ALBERT

Notes: The blood from three individuals belonging to consecutive generations of one family were characterized as cis AB on the basis of (a) the serological behaviour of the B antigen on their red cells, (b) the presence of weak anti-B in their sera and (c) family studies, which unequivocally demonstrated the genotype AB: O for two of the individuals with atypical AB groups.The serological behaviour of the A antigen on the red cells was intermediated between that of normal A1 and A2 cell. The B antigen gave weak and variable reactions with naturally occurring antibodies. Treatment of the cis AB red cells with an α-galactosyltransferase in the serum from an A1B individual rendered them agglutinable by the normal range of anti-B sera, demonstrating that the red cells do not lack precursors for the formation of normal B-active structures.The cis AB sera all contained relatively strong α-N-acetylgalactosaminyl-transferases which had pH optima of 6.0, characteristic of A1 gene-specified enzymes. The affinity of the enzymes for UDP-galactose, as measured by the apparent Ki, appeared to be greater than that of the A transferases in normal A1 and A1B sera. The B-gene transferases in the cis AB sera were very weak and were more readily inhibited by UDP-N-acetylgalactosamine than were the α-galactosyltransferases in normal B and AB sera. Both the A- and B-transferase activities in the cis AB sera are, therefore, in some ways different from the corresponding enzyme activities in the sera of normal A, B or AB donors.Cytogenetic study of blood lymphocytes from all three individuals showed normal karyotypes. Specifically, the terminal bands of the long arms of the No. 9 chromosomes, to which the ABO:Np-1: AK-1 linkage group has been assigned, displayed G bands similar to those in cells from other (normal) individuals examined simultaneously.

Notes: The red cells of a normal male blood donor, K.S., were first grouped as B but he was found to lack anti-A in his serum. Closer investigation revealed that his red cells had very weak A activity, demonstrable only by absorption and elution of anti-A. He is a non-secretor of ABH and a secretor of Lea. Blood group A-, B and H-gene specified glycosyltransferases were detected in his serum. In contrast to the finding of a B antigen of normal strength on his red cells, the B transferase in his serum was only about 30% of the normal level and, despite the very weak A activity of K.S.'s red cells, the A transferase level was about 50% of that found in the serum of group A individuals with normal strength of A antigen. Moreover, the A transferase on the basis of its pH optimum, Km values for donor and acceptor substrates, activation by divalent cations, isoelectric focusing profile and capacity to convert O to A-active cells, was characterized as the product of an A1 gene. A family study showed that K.S.'s wife is group A2 and that they have two sons, one group A2 and the other group B. The group B son is assumed to have inherited a B gene from the propositus but the level of B transferase in the son's serum is three times as high as that in his father's serum. The wife of the propositus and his group A2 son have normal A2 transferases in keeping with their A2 red cell status. The A2 son therefore appears to have inherited an A2 gene from his mother but neither the A1 nor the B gene shown to be carried by his father. The distribution of transferase activities in K.S.'s red cells differs from that in his serum. A level of B transferase within the normal range was found in his red cell membranes but a very low level of A transferase was detected. The discrepancies between the serum transferases and ABO-red cell group, together with the pattern of inheritance within the family, led to a suspicion of chimaerism. This was confirmed by the finding of fibroblasts with the female 46XX karyotype in cultures of the propositus' skin. These results suggest that K.S. is a dispermic chimaera with two different cell lines of the genotypes BO and A1O or A1A1. The group A2 son is assumed to have inherited an O gene from his father. It seems probable that K.S.'s bone marrow and reproductive organs are comprised predominantly of the XY cell line which carries the blood group BO genotype whereas his skin and other tissues which contribute the A1 transferase to his plasma, are partly made up of the XX cell line which carries the blood group A1O or A1A1 genotype.