International Society of Blood Transfusion Committee on terminology for red cell surface antigens: Vancouver Report.
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Blood Group Antigens↗
Biomedical subjects
M E Reid
Publications and source records attributed to M E Reid.
A novel DI*A allele without the Band 3-Memphis mutation in Amazonian Indians.
BACKGROUND AND OBJECTIVES: The blood-group antigens Dia and Dib are carried on erythrocyte band 3 and are defined by a single amino acid substitution at position 854 (Leu for Dia and Pro for Dib). The Band 3-Memphis variant has a point mutation (166A>G) in the SLC4A1 gene, which encodes the amino acid substitution Lys56Glu. Two types of Band 3-Memphis, variants I and II, are distinguished by their susceptibility to covalent labelling with 4,4'-diisothiocyanato-1,2-diphenylethane-2,2'-disulphonic acid (H2DIDS). Memphis II is more readily labelled than Memphis I or normal band 3. It is reported that Memphis II is associated with Dia. In a study designed to determine the frequency of the DI*A/DI*B and 166A>G polymorphisms in different populations in Brazil, we found a new DI*A allele. MATERIALS AND METHODS: We studied DNA samples from 70 Amazonian Indians, 71 individuals of Japanese descent, 93 random Brazilian blood donors and 84 blacks with sickle cell disease. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses were performed on all samples, using MspI for DI*A/DI*B (exon 19) and MnlI for 166A>G (exon 4). Exon 4 and exon 19 from four outliers were sequenced. RESULTS: Among Amazonian Indians, DI*A and 166G mutations both had a high frequency (0.57 and 0.54, respectively). In individuals of Japanese descent, these alleles were moderately frequent (0.07 and 0.19, respectively). We identified a new allele with DI*A and 166A (56Lys) in four Amazonian Indians. CONCLUSIONS: Our results revealed that DI*A does not have a strict association with 166G. They also show the relevance of testing a cohort of different populations.
Alleles↗
Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial.
OBJECTIVE: To present the results (to January 1996, the end of blinded treatment) of the Nutritional Prevention of Cancer (NPC) Trial, a randomized trial of selenium (200 micro g daily) designed to test the hypothesis that selenium supplementation (SS) could reduce the risk of recurrent nonmelanoma skin cancer among 1312 residents of the Eastern USA. MATERIALS AND METHODS: Original secondary analyses of the NPC to 1993 showed striking inverse associations between SS and prostate cancer incidence. A subsequent report revealed that this effect was accentuated among men with the lowest baseline plasma selenium concentrations. The effects of treatment overall and within subgroups of baseline prostate-specific antigen (PSA) and plasma selenium concentrations were examined using incidence rate ratios and Cox proportional hazards models. RESULTS: SS continued to significantly reduce the overall incidence (relative risk and 95% confidence interval) of prostate cancer (0.51, 0.29-0.87). The protective effect of SS appeared to be confined to those with a baseline PSA level of <or= 4 ng/mL (0.35, 0.13-0.87), although the interaction of baseline PSA and treatment was not statistically significant. Participants with baseline plasma selenium concentrations only in the lowest two tertiles (< 123.2 ng/mL) had significant reductions in prostate cancer incidence. A significant interaction between baseline plasma selenium and treatment was detected. CONCLUSION: To the end of the blinded treatment the NPC trial continued to show a significant protective effect of SS on the overall incidence of prostate cancer, although the effect was restricted to those with lower baseline PSA and plasma selenium concentrations.
Biopsy↗
Production of recombinant murine-human chimeric IgM and IgG anti-Js(b) for use in the clinical laboratory.
BACKGROUND: Directly agglutinating MoAbs are more useful than IgG MoAbs of murine origin for typing RBCs from donors and patients. The molecular manipulation and conversion of a murine IgG MoAb into mouse- human chimeric IgM and IgG antibodies are described. STUDY DESIGN AND METHODS: cDNA encoding the variable heavy- and light-chain genes of a murine hybridoma anti-Jsb cell line (MIMA-8) were cloned into human IgM or IgG expression vectors, which were then separately stably transfected into SP2/0-Ag14 B-cells. The secreted antibodies were screened by ELISA and analyzed by flow cytometry and hemagglutination. RESULTS: Forty percent (16 of 40) of the stable clones secreted IgM and 66 percent (12 of 18) of the stable clones secreted IgG. The chimeric IgM from the highest expressing clone reacted 4+ in LISS at room temperature. The chimeric IgG from one clone reacted 4+ by the IAT, resembling the specificity of the original murine antibody. Both manipulated MoAbs reacted specifically with RBCs as assessed by flow cytometry. CONCLUSION: Human-mouse chimeric IgM and IgG from a murine IgG MoAb anti-Jsb has been successfully engineered for use in the clinical laboratory. This approach can potentially be used to manipulate other murine MoAbs to blood group antigens into more clinically useful human isotypes.
Animals↗
Section 3: Epitope determination of monoclonal antibodies to glycophorin A and glycophorin B. Coordinator's report. Antibodies to antigens located on glycophorins and band 3.
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Amino Acid Sequence↗
Characterization of a Plasmodium falciparum erythrocyte-binding protein paralogous to EBA-175.
A member of a Plasmodium receptor family for erythrocyte invasion was identified on chromosome 13 from the Plasmodium falciparum genome sequence of the Sanger Centre (Cambridge, U.K.). The protein (named BAEBL) has homology to EBA-175, a P. falciparum receptor that binds specifically to sialic acid and the peptide backbone of glycophorin A on erythrocytes. Both EBA-175 and BAEBL localize to the micronemes, organelles at the invasive ends of the parasites that contain other members of the family. Like EBA-175, the erythrocyte receptor for BAEBL is destroyed by neuraminidase and trypsin, indicating that the erythrocyte receptor is a sialoglycoprotein. Its specificity, however, differs from that of EBA-175 in that BAEBL can bind to erythrocytes that lack glycophorin A, the receptor for EBA-175. It has reduced binding to erythrocytes with the Gerbich mutation found in another erythrocyte, sialoglycoprotein (glycophorin C/D). The interest in BAEBL's reduced binding to Gerbich erythrocytes derives from the high frequency of the Gerbich phenotype in some regions of Papua New Guinea where P. falciparum is hyperendemic.
Animals↗
A DNA-based immunization protocol to produce monoclonal antibodies to blood group antigens.
A major challenge facing transfusion medicine is the establishment of immunological methods to produce specific and avid blood group typing reagents to the many polymorphic blood group antigens. This is especially true when sources of human antibody are limited. Based on the knowledge that inoculation with plasmid DNA can induce a humoral response in the host animal, we inoculated mice with plasmid DNA followed by a single boost injection with plasmid-transfected cells that have a high level of expression of the same target protein. Using this method, several hybridoma clones that produced strongly reactive antibodies specific for the Kell polymorphic antigens (anti-K, anti-k, anti-Kp(a)) were isolated. The monoclonal antibodies that were produced with this method have potential clinical utility for identifying a patient's blood type and for screening for antigen-negative donor blood.
Animals↗
16Cys encoded by the RHce gene is associated with altered expression of the e antigen and is frequent in the R0 haplotype.
Serological observations have suggested that numerous D, many e (especially in Blacks), several E, and rare c variants exist within the Rh blood group system. The molecular basis for expression of many of these variants has been elucidated. This study describes five unrelated Caucasians whose red blood cells reacted with polyclonal anti-e but did not react with some monoclonal anti-e, which suggested that they carried a variant e antigen. Molecular investigation revealed the presence of a 48G-->C change (encoding cysteine instead of tryptophan at amino acid 16) in their RHce gene. No other differences were found, which suggests that amino acid residues located in the first transmembrane region can affect expression of the e antigen, whose critical residues are on the predicted fourth external loop of the protein. This polymorphism has not previously been observed because polyclonal anti-e does not distinguish this variant from wild type. This position is polymorphic in RHce alleles and the presence of the 48C nucleotide is often found in the R0 (Dce) haplotype.
Antibodies, Monoclonal↗
International Society of Blood Transfusion Working Party on Terminology for Red Cell Surface Antigens.
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Amino Acid Substitution↗
Direct evidence for the existence of Miltenberger antigen.
The Miltenberger (Mi) subsystem, which originally consisted of four phenotypes, now has 11 phenotypes. The antigens of this subsystem belong to the MNS blood group system. The Mia antigen has been reported to be present on red blood cells with several Miltenberger phenotypes, namely: Mi.I, Mi.II, Mi.III, Mi.IV, Mi.VI and Mi.X. However, the existence of the Mia antigen as a separate entity has been in question and difficult to prove with polyclonal reagents. We report the first monoclonal anti-Mia (GAMA210), whose epitope is TNDKHKRD or QTNDMHKR, and thereby confirm the existence of the Mia antigen.
Animals↗
Point mutations in KEL exon 8 determine a high-incidence (RAZ) and a low-incidence (KEL25, VLAN) antigen of the Kell blood group system.
BACKGROUND AND OBJECTIVES: The molecular basis of two Kell blood group antigens, RAZ (provisionally KEL27) and VLAN (KEL25), were determined. MATERIALS AND METHODS: The DNA sequences of the open reading frames and the flanking intron regions of the 19 KEL exons from RAZ and VLAN probands were compared with that of common KEL. Genotyping assays were designed to confirm and detect RAZ and VLAN phenotypes. RESULTS: A homozygous G865A mutation, encoding lysine instead of glutamic acid at amino acid position 249 of Kell protein, defines the RAZ phenotype, while a heterozygous G863A mutation in KEL, encoding an arginine to glutamine substitution at amino acid 248, characterizes the VLAN phenotype. CONCLUSION: Point mutations G865A and G863A, in adjacent codons of KEL exon 8, which cause amino acid substitutions, characterize the RAZ and VLAN Kell blood group phenotypes.
Antigens↗
A MAR-like antibody in a DCWe/DCWe person.
BACKGROUND: MAR (RH51), a high-incidence antigen in the Rh blood group system, is absent from RBCs with a double dose of CW or CX or a single dose each of CW and CX antigens, as well as from rare Rh phenotypes including D- - and Rh(null). The MAR antigen is associated with the presence of Ala36 and Gln41 on the RhCe protein. The original example of anti-MAR, described in 1994, was made by a DCWe/DCXe woman. It was possible that the antibody directed against a high-incidence antigen in the Rh system made by a DCXe/DCXe woman (CM) in 1983 was anti-MAR. CASE REPORT: A 52-year-old, multiply transfused, white woman (CJ) with pre-existing anti-c, -E, and -Jk(a) presented for preoperative work-up for her fifth open heart procedure. The strength of the reaction of her RBCs with anti-CW suggested a double dose of CW antigen. Her serum, which unexpectedly was strongly reactive with c-, E-, Jk(a-) RBCs by PEG indirect antiglobulin test, was incubated with E-c-, Jk(a-) RBCs, and an eluate was prepared. This eluate reacted 3+ with E-c-, Jk(a-) RBCs but did not react with Rh(null) (n = 5), - - (3), DCW- (2), Dc- (1), or DCWe/DCWe (1) RBCs. Two related DCXe/DCXe and two unrelated DCWe/DCXe RBC samples were weakly agglutinated. The patient's RBCs were negative with the original anti-MAR but reacted as strongly as the positive control RBCs with the antibody made by the DCXe/DCXe person. CONCLUSION: This is the first example of a MAR-like antibody made by a DCWe/DCWe woman. The specificity cannot be called anti-MAR, because some MAR-negative samples react, albeit weakly. The original anti-MAR, made by a DCWe/DCXe woman, did not react with DCWe/DCWe, DCWe/DCXe, or DCXe/DCXe RBCs. It is apparent that the specificity of "anti-MAR" differs slightly, depending on the CW/CX status of the antibody maker.
Antibody Specificity↗
The low-incidence MNS antigens M(v), s(D), and Mit arise from single amino acid substitutions on GPB.
BACKGROUND: GPB carries 'N' at its N:-terminus and S and s, determined by a polymorphism at amino acid position 29 (Met29Thr). The low-incidence antigens M(v), s(D), and Mit are associated with weakened expression of S and/or s, and the purpose of this study was to define their molecular bases. METHODS: The GPB gene (GYPB) was sequenced after RT-PCR of RNA from four samples: two M(v)+, one s(D)+, and one Mit+. The point mutations observed were confirmed by sequencing of genomic DNA from these and other examples of s(D)+ and Mit+ samples. RESULTS: A point mutation of 65C>G observed in the M(v)+ samples predicted a change of Thr3Ser. A mutation of C>G at nucleotide 173 of the GYPB coding sequence, observed in two s(D)+ samples, predicted a change of Pro39Arg. Three Mit+ samples showed a nucleotide substitution of 161G>A, which predicted a change of Arg35His. Altered expression of S or s was confirmed by serologic tests. CONCLUSION: These results confirm that Arg35 is important for full expression of S. Pro39 and, surprisingly, Thr3 are also important for full expression of s. Furthermore, Thr3 must be essential for expression of 'N,' as M(v)+ RBCs lack 'N.'
Amino Acid Substitution↗
The first example of a paraben-dependent antibody to an Rh protein.
BACKGROUND: Parabens are added to a commercial LISS (C-LISS) to retard microbial growth. Paraben-dependent anti-Jk(a) has been detected by the use of C-LISS. CASE REPORT: Serum from a D+ woman reacted in antiglobulin tests with RBCs stored (2-4 hours, 22-25 degrees C) in C-LISS (Löw and Messeter formulation, Immucor). Freshly prepared C-LISS-suspended RBCs did not react; nor did RBCs stored in LISS-additive reagents, PEG, saline, or homemade LISS. RESULTS: Studies using C-LISS-stored RBCs revealed an antibody that reacted with D+ and rrV+ RBCs, but not with r'r, r"r, or rrV-VS- RBCs. All partial D RBC phenotypes tested reacted, as did D+LW-, rGr, r"Gr, r(y)r, r'(s)rV+VS+, and r'(s)rV-VS+ RBCs. The active ingredient in C-LISS was propylparaben. Other LISS ingredients were not required; saline solutions of propylparaben, ethylparaben, methyl salicylate, 2-phenoxyethanol, and butylparaben were active. Methylparaben and methyl-m-hydroxybenzoate were inactive. Reactivity to C-LISS-stored RBCs could not be inhibited by propylparaben. Reactivity with D+V- and D-V+VS+ RBCs was not separable by adsorption-elution. CONCLUSIONS: This antibody likely detects a neoantigen formed between active compounds and RBC membranes. Review of the structure of active compounds suggests that proximity between methyl and hydroxyl groups is important for binding with RBC membranes. The role of RhD is unclear; no single portion of RhD protein appears to be implicated.
Adult↗
DNA analysis for the Dombrock polymorphism.
BACKGROUND: RBC typing for Do(a) and Do(b) is notoriously difficult, and inaccurate typing can predispose patients to hemolytic transfusion reactions. The DO1/DO2 polymorphism is associated with three nucleotide changes: 378 C>T, 624 T>C and 793 A>G. While the 378 C>T- and 624 T>C-containing codons are silent mutations, the 793 A>G polymorphism in codon 265 encodes asparagine for Do(a) and aspartic acid for Do(b). STUDY DESIGN AND METHODS: Described here are two PCR-RFLP assays, one using the Mnl I site associated with 624C (DO2) and the other altering two nucleotides within the sense primer, which allows recognition of 793G by the Eam 1105 I. RESULTS: The assays have been performed on over 100 samples for which the RBC typing of one or both antigens was known. Eight samples had been historically mistyped by hemagglutination. CONCLUSION: This RFLP assay provides a practical method for typing donor blood for Dombrock alleles.
Base Sequence↗
Immunization of transgenic mice for production of MoAbs directed at polymorphic blood group antigens.
BACKGROUND: Antibodies of human origin for blood typing are increasingly difficult to obtain, and, despite aggressive efforts, MoAbs with specificities to several blood group polymorphisms have eluded production. As an approach for the generation of MoAbs with defined specificities, the feasibility of immunizing mice that are transgenic for the target polymorphism, Fy(a)/Fy(b) of the Duffy blood group system, was tested with a source of the antithetical antigen. STUDY DESIGN AND METHODS: Nontransgenic mice were immunized with recombinant Fy(b), and transgenic mice expressing human Fy(b) were immunized with recombinant Fy(a). RESULTS: Immunization of the nontransgenic mice resulted in the production of MoAbs to the Duffy protein, but not to the Fy(a)/Fy(b) blood group polymorphism. However, immunization of the transgenic mice resulted in production of the first example of murine Fy(a) MoAb (MIMA-19). This antibody is being used to screen for Fy(a-) blood donors and has been evaluated by many laboratories in an international workshop. CONCLUSION: This approach provides an effective method for producing MoAbs with specificities to polymorphic epitopes. These MoAbs are needed in transfusion medicine to identify antigen-negative donors and to alleviate the critical shortage of blood bank typing reagents, which currently are available only from human-derived sources.
Animals↗
Molecular basis of the Dombrock null phenotype.
BACKGROUND: The Dombrock blood group system consists of two antithetical antigens, Do(a) and Do(b), and three high-incidence antigens, Gregory (Gy(a)), Holley (Hy), and Joseph (Jo(a)). The null phenotype of the Dombrock blood group system (Do(null)) was identified when it was found that Gy(a-) RBCs also lack Do(a), Do(b), Hy, and Jo(a). STUDY DESIGN AND METHODS: DNA from three Gy(a-) persons was analyzed. PCR products for each of the three DO exons and their flanking intronic regions were sequenced in both directions. The cDNA from two of the people was subjected to PCR using primers in exon 1 and exon 3, and the products were sequenced. RESULTS: The Do(null) phenotype is associated with a single nucleotide mutation in the acceptor splice site of DO (IVS1-2a>g), which results in outsplicing of exon 2. CONCLUSION: Outsplicing of exon 2 is predicted to cause a -1 frameshift and a premature stop codon. Any product of such a transcript would lack the glycosyl-phosphatidylinositol-anchor motif, and RBCs would be devoid of the Do glycoprotein.
Amino Acid Sequence↗
Adenoma characteristics as risk factors for recurrence of advanced adenomas.
BACKGROUND AND AIMS: The link between adenoma characteristics at baseline colonoscopy and adenoma recurrence is poorly understood. We assessed whether the number, size, location, or histology of resected adenomas was related to the probability of recurrence of advanced lesions. METHODS: Analyses were based on 1287 men and women in the wheat bran fiber (WBF) study, a randomized, double-blind trial of WBF as a means of decreasing the probability of adenoma recurrence over a period of 3 years. Multiple logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Recurrence of advanced adenomas (>1 cm or tubulovillous/villous histology) was higher among individuals with adenomas >1 cm compared with those with adenomas <0.5 cm (OR, 2.69; 95% CI, 1.34-5.42) and among those with proximal than those with distal adenomas (OR, 1.65; 95% CI, 1.02-2.67). No association was observed for adenoma number or histology. A shift in location from the distal colon and rectum at baseline (54.6%) to more proximal recurrent adenomas (45.2%), including advanced lesions (42.8%), was observed. CONCLUSIONS: Large or proximally located adenomas are important indicators of recurrence of advanced lesions. Because most recurrences were detected in the proximal colon, careful surveillance of this area is warranted.
Adenoma↗