal pregnancy is largely undefined. TGF beta plays a key role in fetal growth and differentiation and is responsible for the immunoregulatory activity of AF in normal pregnancy, but its status in Down syndrome (DS) pregnancies is unknown. In addition we investigated the IL-2 status of AF from DS pregnancies. METHOD OF STUDY: Midtrimester AF from chromosomally normal (n = 25) and abnormal pregnancies with DS (n = 15) were assayed for bioactive and latent TGF beta levels using the mink lung epithelial cell growth inhibition bioassay and for IL-2 activity by the CTLL-2 cell proliferation bioassay and by ELISA. RESULTS: Levels of bioactive TGF beta (mean 4.6 +/- 0.6 U/mL) were significantly increased in DS AF compared with the normal samples (mean 2.8 +/- 0.3 U/mL, P < 0.003) but latent TGF beta levels did not differ between DS and normal groups. In addition DS AFs showed reduced IL-2 like bioactivity compared with normal samples (P = 0.0006) but IL-2 immunoactivity was undetectable in DS and normal AFs by ELISA. CONCLUSIONS: DS AFs display increased TGF beta activity and lacked IL-2 immunoactivity. The reduced ability of DS AFs to stimulate CTLL-2 cell proliferation is unrelated to the IL-2 status of AF. Altered TGF beta levels may prove useful as an additional biochemical index for the detection of DS pregnancies.