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Concept: Human blood group systems


BACKGROUND: Diets that are based on the ABO blood group system have been promoted over the past decade and claim to improve health and decrease risk of disease. To our knowledge, the evidence to support the effectiveness of blood type diets has not previously been assessed in the scientific literature. OBJECTIVE: In this current systematic review, published studies that presented data related to blood type diets were identified and critically appraised by using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. DESIGN: A systematic search was performed to answer the following question: In humans grouped according to blood type, does adherence to a specific diet improve health and/or decrease risk of disease compared with nonadherence to the diet? The Cochrane Library, MEDLINE, and Embase were systematically searched by using sensitive search strategies. RESULTS: Sixteen articles were identified from a total of 1415 screened references, with only one article that was considered eligible according to the selection criteria. The identified article studied the variation between LDL-cholesterol responses of different MNS blood types to a low-fat diet. However, the study did not directly answer the current question. No studies that showed the health effects of ABO blood type diets were identified. CONCLUSIONS: No evidence currently exists to validate the purported health benefits of blood type diets. To validate these claims, studies are required that compare the health outcomes between participants adhering to a particular blood type diet (experimental group) and participants continuing a standard diet (control group) within a particular blood type population.

Concepts: Blood, Red blood cell, Blood type, Cochrane Library, ABO blood group system, Blood types in Japanese culture, Human blood group systems, Blood type diet


Associations between blood type and disease have been studied since the early 1900s when researchers determined that antibodies and antigens are inherited. In the 1950s, the chemical identification of the carbohydrate structure of surface antigens led to the understanding of biosynthetic pathways. The blood type is defined by oligosaccharide structures, which are specific to the antigens, thus, blood group antigens are secondary gene products, while the primary gene products are various glycosyltransferase enzymes that attach the sugar molecules to the oligosaccharide chain. Blood group antigens are found on red blood cells, platelets, leukocytes, plasma proteins, certain tissues, and various cell surface enzymes, and also exist in soluble form in body secretions such as breast milk, seminal fluid, saliva, sweat, gastric secretions, urine, and amniotic fluid. Recent advances in technology, biochemistry, and genetics have clarified the functional classifications of human blood group antigens, the structure of the A, B, H, and Lewis determinants and the enzymes that produce them, and the association of blood group antigens with disease risks. Further research to identify differences in the biochemical composition of blood group antigens, and the relationship to risks for disease, can be important for the identification of targets for the development of nutritional intervention strategies, or the identification of druggable targets. For further resources related to this article, please visit the WIREs website.

Concepts: Immune system, Protein, Blood, Red blood cell, Blood type, Hematology, ABO blood group system, Human blood group systems


Blood group antigens represent polymorphic traits inherited among individuals and populations. At present, there are 34 recognized human blood groups and hundreds of individual blood group antigens and alleles. Differences in blood group antigen expression can increase or decrease host susceptibility to many infections. Blood groups can play a direct role in infection by serving as receptors and/or coreceptors for microorganisms, parasites, and viruses. In addition, many blood group antigens facilitate intracellular uptake, signal transduction, or adhesion through the organization of membrane microdomains. Several blood groups can modify the innate immune response to infection. Several distinct phenotypes associated with increased host resistance to malaria are overrepresented in populations living in areas where malaria is endemic, as a result of evolutionary pressures. Microorganisms can also stimulate antibodies against blood group antigens, including ABO, T, and Kell. Finally, there is a symbiotic relationship between blood group expression and maturation of the gastrointestinal microbiome.

Concepts: Immune system, Gene, Bacteria, Evolution, Blood, Blood type, ABO blood group system, Human blood group systems


Human blood group A and B glycosyltransferases (GTA, GTB) are highly homologous glycosyltransferases. A number of high-resolution crystal structures is available showing that these enzymes convert from an open conformation into a catalytically active closed conformation upon substrate binding. However, the mechanism of glycosyltransfer is still under debate, and the precise nature as well as the time scales of conformational transitions are unknown. NMR offers a variety of experiments to shine more light on these unresolved questions. Therefore, in a first step we have assigned all methyl resonance signals in MILVA labeled samples of GTA and GTB, still a challenging task for 70 kDa homodimeric proteins. Assignments were obtained from methyl-methyl NOESY experiments, and from measurements of lanthanide-induced pseudocontact shifts (PCS) using high resolution crystal structures as templates. PCSs and chemical shift perturbations, induced by substrate analogue binding, suggest that the fully closed state is not adopted in the presence of lanthanide ions.

Concepts: Protein, Blood, Blood type, Chemistry, Nuclear magnetic resonance, Hematology, ABO blood group system, Human blood group systems


Haemagglutination has been the gold standard for defining the blood group status. However, these tests depend upon the availability of specific and reliable antisera. Potent antisera for extended phenotyping are very costly, weakly reacting or available in limited stocks and unavailable for some blood group systems like Indian, Dombrock, Coltan, Diego etc. The Indian blood group system consists of two antithetical antigens, Ina and Inb. The Ina /Inb polymorphism arises from 252C > G missense mutation in the CD44 gene. This knowledge has allowed the development of molecular methods for genotyping IN alleles.

Concepts: Gene, Genetics, Allele, Evolution, Blood, Blood type, ABO blood group system, Human blood group systems


Crystallography has shown that human blood group A (GTA) and B (GTB) glycosyltransferases undergo transitions between “open”, “semi-closed”, and “closed” conformations upon substrate binding. However, the time scales of corresponding conformational reorientations are unknown. Crystal structures show that Trp and Met residues are located at “conformational hot spots” of the enzymes. Therefore, we have utilized 15N-side chain labeling of Trp residues, and 13C-methyl labeling of Met residues to study substrate induced conformational transitions of GTB. Chemical shift perturbations (CSPs) of Met and Trp residues in direct contact with substrate ligands reflect binding kinetics, whereas CSPs of Met and Trp residues at remote sites reflect conformational changes of the enzyme upon substrate binding. Acceptor binding is fast on the chemical shift time scale with rather small CSPs in the range of less than ca. 20 Hz. Donor binding matches the intermediate exchange regime yielding an estimate for exchange rate constants around 200 - 300 Hz. Donor or acceptor binding to GTB saturated with acceptor or donor substrate, respectively, is slow (<10 Hz) as are coupled protein motions, reflecting mutual allosteric control of donor and acceptor binding. Remote CSPs suggest that substrate binding drives the enzyme into the closed state required for catalysis. These findings should contribute to a better understanding of the mechanism of glycosyltransfer of GTA and GTB.

Concepts: Enzyme kinetics, Protein, Enzyme, Blood, Blood type, Hematology, ABO blood group system, Human blood group systems


Antibody-mediated rejection is a barrier to the clinical application of xenotransplantation, and xenoantigens play an important role in this process. Early research suggested that N-acetyl-D-galactosamine (GalNAc) could serve as a potential xenoantigen. GalNAc is the immunodominant glycan of the Sda antigen. Recently, knockout of β1,4-N-acetylgalactosaminyltransferase 2 (β1,4GalNAcT-II) from the pig results in a decrease in binding of human serum antibodies to pig cells. It is believed that this is the result of the elimination of the GalNAc on the Sda antigen, which is catalyzed by the enzyme, β1,4GalNAcT-II. However, research into human blood group antigens suggests that only a small percentage (1%-2%) of people express anti-Sda antibodies directed to Sda antigen, and yet a majority appear to have antibodies directed to the products of pig B4GALNT2. Questions can therefore be asked as to (i) whether the comprehensive structure of the Sda antigen in humans, that is, the underlying sugar structure, is identical to the Sda antigen in pigs, (ii) whether the human anti-Sda antibody binds ubiquitously to pig cells, but not to human cells, and (iii) what role the Sda++ (also called Cad) antigen is playing in this discrepancy. We review what is known about these antigens and discuss the discrepancies that have been noted above.

Concepts: Immune system, Antibody, Protein, Bacteria, Blood, Blood type, ABO blood group system, Human blood group systems


The ABO and rhesus (Rh) blood group antigens are the most frequently studied genetic markers in a large group of people. Blood type frequencies vary in different racial/ethnic groups. Our objective was to investigate the distribution of the ABO and rhesus (Rh) blood groups by molecular typing method in a population of Saudi stem cell donors. Our data indicate that the most common blood group in our population is group O followed by group A then group B, and finally, the least common is group AB.

Concepts: DNA, Gene, Genetics, Blood, Red blood cell, Blood type, ABO blood group system, Human blood group systems


Pain perception is associated with different phenotypic characteristics such as sex, eye, and hair color. Hence, it is assumed that ABO blood type can also affect pain perception.

Concepts: Gene, Blood, Red blood cell, Blood type, Blood bank, ABO blood group system, Blood types in Japanese culture, Human blood group systems


The DEL blood type, a very weak D variant, is a major concern in the field of transfusion medicine because of its potential to cause anti-D alloimmunization. We investigated the molecular basis of serologically D-negative phenotypes, including the DEL type, and the distribution of other blood group systems in the Korean population using the recently developed multiplex ligation-dependent probe amplification (MLPA) assay.

Concepts: Gene, Blood, Blood type, Hematology, Blood transfusion, Transfusion medicine, ABO blood group system, Human blood group systems