International Society of Blood Transfusion Working Party on Terminology for Red Cell Surface Antigens.
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Biomedical subjects
Publications and source records attributed to L Kornstad.
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BACKGROUND: Antigens of the MNS blood group system are located on two sialoglycoproteins, GPA and GPB, encoded by GYPA and GYPB. The molecular backgrounds of the low-frequency antigens Ny(a) and Os(a) are not known. STUDY DESIGN AND METHODS: Immunoblotting and a monoclonal antibody-specific immobilization of erythrocyte antigens (MAIEA) assay were used to analyze Os(a). PCR-amplified products of the coding exons of GYPA were studied by single-strand conformation polymorphism analysis, and exon 3 was sequenced. Synthetic peptides were used in hemagglutination-inhibition tests. RESULTS: Sequencing of GYPA exon 3 of two unrelated Ny(a+) persons revealed heterozygosity for a T194A base change encoding an Asp27Glu substitution. Immunoblotting with anti-Os(a) and an MAIEA assay with MoAbs to GPA showed that Os(a) is on GPA. Sequencing exon 3 of an Os(a+) person from the only family with Os(a) revealed heterozygosity for a C273T base change encoding a Pro54Ser substitution. A synthetic peptide representing part of GPA with the Os(a) mutation (VRTVYPSEEETGE) completely inhibited anti-Os(a), whereas the control peptide (VRTVYPPEEETGE) did not inhibit anti-Os(a). CONCLUSION: Ny(a) and Os(a) are low-frequency antigens of the MNS blood group system that represent Asp27Glu and Pro54Ser substitutions in GPA, respectively.
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Blood samples from 15,426 blood donors from 17 out of Norway's 19 counties were tested for the presence of Kell (k) antigen. The K+ frequency in the total series was 8.28%, ranging from 4.61% in East-Agder county to 10.36% in Sogn and Fjordane. A1A2BO grouping of the donors showed that the lowest frequencies of group O were found in southeastern Norway (the counties surrounding the Oslo Fjord), and the highest along the coast of western Norway and in Nordland county. The highest A2 blood group frequencies were found in the three counties of northern Norway, with a maximum value in Finnmark county. The ratio between the genes determining the A1 and A2 properties (the p1/p2 ratio) was highest in southern Norway where in most counties was above 3. All the counties along the coast from Sogn and Fjordane northwards to the northern end of the country gave p1/p2 ratio below 3 and, in Finnmark, it was slightly below 2.
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Testing of Ls(a+) and Rl(a+) red cells with numerous antisera containing antibodies to low-incidence antigens indicated that these antigens are identical. This conclusion was confirmed by adsorption and elution tests, and supported by immunoblotting of Ls(a+) and Rl(a+) cells with antibodies to glycophorin C and glycophorin D.
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Scanning immune electron microscopy using a monoclonal anti-A antibody which reacts with all type A oligosaccharide chains revealed A antigens on less than 5% of Am and Ael cells, some of which showed extremely strong labelling. This explains why Am and Ael cells can absorb significant amounts of anti-A without being agglutinated. A3 may be a heterogeneous subgroup, since A antigens were found on 82 and 58%, respectively, of the cells of 2 A3 individuals. A antigens were found on 75% or more of Ax cells. In many weak A individuals A-positive cells are apparently best detected if an anti-A is used which reacts strongly with other A oligosaccharide chains than type 2. From hyperimmune pregnancy sera Ax, Am and Ael erythrocytes absorbed antibodies which seemed to have other fine specificities than those absorbed by A2 cells. We conclude that weak subgroups of A may deviate from A2 both by number of erythrocytes expressing A antigens and the biochemical nature of the antigens.
At the 14th Nordic Congress on Transfusion Medicine, held in Reykjavik in 1993, it was recommended that every blood bank should have an established programme for the management of screening-positive donors and blood components deriving from them. Other topics discussed at the congress were the education of registrars in transfusion medicine, new screening methods and questions of quality assurance.
A programme for external quality control in blood group serology has been run in Norway since 1983 by the National Institute of Public Health. Uncomplicated AB0 and Rh(D) grouping, including Du typing, has been performed satisfactorily. Rh(D) grouping of presensitized, Rh (D) negative cells is still a problem, but one which has been reduced significantly. Both indirect and direct antiglobulin reactions have given about 15% false negative results, mainly with weak antibodies and weakly sensitized cells. Poor training of technicians in reading weak agglutination reactions may be an important source of error. The importance of post-graduate training of blood bank staff is emphasized.
Survivors from meningococcal disease (serogroups B and C) and a control series (blood donors) were examined for their ability to secrete ABH blood group substance. The examination was done indirectly by determining their Lewis phenotypes. There was no significant difference in the secretor status between the two groups.
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 proposita was classified as B(el), B(y), or B(m), Le(b+) by routine blood grouping and by adsorption/elution studies using anti-A and -B hyperimmune pregnancy sera. Red cells from the proposita adsorbed as much anti-B from the hyperimmune sera as did red cells from normal B individuals, but adsorbed less anti-A,B (group O serum). Saliva contained H, but not B, soluble substance. Red cells from the proposita and a normal B donor were sensitized with monoclonal A and B blood group antibodies immunolabeled with colloidal gold particles, and examined in a scanning electron microscope. B antigens were found on more than 95 percent of normal B cells, but on only 2-3 percent of red cells from the proposita. However, when the same cells were sensitized with anti-A,B that reacted strongly with B oligosaccharides other than type 2 chains, half of the labeled red cells from the proposita were labeled more strongly than any normal B cells. Our results explain why red cells from the proposita adsorb significant amounts of anti-B and anti-A,B without being agglutinated by these antibodies. The results of both adsorption/elution and immunolabeling suggest that the B antigen on her cells differs biochemically from that on normal B cells.
A central issue at the 13th Scandinavian Congress on Blood Transfusion Medicine was national self-sufficiency in plasma and plasma products, as outlined in the resolution adopted by the Council of Europe in 1990. Delegates also discussed the serological screening of donors to prevent the transmission of infection, new developments in the production of blood components, leukocyte filtration and serological technology.
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A significant fraction (30%) of the genetically determined variance in plasma concentration of the von Willebrand factor antigen (vWf:Ag) has been shown to be related to ABH determinants. Individuals with blood group O, who have the highest amounts of blood group H substance, have the lowest concentration of vWf:Ag. The Lewis substances, Le(a) and Le(b), are biochemically closely related to the ABH substances as both can be produced from the same precursor substance. We studied the effect of the presence of the Lewis antigens on the plasma concentration of vWf:Ag and factor VIII antigen (VIII:Ag) in 323 individuals of different ABO groups from a series of twins and in 58 blood donors of blood group O. Among persons belonging to blood group O, those with the Le(a) antigen had a higher concentration of both vWf:Ag and VIII:Ag than individuals lacking Le(a). Le(a+b-) people are nonsecretors and Le(a-b+) people are secretors of ABH substance. Thus, the lowest concentration of vWf:Ag and VIII:Ag was found in group O secretors. The effect is most likely due to an effect of the secretor locus. This finding may be of importance for the detection of carriers of hemophilia A and for the diagnosis of type I von Willebrand disease.
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