Age-related development of human anti-pig xenoantibody

Human cytotoxic natural xenoantibodies are believed to be of the immunoglobulin M class in nature. However, a thorough understanding of the development of these natural antixenodonor xenoantibodies remains incomplete. In this study, serum samples were obtained from newborn, infant, and adult human beings. An enzyme-linked immunosorbent assay was used to determine the binding of human natural immunoglobulin M xenoantibodies to pig aortic endothelial cells and pig lymphocytes. A complement-mediated cytotoxicity assay was used to measure the cytotoxicity of newborn, infant, and adult serum to cultured pig aortic endothelial cells and pig lymphocytes. Adult human serum contained both natural immunoglobulin M and immunoglobulin G xenoantibodies to pig endothelial cells and lymphocytes, whereas newborn infant serum contained only immunoglobulin G xenoantibodies. Only adult human serum was cytotoxic to pig endothelial cells and lymphocytes. Human immunoglobulin M xenoantibodies became detectable by age 1 month. By age 2 months these natural anti-pig xenoantibodies reached serum levels equivalent to those in the human adult and resulted in similar cytotoxicity to that of adult human serum. These findings indicate that (1) natural anti-pig immunoglobulin M xenoantibodies are absent from newborn infant human serum, (2) newborn human serum is not cytotoxic to pig endothelial cells and lymphocytes despite the presence of immunoglobulin G xenoantibodies that bind to pig endothelial cells and lymphocytes, and (3) natural anti-pig immunoglobulin M xenoantibodies begin to develop as early as age 1 month and by age 2 months attain a circulating level comparable to that found in the adult.