Biomedical subjects
Publications and source records attributed to M Moulds.
Concordance of reactions of Wu+ and 'Hov'+ cells with 153 sera containing multiple specificities to low-incidence antigens indicates that the 'two' antigens are identical. This conclusion is confirmed by absorption and elution studies.
The Glycophorins (GPs = sialoglycoproteins) in erythrocyte membranes from various Black individuals, some of which exhibit the M1, Can, Sj, Tm, Sext and/or Hu antigens, and several Caucasian donors, including pooled fetal red cells, were studied. Using agglutination inhibition assays with GP fractions, GP fragments and chemically modified GPs as well as trypsin treatment of intact red cells, the antigens defined by anti-M1, anti-M+M1, anti-Can and anti-Tm sera were found to be located on the N-terminal tryptic peptide (T2, residues 1-31) of the major GP (GP A = MN sialoglycoprotein). Evidence was obtained that the N-terminal amino-acid residue, NeuNAc and/or (a) different sugar residue(s) are involved in the antigens. Amino-acid sequence and composition analyses excluded an amino-acid exchange within the N-terminal region (residues 1-31) of GP A. Carbohydrate analyses revealed the attachment of GlcNAc residues (up to about five, dependent on the strength of the above-mentioned antigens) to O-glycosidically linked oligosaccharides within the N-terminal portion (residues 1-31) of GP A. As judged from the carbohydrate compositions of peptides, the alteration of the O-glycosidic oligosaccharides is associated with a slight increase of the Gal and Fuc contents and a slight decrease of the NeuNAc level. Analyses of small, secondary cyanogen bromide and V8 proteinase peptides from the N-terminal region of GP A from Blacks, Caucasians and Caucasian fetal cells suggest that the variable attachment of small quantities of GlcNAc (about 0.03 to about 0.2 residues per peptide molecule) accounts, at least in part, for the polymorphisms detected by anti-Can and the original anti-Tm (serum Sheerin). Remarkably, the GlcNAc-containing O-glycosidic oligosaccharides occur only in small quantities, or not all at, within the positions 32-61 of GP A and the glycosylated domains of GP B and GP C.(ABSTRACT TRUNCATED AT 400 WORDS)
DNA from a series of families segregating for Aub was analyzed with a genomic DNA probe which defines a Bg1 I polymorphism for apolipoprotein C II (APOC2). The investigation revealed that the gene for Aub is closely linked to APOC2 (z = 8.43 at theta = 0.00) for paternal and maternal meioses combined, to LW (z = 3.61 at theta = 0.00) in paternal meioses and less closely linked to SE (z = 3.10 at theta = 0.09) for combined paternal and maternal meioses. Therefore, we propose a chromosome 19 location for the Aub gene.
A multilaboratory investigation during several years has identified a low incidence antigen JAL on the red cells of 7 propositi. JAL appears to be associated with two unusual Rh complexes, one of which produces a depressed C antigen and the other a depressed c antigen. Family studies strongly suggest that the JAL antigen is encoded by the RH locus. Anti-JAL has been implicated in haemolytic disease of the newborn and is thus considered to be a clinically significant antibody.
Anti-Au, the first example of the antithetical antibody to anti-Au, was identified in the serum of a blood donor who had been transfused 16 years previously. Au has a gene frequency of 0.4326 in an American black population and 0.2994 in a southern English donor population. The expression of Au is suppressed by In(Lu). XS2 also suppresses Auberger antigen expression.
Three examples of an antibody were found to be detecting a red cell polymorphism probably identical to MER2. The antibodies were made by Jews originating from India and living in Israel. Two of them were sibs and the third was unrelated. All 3 had kidney disease requiring renal dialysis and regular blood transfusion. In 2 cases the antibodies were detected before dialysis was started and before the patients had been transfused. The human antibodies reacted with red cells of 90% of Israeli blood donors tested. In tests on selected blood donors, 82 English and 56 Israeli, one of the human antibodies gave almost identical reactions to those given by monoclonal anti-MER2. Anomalous reactions were probably due to anti-Bga. Two of the human antibodies completely blocked, and one partially blocked, the reaction of monoclonal anti-MER2 with MER2+ red cells.
Red cells (RBC) possessing the low-frequency MNSs antigen Dantu from 36 Black individuals (21 propositi) were found to exhibit the NE variety of this phenotype, as judged from the electrophoretic glycophorin (GP) pattern, described in an accompanying article, and/or from the polybrene test which detects the decreased NeuAc level of these RBC. All known DantuNE RBC (53) exhibit the phenotype M+N+. This finding as well as family studies and immunochemical investigations demonstrate that the DantuNE allele encodes a blood group M-specific GP A. Thus, the strongly decreased GP A level of RBC from DantuNE heterozygotes represents the product of the Dantu allele and its normal counterpart. It is suggested that the formation of a complex with the anion channel protein (band 3) represents the prerequisite for optimum incorporation of GP A into normal RBC membranes. The hybrid GP in DantuNE RBC, produced in large quantity, might suppress the incorporation of GP A in a cis and trans manner via the formation of a complex with band 3. The hybrid GP in DantuNE RBC lacks U activity, but expresses N activity and a qualitatively altered s antigen, thus proving its GP B-GP A hybrid nature in conjunction with data described in the accompanying article. Screening of ficin-treated RBC with Vicia lectin revealed that the Dantu phenotype exhibits a frequency of about 0.005 in American Blacks and less than 0.001 in Germans.
For some time, anomalous serological reactions have been observed when the same anti-Swa sera are tested against red cells from different individuals reported as Sw(a+). A comparative collaborative study using the same collection of Sw(a+) cells and anti-Swa sera was undertaken by 4 reference laboratories, and it was found that Swa represents a heterogeneous group of antigens that can be subdivided into two categories. Both categories, Sw(a+) 700:41 and Sw(a+) 700:-41, were shown to be inherited.
Allo-anti-Chido (Ch) was detected in a patient whose red cells typed as Ch+. The C4 allotype of the patient was A4,B2 which associates strongly with the Ch phenotype Ch:1,-2,3,4,-5,6. Anti-Ch2 + Ch5 were the Ch specificities identified. Absence of only Ch2 and Ch5 determinants on the C4B protein allowed this unique immune response to blood transfusion.
The sialoglycoproteins (glycophorins) in human red cell membranes of rare individuals lacking totally (Ge-1,-2,-3 phenotype) or partially (Ge-1,-2,3 phenotype) the Gerbich (Ge) blood group antigens and two Ge-1,-2,-3 heterozygotes were studied by dodecylsulfate polyacrylamide gel electrophoretic techniques. Two sialoglycoproteins (components D and E) were not detectable in the membranes from the homozygotes and found to be decreased by about 50% in those from the heterozygotes. Ge--1,-2,-3 and Ge-1,-2,3 cells were found to contain a 'new' component (mol. masses about 29 and 30 kDa, respectively) possibly representing a D/E hybrid molecule. This sialoglycoprotein was not detectable in membranes from the Ge-1,-2,-3 heterozygotes, suggesting that the Ge-1,-2,-3 phenotype may be caused by at least two different alleles at the Ge blood group antigen locus. Hemagglutination or hemagglutination inhibition tests involving anti-Ge 1,2,3 and -Ge 1,2 as well as native and enzyme-treated normal red cells (phenotype Ge 1,2,3) or membrane and sialoglycoprotein fractions from normal erythrocytes indicate that the receptors of these sera are located within the glycosylated domain(s) of the D and/or E sialoglycoprotein(s). Our data suggest that the Ge locus encodes the polypeptide sequences of the D and E sialoglycoproteins.
A survey of sera containing antibodies to multiple low-incidence antigens revealed a variety of patterns of reactions with NFLD+, BOW+, and Wu+ red cell samples. Although NFLD, BOW, and Wu are distinct antigenic determinants (International Society of Blood Transfusion numbers 700.37, 700.46, and 700.13, respectively), their ability to absorb and elute "crossreactive" antibodies indicates a serologic and possibly a genetic relationship among the three.