Family studies of a human serum isoantigen system (Australia antigen).

RECENTLY, we described what appeared to be a "new" serum protein (Blumberg, 1964; Blumberg et al., 1965). It had been detected using isoprecipitins found in the sera of hemophilia patients who had received large numbers of transfusions. These isoprecipitins reacted, in double diffusion agar gel experiments, with an antigen in the serum and plasma of some normal and diseased individuals. Because the antigen was originally found in the serum of an Australian aborigine, the protein was referred to as "Australia antigen." Preliminary biochemical and immunological studies indicate that Australia antigen contains lipid with electrophoretic mobility and other characteristics similar to those of low density (or beta) lipoprotein. It can, however, be readily distinguished from other lipoproteins by differences in its flotation characteristics, staining properties, and immunological reactions (Alter and Blumberg, 1966) and from the lipoprotein isoantigen system previously reported from this laboratory (Blumberg et al., 1962). Australia antigen was also found to have an unusual population distribution, which probably accounts for the failure to identify this serum protein earlier. The isoprecipitin did not react with sera from normal U. S. white and Negro populations and only rarely (1/1000) with sera from the several northern European populations studied. It was more common (approximately 1%) in Mediterranean populations and even more so in sera collected in the East (approximately 6%: Blumberg et al., 1965, and Table 2). It was also found in relatively high frequencies in patients with leukemia, mongolism (Down's syndrome), and thalassemia, but not in patients with solid tumors or a variety of other diseases (Blumberg and Alter, 1965; Blumberg, 1966). The original populations studied included some sera collected from families. In one of these (Fig. 4 of Blumberg et al., 1965), an extensive pedigree from a Samaritan family of Israel, two sibs were found to have the trait. Studies in other populations (i.e., Marshall Islanders and Cashinahua Indians from Peru) also suggested a familial aggregation, and it became apparent that a systematic family study should be done. Because of the odd distribution of the trait, that is, its extreme rarity in U. S. populations, extensive family studies could not be