AGE-RELATED DEVELOPMENT OF HUMAN ANTI-PIG XENOANTIBODY

Human cytotoxic natural xenoantibodies are believed to be of the immun oglobulin M class in nature, However, a thorough understanding of the development of these natural antixenodonor xenoantibodies remains inco mplete. In this study, serum samples were obtained from newborn, infan t, and adult human beings. An enzyme-linked immunosorbent assay was us ed to determine the binding of human natural immunoglobulin M xenoanti bodies to pig aortic endothelial cells and pig lymphocytes, A compleme nt-mediated cytotoxicity assay was used to measure the cytotoxicity of newborn, infant, and adult serum to cultured pig aortic endothelial c ells and pig lymphocytes. Adult human serum contained both natural imm unoglobulin M and immunoglobulin G xenoantibodies to pig endothelial c ells and lymphocytes, whereas newborn infant serum contained only immu noglobulin G xenoantibodies. Only adult human serum was cytotoxic to p ig endothelial cells and lymphocytes, Human immunoglobulin M xenoantib odies became detectable by age 1 month, By age 2 months these natural anti-pig xenoantibodies reached serum levels equivalent to those In th e human adult and resulted in similar cytotoxicity to that of adult hu man serum, These findings indicate that (1) natural anti-pig immunoglo bulin M xenoantibodies are absent from newborn infant human serum, (2) newborn human serum is not cytotoxic to pig endothelial cells and lym phocytes despite the presence of immunoglobulin G xenoantibodies that bind to pig endothelial cells and lymphocytes, and (3) natural anti-pi g immunoglobulin M xenoantibodies begin to develop as early as age 1 m onth and by age 2 months attain a circulating level comparable to that found in the adult.