ONTOGENY OF MEMBRANE COFACTOR PROTEIN - PHENOTYPIC DIVERGENCE IN THE FETAL HEART

Human adult cells are protected from complement-induced damage in part by membrane cofactor protein (MCP, CD46). To examine fetal characteri stics which might influence autoantibody-mediated diseases acquired in utero, such as heart block in neonatal lupus, the tissue expression o f MCP was studied. Using a high ratio of acrylamide: bisacrylamide, im munoblots of tissues from six fetuses (aged 19-24 weeks) probed with r abbit anti-MCP antibodies revealed a band at 60 KD in addition to the known 65 KD and 55 KD isoforms which comprise the codominant allelic s ystem of MCP. Five fetuses expressed the most common MCP polymorphism (predominance of the 65 KD isoform, upper band alpha-phenotype) in the kidney, spleen, liver and lung. In contrast, all hearts from these fi ve fetuses demonstrated a different pattern in which there was a marke d decrease in the intensity of the 65 KD band and accentuation of the lower molecular weight bands. In a sixth fetus, which expressed the se cond most common polymorphism (equal expression of the 65 KD and 55 KD MCP isoforms, alpha beta-phenotype), the heart was similar to the oth er tissues. These studies confirm the expression of MCP in early gesta tional life. Preferential expression of the MCP beta-isoform in the ma jority of fetal hearts irrespective of the phenotype of other organs, suggests tissue-specific RNA splicing or post-translational modificati on which may relate to autoantibody-mediated injury in diseases such a s neonatal lupus.