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Background The D typing strategies in several European countries protect carriers of D category VI ( DVI) from anti- D immunization but not carriers of other partial D. Besides DVI, one of the clinically most important partial D is D category IV ( DIV). A detailed description and direct comparison of the different DIV types was missing. Study Design and Methods RHD nucleotide sequences were determined from genomic DNA. D epitope patterns were established with commercial monoclonal anti- D panels. Results DIV comprises several variants of the D antigen with distinct serology, molecular structures, evolutionary origins, and ethnic prevalences. The DIV phenotype is determined by 350 H shared by all, but not limited to, DIV variants which are further divided into DIVa and DIVb. The DIVa phenotype is expressed by DIV Type 1.0 harboring 350 H and the dispersed amino acids 62 F, 137 V, and 152 T. The DIVb phenotype is expressed by DIV Type 3 to Type 5 representing RHD-CE-D hybrids. Four of the six postulated DIV variants were encountered among 23 DIV samples analyzed. Of 12 DIV carriers with anti- D, 10 were female and seven likely immunized by pregnancy. Two DIV-related alleles are newly described: DWN, which differs from DIV Type 4 by 350 D and epitope pattern. DNT carries 152 T, known to cause a large D antigen density. Conclusion DIV alleles arose from at least two independent evolutionary events. DIV Type 1.0 with DIVa phenotype belongs to the oldest extant human RHD alleles. DIV Type 2 to Type 5 with DIVb phenotype arose from more recent gene conversions. Anti- D immunization, especially dreaded in pregnancies, will be avoided not only in carriers of DVI but also in carriers of other D variants like DIV, if our proposed D typing strategy is adopted. [ABSTRACT FROM AUTHOR]

BACKGROUND: MER2 (RAPH1), the only antigen of the RAPH blood group system, is located on the tetraspanin CD151. Only four examples of alloanti-MER2 are known. We report here two new examples of alloanti-MER2, in women of Pakistani and Turkish origin, one of whom showed signs of a hemolytic transfusion reaction (HTR) after transfusion of 3 units of red cells (RBCs). STUDY DESIGN AND METHODS: Standard serologic methods were used. A monocyte monolayer assay (MMA) was used to assess the potential clinical significance of one of the antibodies. All exons and flanking intronic sequences of CD151 were amplified and sequenced. A homology model for CD151 second extracellular loop (EC2) was constructed based on the crystal structure of CD81. RESULTS: RBCs of both patients did not react with alloanti-MER2, and neither of their antibodies reacted with MER2-negative RBCs. The MMA results suggested that the antibody that appeared to have caused an HTR had the potential to be clinically significant. Both patients were homozygous for a 511C>T mutation in CD151 encoding an Arg171Cys change. This change did not result in any significant structural rearrangement in the protein model. CONCLUSIONS: Two MER2-negative patients with anti-MER2 are homozygous for the same novel mutation encoding an amino acid substitution in the EC2 of CD151. One of the antibodies may have been responsible for an HTR, and crossmatch-compatible RBCs should be recommended for transfusion to patients with anti-MER2. [ABSTRACT FROM AUTHOR]

The hybrid glycophorin in Dantu-positive human erythrocytes of the N. E. variety was not cleaved by treatment of intact cells with various proteases, in contrast to normal glycophorins. Therefore, it could be purified by phenol/saline extraction of membranes from trypsin-treated and chymotrypsin-treated red cells and subsequent gel filtration in the presence of Ammonyx-LO. The complete structure of the hybrid molecule, comprising 99 amino acid residues, was elucidated by sequence analyses of peptides prepared by chymotrypsin, trypsin, cyanogen bromide or V8 proteinase treatment. The N-terminal 39 residues and the glycosylation of the molecule were found to be indistinguishable from those of blood-group-s-specific glycophorin B. Conversely, the residues 39- 99 were shown to be identical with the residues 71 - 131 of the major blood-group M-active or N-active sialoglycoprotein (glycophorin A). Hemagglutination inhibition assays revealed that the Dantu antigen represents a labile structure. The receptor might be located within the residues approximately 28-40 of the hybrid glycophorin, as judged from the effects of modifications of membranes. Our data provide an explanation for the previous findings that Dantu-positive cells (N. E. type) exhibit a protease-resistant N antigen and a qualitatively altered s antigen. [ABSTRACT FROM AUTHOR]

The major human erythrocyte membrane sialoglycoprotein (glycophorin A or MN glycoprotein) was purified from the red blood cells of an individual, homozygous for the Mi-VII gene in the Miltenberger subsystem of the MNSs blood-group system. The complete structure of a tryptic peptide comprising the residues 40-61 of glycophorin A was deduced from manual sequence analyses. The Mi-VII-specific glycophorin A was shown to exhibit an arginine → threonine and a tyrosine → serine exchange at the positions 49 and 52 respectively. The threonine-49 residue was found to be glycosylated. Inhibition assays demonstrated that one of the Mi-VII-specific antigen determinants (Anek) is located within the residues 40-61 of glycophorin A and comprises sialic acid residue(s) attached to O-glycosidically linked oligosaccharide(s). Our data contribute to an understanding of the Miltenberger system and provide an explanation at the molecular level for the previous finding that the erythrocytes from the Mi-VII homozygote lack a high-frequency antigen (EnaKT), located within the residues 46-56 of normal glycophorin A. [ABSTRACT FROM AUTHOR]

The N-terminal structures of the MN and Ss erythrocyte membrane sialoglycoproteins (glycophorins A, B) from two Henshaw (He) blood-group heterozygotes were determined by manual sequencing of tryptic glycopeptides and various secondary fragments. No structural alteration of the MN glycoprotein could be detected. The He-specific portion of the Ss glycoprotein was found to exhibit the N-terminal sequence Trp-...-...-...-Gly- (+ =glycosylation). Thus it differs at three positions from its normal counterpart which possesses 'N' activity and exhibits the N-terminal structure Leu-...-...-...-Glu-. Analysis of the Ss glycoprotein from 15 He-negative erythrocyte samples did not reveal any of the three He-specific structural alterations. The presence of a glycine residue at the fifth position of the blood-group-M-active MN glycoprotein as well as in the He-specific Ss glycoprotein provides an explanation for the occurrence of antisera (anti-Me) reacting with the M and He antigens. [ABSTRACT FROM AUTHOR]