The Lutheran blood group glycoprotein, another member of the immunoglobulin superfamily, is widely expressed in human tissues and is developmentally regulated in human liver.

Glycoproteins expressing the Lutheran blood group antigens were isolated from human erythrocyte membranes and from human fetal liver. Amino acid sequence analyses allowed the design of redundant oligonucleotides that were used to generate a 459-bp, sequence-specific probe by PCR. A cDNA clone of 2400 bp was isolated from a human placental lambda gt 11 library and sequenced, and the deduced amino acid sequence was studied. The predicted mature protein is a type I membrane protein of 597 amino acids with five potential N-glycosylation sites. There are five disulfide-bonded, extracellular, immunoglobulin superfamily domains (two variable-region set and three constant-region set), a single hydrophobic, membrane-spanning domain, and a cytoplasmic domain of 59 residues. The overall structure is similar to that of the human tumor marker MUC 18 and the chicken neural adhesion molecule SC1. The extracellular domains and cytoplasmic domain contain consensus motifs for the binding of integrin and Src homology 3 domains, respectively, suggesting possible receptor and signal-transduction function. Immunostaining of human tissues demonstrated a wide distribution and provided evidence that the glycoprotein is under developmental control in liver and may also be regulated during differentiation in other tissues.

Blood group antigens & antibodies as applied to blood transfusion.

Includes bibliographical references.

Effect of immunizations on blood group antibody production; progress report,

Mode of access: Internet.

The blood-vascular system of the tile-fish, Lopholatilus chamaeleonticeps.

From Bulletin of the Bureau of Fisheries, vol. xxiv, 1904.

Association of ABO blood group and Plasmodium falciparum malaria among Children in the Federal Capital Territory, Nigeria

The ABO and Rhesus blood group systems are very important clinical tools that are commonly used in blood transfusion and their associations with various disease conditions have been widely reported. This study investigated the distribution of these blood group systems and assessed the association of malaria infection with the ABO blood groups among children in Federal Capital Territory, Abuja. Blood specimens from deep finger pricks of 730 children aged between 0-2 years were examined for malaria parasites using Field stains method. ABO and Rhesus blood group antigens tests were also performed using standard tile protocols. Of all the children admitted into the study, 445 were sick while 285 were apparently healthy. The prevalence of malaria parasites was significantly higher (P = 0.00047) among the sick children (69.8%) than the apparently healthy children (30.2%). The most prevalent blood group was O (55.7%) and the Rhesus D antigen was positive for 98.4% of all the children. The prevalence of blood group B among the sick children was significantly lower (P = 0.00373) than the other blood group types. There is no association between malaria infection and ABO blood groups but the prevalence of higher malaria parasite density was significantly greater (P = 0.0404) in children with blood group A (7.7%). In conclusion, blood group O was the most prevalent blood group in the study and children with blood group A appeared to be more susceptible to higher level of malaria parasitemia.

Linearity analysis and comparison study on the epoc® point-of-care blood analysis system in cardiopulmonary bypass patients

The epoc® blood analysis system (Epocal Inc., Ottawa, Ontario, Canada) is a newly developed in vitro diagnostic hand-held analyzer for testing whole blood samples at point-of-care, which provides blood gas, electrolytes, ionized calcium, glucose, lactate, and hematocrit/calculated hemoglobin rapidly. The analytical performance of the epoc® system was evaluated in a tertiary hospital, see related research article “Analytical evaluation of the epoc® point-of-care blood analysis system in cardiopulmonary bypass patients” [1]. Data presented are the linearity analysis for 9 parameters and the comparison study in 40 cardiopulmonary bypass patients on 3 epoc® meters, Instrumentation Laboratory GEM4000, Abbott iSTAT, Nova CCX, and Roche Accu-Chek Inform II and Performa glucose meters.

Heterogeneity evidence and linkage studies on Charcot-Marie-Tooth disease

Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an autosomal dominant disorder originally localized to chromosome 1 by linkage to the Duffy blood group. Studies have since shown that the disorder may be heterogeneous, as not all families show this linkage. We tested genetic heterogeneity by the HOMOG computer program in 15 CMT1 pedigrees informative for Duffy. We detected no evidence for heterogeneity in this sample, but when we combined results with previously published lod scores, heterogeneity was statistically significant. Twelve of the 15 families studied did not show linkage to Duffy. We found six of these families to be informative for a chromosome 19 marker, apolipoprotein CII(ApoC2). Despite a previous report showing probable linkage of a non-Duffy-linked CMT1 pedigree to two chromosome 19 markers, we did not detect significant linkage of ApoC2 to CMT1 in these families.

Sequence, evolution and ligand binding properties of mammalian Duffy antigen/receptor for chemokines

The Duffy antigen/receptor for chemokine, DARC, acts as a widely expressed promiscuous chemokine receptor and as the erythrocyte receptor for Plasmodium vivax. To gain insight into the evolution and structure/function relations of DARC, we analyzed the binding of anti-human Fy monoclonal antibodies (mAbs) and human chemokines to red blood cells (RBCs) from 11 nonhuman primates and two nonprimate mammals, and we elucidated the structures of the DARC genes from gorilla, gibbon, baboon, marmoset, tamarin, night monkey and cattle. CXCL-8 and CCL-5 chemokine binding analysis indicated that the promiscuous binding profile characteristic of DARC is conserved across species. Among three mAbs that detected the Fy6 epitope by flow cytometric analysis of human and chimpanzee RBCs, only one reacted with night monkey and squirrel monkey. Only chimpanzee RBCs bound a significant amount of the anti-Fy3 mAb. Fy3 was also poorly detected on RBCs from gorilla, baboon and rhesus monkey, but not from new world monkeys. Alignment of DARC homologous sequences allowed us to construct a phylogenetic tree in which all branchings were in accordance with current knowledge of primate phylogeny. Although DARC was expected to be under strong internal and external selection pressure, in order to maintain chemokine binding and avoid Plasmodium vivax binding, respectively, our present study did not provide arguments in favor of a selection pressure on the extracellular domains involved in ligand specificity. The amino acid variability of DARC-like polypeptides was found to be well correlated with the hydrophylicity indexes, with the highest divergence on the amino-terminal extracellular domain. Analysis of the deduced amino acid sequences highlighted the conservation of some amino acid residues, which should prove to be critical for the structural and functional properties of DARC.

ABO, Lewis, secretor and non-secretor phenotypes in patients infected or uninfected by the Helicobacter pylori bacillus

CONTEXT: Epidemiological studies have demonstrated higher frequencies of the O blood group and the non-secretor phenotype of ABH antigens among patients suffering from peptic ulcers. Since Helicobacter pylori has been established as the main etiological factor in this disease, controversies about the associations of the ABO and Lewis blood group phenotypes and secretor and non-secretor phenotypes in relation to susceptibility towards infection by this bacillus have been presented. OBJECTIVE: To verify the frequencies of ABO, Lewis blood group phenotypes, secretor and non-secretor phenotypes in patients infected or uninfected by H. pylori. DESIGN: Cross-sectional study. SETTING: Outpatient clinic. PARTICIPANTS: One hundred and twenty patients with dyspeptic symptoms who underwent endoscopy. MAIN MEASUREMENTS: ABO and Lewis blood group phenotypes were determined by a standard hemagglutination test and the secretor and non-secretor phenotypes were evaluated by saliva samples using the inhibitor hemagglutination test. RESULTS: The diagnosis of infection, made via breath and urea tests and confirmed using polymerase chain reaction (PCR) in gastric biopsy fragments, showed the presence of H. pylori in 61.7% of the patients and absence in 38.3%. The differences between the frequencies of the ABO blood group phenotypes among infected (A 27.0%; B 12.2%; AB 4.0% and O 56.8%) and uninfected patients (A 58.7%; B 13.0%; AB 4.3% and O 24.0%) were significant. The Lewis blood type, secretor and non-secretor phenotypes showed homogeneous distribution between the groups of patients analyzed. CONCLUSIONS: Our results suggest that the infection of H. pylori can be related to ABO blood groups but not to the Lewis blood group nor to secretor and non-secretor phenotypes. Copyright©2002, Associação Paulista de Medicina.

Estudo da associação entre o sistema histo-sangüíneo ABO e a malária por Plasmodium falciparum na Amazônia brasileira

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Molecular analysis of three FUT3 gene single nucleotide polymorphisms and their relationship with the lewis erythrocytary phenotype in a human population of japanese-ancestry living in Tomé Açu, a town in the Brazilian Amazon

The Lewis blood group system involves two major antigens, Le^ª and Le^b. Their antigenic determinants are not primary gene products but are synthesized by the transfer of sugar subunits to a precursory chain by a specific enzyme which is the product of the FUT3 gene (Lewis gene). The presence of three FUT3 gene single nucleotide polymorphisms (SNPs) (59T > G; 508G > A and 1067T > A) was related to the Lewis phenotype of erythrocytes from 185 individuals of Japanese ancestry living in the town of Tomé-Açu in the Brazilian Amazon region. This relationship was detected using a serological hemagglutination test and the Dot-ELISA assay along with the molecular technique PCR-RFLP. We found that the three SNPs investigated in this study only accounted for a proportion of the Lewis-negative phenotype of the erythrocytes.

Molecular analysis of three FUT3 gene single nucleotide polymorphisms and their relationship with the lewis erythrocytary phenotype in a human population of japanese-ancestry living in Tomé Açu, a town in the Brazilian Amazon

The Lewis blood group system involves two major antigens, Le^a and Le^b. Their antigenic determinants are not primary gene products but are synthesized by the transfer of sugar subunits to a precursory chain by a specific enzyme which is the product of the FUT3 gene (Lewis gene). The presence of three FUT3 gene single nucleotide polymorphisms (SNPs) (59T > G; 508G > A and 1067T > A) was related to the Lewis phenotype of erythrocytes from 185 individuals of Japanese ancestry living in the town of Tomé-Açu in the Brazilian Amazon region. This relationship was detected using a serological hemagglutination test and the Dot-ELISA assay along with the molecular technique PCR-RFLP. We found that the three SNPs investigated in this study only accounted for a proportion of the Lewis-negative phenotype of the erythrocytes.

Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene.

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P = 3.8 x 10(-5)), establishing a novel phenotype for this genetic variant.

Development of a Blood Antigen Molecular Profiling Panel using Genotyping Technologies for Patients Requiring Frequent Transfusions

Contexte. Les phénotypes ABO et Rh(D) des donneurs de sang ainsi que des patients transfusés sont analysés de façon routinière pour assurer une complète compatibilité. Ces analyses sont accomplies par agglutination suite à une réaction anticorps-antigènes. Cependant, pour des questions de coûts et de temps d’analyses faramineux, les dons de sang ne sont pas testés sur une base routinière pour les antigènes mineurs du sang. Cette lacune peut résulter à une allo-immunisation des patients receveurs contre un ou plusieurs antigènes mineurs et ainsi amener des sévères complications pour de futures transfusions. Plan d’étude et Méthodes. Pour ainsi aborder le problème, nous avons produit un panel génétique basé sur la technologie « GenomeLab _SNPstream» de Beckman Coulter, dans l’optique d’analyser simultanément 22 antigènes mineurs du sang. La source d’ADN provient des globules blancs des patients préalablement isolés sur papiers FTA. Résultats. Les résultats démontrent que le taux de discordance des génotypes, mesuré par la corrélation des résultats de génotypage venant des deux directions de l’ADN, ainsi que le taux d’échec de génotypage sont très bas (0,1%). Également, la corrélation entre les résultats de phénotypes prédit par génotypage et les phénotypes réels obtenus par sérologie des globules rouges et plaquettes sanguines, varient entre 97% et 100%. Les erreurs expérimentales ou encore de traitement des bases de données ainsi que de rares polymorphismes influençant la conformation des antigènes, pourraient expliquer les différences de résultats. Cependant, compte tenu du fait que les résultats de phénotypages obtenus par génotypes seront toujours co-vérifiés avant toute transfusion sanguine par les technologies standards approuvés par les instances gouvernementales, les taux de corrélation obtenus sont de loin supérieurs aux critères de succès attendus pour le projet. Conclusion. Le profilage génétique des antigènes mineurs du sang permettra de créer une banque informatique centralisée des phénotypes des donneurs, permettant ainsi aux banques de sang de rapidement retrouver les profiles compatibles entre les donneurs et les receveurs.