Red blood cell tension protects against severe malaria in the Dantu blood group.

Malaria has had a major effect on the human genome, with many protective polymorphisms-such as the sickle-cell trait-having been selected to high frequencies in malaria-endemic regions1,2. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals3-5, a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine. Until now, however, the protective mechanism has been unknown. Here we demonstrate the effect of Dantu on the ability of the merozoite form of the malaria parasite Plasmodium falciparum to invade red blood cells (RBCs). We find that Dantu is associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC-parasite receptor-ligand interactions. By following invasion using video microscopy, we find a strong link between RBC tension and merozoite invasion, and identify a tension threshold above which invasion rarely occurs, even in non-Dantu RBCs. Dantu RBCs have higher average tension than non-Dantu RBCs, meaning that a greater proportion resist invasion. These findings provide both an explanation for the protective effect of Dantu, and fresh insight into why the efficiency of P. falciparum invasion might vary across the heterogenous populations of RBCs found both within and between individuals.

Comparative analysis of asexual and sexual stage Plasmodium falciparum development in different red blood cell types.

BACKGROUND: Red blood cell (RBC) polymorphisms are suggested to influence the course of Plasmodium falciparum malaria. Whereas some variants have been found to be protective, others have been found to enhance parasite development. This study evaluated the effect of variant haemoglobin (Hb) and ABO blood groups on P. falciparum merozoite invasion, multiplication rates as well as gametocyte development. METHODS: Approximately 2.5 mL of venous blood was collected from each participant. Flow cytometry was used to determine the in vitro merozoite invasion rates of NF54 parasites into the blood of 66 non-parasitaemic individuals with variant Hb genotypes (HbSS, HbSC) and blood groups (A, B, O), which were then compared with invasion into HbAA blood. The ex vivo asexual parasite multiplication and gametocyte production rates of parasites from 79 uncomplicated malaria patients with varying Hb genotypes (HbAS, HbAC and HbAA) were also estimated using microscopy. RESULTS: Merozoite invasion rates were significantly reduced by about 50% in RBCs containing HbSS and HbSC relative to HbAA cells. The presence of blood group O and B reduced the invasion rates of HbSS by about 50% and 60%, respectively, relative to HbSC but the presence of blood group A removed the inhibitory effect of HbSS. The initial parasite densities in uncomplicated malaria patients with Hb genotypes HbAS and HbAC cells were similar but significantly lower than those with genotype HbAA. The ex vivo parasite multiplication rate, gametocytaemia and gametocyte conversion rates followed a similar trend but did not reach statistical significance (p > 0.05). CONCLUSIONS: Parasite invasion rate into erythrocytes is dependent on both erythrocyte blood group antigen and haemoglobin genotype as blood group O and B provided protection via reduced merozoite invasion in RBCs containing HbSS relative to HbSC. Regardless of haemoglobin type, greater than 70% malaria patients had circulating ring stage parasites that differentiated into stage II gametocytes in 4 days.

Does proliferation capacity of lymphocytes depend on human blood types?

In vitro human lymphocyte culture methodology is well established yet certain confounding factors such as age, medical history as well as individual's blood type may potentially modulate in vitro proliferation response. These factors have to be carefully evaluated to release reliable test report in routine cytogenetic evaluation for various genetic conditions, radiation biodosimetry, etc. With this objective, the current study was focused on analyzing the proliferation response of lymphocytes drawn from 90 individuals (21-29 years) with different blood types. The proliferation response was assessed in the cultured lymphocytes by cell cycle, mitotic index (MI), and nuclear division index (NDI) after stimulation with phytohaemagglutinin (PHA). To investigate the toxic effect on proliferation, MI was calculated in representative samples of each blood type were X-irradiated. The results showed that there was no significant difference among the cell cycle phases of lymphocytes in different blood types (P > 0.05). Similarly, both MI and NDI of lymphocytes derived from different blood types also did not show significant difference ( P > 0.05). The extensive interindividual variation within and among the blood types is likely responsible for the lack of significant difference in lymphocyte proliferation. Although spontaneous proliferation efficiency of lymphocytes of different blood types after PHA stimulation was grossly similar, the MI observed after radiation exposure showed a significant difference ( P < 0.05) indicating a differential proliferation response among the blood types. Our results suggest that the blood types did not have any impact on PHA-induced proliferation; however, a specific differential lymphocyte proliferation observed after radiation exposure needs to be considered.

Binding of rabbit hemorrhagic disease virus-like particles to host histo-blood group antigens is blocked by antisera from experimentally vaccinated rabbits.

During infection host histo-blood group antigens (HBGAs) act as attachment factors that interact with rabbit hemorrhagic disease virus (RHDV) and participate in the infectious process. In the present study, baculovirus expressing recombinant RHDV capsid protein (VP60r) as a vaccine immunogen was used to test its antigenicity and immunogenicity via immunization experiments. Each group of rabbits immunized with VP60r was found to be fully protected against RHDV challenge. The duration of immunity of the vaccine following the inoculation of a single dose was determined to be at least 240 days. RHDV-specific humoral responses in antisera from inoculated rabbits were analyzed using VP60r virus-like particle (VLP)-based ELISA. Anti-VP60-specific antibody was produced by 7 days post-primary immunization. Following this stage, the levels of this antibody increased steadily, peaking at 90 days and maintaining a high level until 240 days. We developed a synthetic carbohydrate assay to detect blockage in attachment of RHDV VLPs to HBGAs by the rabbit antisera. On day 7 post-immunization, serum samples were demonstrated to block the binding of H type 2 to RHDV VLPs, with a blocking rate of almost 60%, a value that then increased steadily over time. From day 60 to day 240 post-immunization, serum samples completely blocked the binding of H type 2 to RHDV VLPs, with a blocking rate of almost 100%. This indicated that VP60-induced antibodies neutralize the interaction of RHDV with HBGAs.

Frequency of DEA 1 antigen in 1037 mongrel and PUREBREED dogs in ITALY.

BACKGROUND: The prevalence of dog erythrocyte antigen (DEA 1) in canine population is approximately 40-60%. Often data are limited to a small number of breeds and/or dogs. The aims of this study were to evaluate frequency of DEA 1 in a large population of purebred and mongrel dogs including Italian native breeds and to recognize a possible association between DEA 1 and breed, sex, and genetic and phenotypical/functional classifications of breeds. Frequencies of DEA 1 blood group collected from screened/enrolled blood donors and from healthy and sick dogs were retrospectively evaluated. The breed and the sex were recorded when available. DEA 1 blood typing was assessed by immunocromatographic test on K3EDTA blood samples. The prevalence of DEA 1 antigen was statistically related to breed, gender, Fédération Cynologique Internationale (FCI) and genotypic grouping. RESULTS: Sixty-two per cent dogs resulted DEA 1+ and 38% DEA 1-. DEA 1- was statistically associated with Dogo Argentino, Dobermann, German Shepherd, Boxer, Corso dogs, the molossian dogs, the FCI group 1, 2 and 3 and the genetic groups "working dogs" and "mastiff". DEA 1+ was statistically associated with Rottweiler, Briquet Griffon Vendéen, Bernese mountain dog, Golden Retriever, the hunting breeds, the FCI group 4, 6, 7 and 8 and the genetic groups "scent hounds" and "retrievers". No gender association was observed. CONCLUSIONS: Data obtained by this work may be clinically useful to drive blood donor enrollment and selection among different breeds.

Frequencies of red blood cell major blood group antigens and phenotypes in the Chinese Han population from Mainland China.

Alloantibodies directed to red blood cell (RBC) antigens play an important role in alloimmune-mediated haemolytic transfusion reactions and haemolytic disease of the foetus and newborn. The frequencies and phenotypes of RBC antigens are different in populations from different geographic areas and races. However, the data on major blood group antigens in the Chinese Han population from Mainland China are still very limited; thus, we aimed to investigate them in this study. A total of 1412 unrelated voluntary Chinese Han blood donors were randomly recruited. All donors were typed for blood group antigens: D, C, c, E, e, C(w) , Jk(a) , Jk(b) ,M, N, S, s, Le(a) , Le(b) , K, k. Kp(a) , Kp(b) , Fy(a) , Fy(b) , Lu(a) , Lu(b) , P1 and Di(a) using serological technology. Calculations of antigen and phenotype frequencies were expressed as percentages and for allele frequencies under the standard assumption of Hardy-Weinberg equilibrium. Amongst the Rh antigens, D was the most common (98.94%) followed by e (92.28%), C (88.81%), c (58.43%), E (50.78%) and C(w) (0.07%) with DCe/DCe (R1 R1 , 40.72%) being the most common phenotype. In the Kell blood group system, k was present in 100% of the donors and a rare phenotype, Kp (a+b+), was found in 0.28% of the donors. For the Kidd and Duffy blood group systems, Jk (a+b+) and Fy (a+b-) were the most common phenotypes (44.05% and 84.35%, respectively). In the MNS blood group system, M+N+S-s+ (45.54%) was the most common, whereas M+N-S-s- and M-N+S-s- were not found. The rare Lu (a-b-) and Lu (a+b+) phenotypes were identified in 0.43% and 1.13% of the donors, respectively. Le(a) and Le(b) were seen in 17.92% and 63.03% of donors, respectively. The frequency of Di(a) was 4.75%, which was higher than in the Chinese population in Taiwan region or the Caucasian and Black populations (P < 0.0001). This study systematically describes the frequencies of 24 blood group antigens in the Chinese Han population from Mainland China. The data can be helpful in creating a donor database for preparation of indigenous cell panels and providing antigen-negative blood to patients with multiple alloantibodies.

Red cell antigen prevalence predicted by molecular testing in ethnic groups of South Texas blood donors.

Alloimmunization to red blood cell antigens is seen in patients receiving chronic blood transfusion. Knowing the prevalence of blood group antigens of the different ethnicities of South Texas donors can provide better management of rare blood inventory for patients in this geographical area. A total of 4369 blood donors were tested and analyzed for various antigens in the following blood group systems: ABO, Rh, Kell, Duffy, Kidd, MNS, Lutheran, Dombrock, Landsteiner-Wiener, Diego, Colton, and Scianna. Donors tested to be group 0 or A were serologically tested for the Rh (C, E, c, e) antigens. Those that tested as presumably R1R1, R2R2, or Ror were then genotyped. Donors constituted three major ethnicities: black (18.3%), Hispanic (36.3%), and Caucasian (41.1%); ethnicities comprised of Asian, American Indian, multiracial, and other accounted for the remaining donors (4.3%). The most likely common Rh phenotype for each ethnicity is as follows: black -Ror (44.4%), Hispanic -R1R1 (59.0%), and Caucasian -R1R1 (38.9%). The prevalence of Kell, Duffy, and Kidd blood group system antigens in black and Caucasian donors is comparable with published reports for the entire U.S. The black South Texas donor population had an 8.8 percent increase in prevalence of the Fy(a+b-) phenotype as compared with these published reports; the Hispanic South Texas donor population had a prevalence of 36.1 percent of the Fy(a+b-) phenotype. Regarding the Diego blood group system, the Hispanic donor population in South Texas had a prevalence of 93.5 percent for the Di(a-b+) phenotype as compared with published reports for the entire U.S. (>99.9%). The Hispanic population had a prevalence of 7.9 percent of donors testing as M-N+S-s+ as compared with 20.2 percent and 15.6 percent for black and Caucasian donors, respectively. This study helped us determine the prevalence of each of the blood group antigens in the South Texas donor population to establish and maintain adequate rare inventory of each. Molecular red blood cell genotyping allows transfusion services to increase their availability of rare phenotypes for chronically transfused patients.

[Blood groups - minuses and pluses. Do the blood group antigens protect us from infectious diseases?]. / Grupy krwi-minusy i plusy. Czy antygeny grupowe krwi chronia nas przed chorobami zakaznymi?

Human blood can be divided into groups, which is a method of blood classification based on the presence or absence of inherited erythrocyte surface antigens that can elicit immune response. According to the International Society of Blood Transfusion, there are 341 blood group antigens collected in 35 blood group systems. These antigens can be proteins, glycoproteins or glycosphingolipids, and function as transmembrane transporters, ion channels, adhesion molecules or receptors for other proteins. The majority of blood group antigens is present also on another types of cells. Due to their localization on the surface of cells, blood group antigens can act as receptors for various pathogens or their toxins, such as protozoa (malaria parasites), bacteria (Helicobacter pylori, Vibrio cholerae and Shigella dysenteriae) and viruses (Noroviruses, Parvoviruses, HIV). If the presence of group antigen (or its variant which arised due to mutation) is beneficial for the host (e.g. because pathogens are not able to bind to the cells), the blood group may become a selection trait, leading to its dissemination in the population exposed to that pathogen. There are thirteen blood group systems that can be related to pathogen resistance, and it seems that the particular influence was elicit by malaria parasites. It is generally thought that the high incidence of blood groups such as O in the Amazon region, Fy(a-b-) in Africa and Ge(-) in Papua-New Guinea is the result of selective pressure from malaria parasite. This review summarizes the data about relationship between blood groups and resistance to pathogens.

International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology: Cancun report (2012).

The International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology convened during the International congress in Cancun, July 2012. This report details the newly identified antigens in existing blood group systems and presents three new blood group systems.

Molecular approaches to transfusion medicine in Polynesians and Maori in New Zealand.

In recent years, with the application of genotyping technology, there has been a substantial increase in the number of reported blood group alleles. This survey was designed to evaluate new molecular blood group genotyping methods and compile reference blood group data sets for Polynesian and Maori subjects. Subsequent analyses of these results were used to calculate probability of random match, to trace Polynesian ancestry and migration patterns and to reveal past and present episodes of genetic admixture. Genomic DNA samples from Maori and Polynesian subjects were drawn from the Victoria University of Wellington DNA Bank and genotyped using combination of commercial PCR-SSP kits, hybridization SNP assay services or sequence-based typing. This survey also involves compilation of serological ABO and Rhesus blood group data from RakaiPaaka Iwi tribal members for comparison with those generated during our molecular blood group study. We observed perfect consistency between results obtained from all molecular methods for blood group genotyping. The A, O, DCcEe, DCCee, MNs, K-k+, Jk(a+b-), Jk(a+b+), Fy(a+b-), Fy(a+b+), Di(a+b-), Co(a+b-) and Do(a-b+) were predominant blood group phenotypes in both Polynesians and Maori. Overall, our survey data show only small differences in distributions of blood group phenotypes between Polynesian and Maori groups and their subgroups. These differences might be associated with selection, population history and gene flow from Europeans. In each case, we estimate that patients with certain blood groups have a very low probability of an exact phenotypic match, even if the patients were randomly transfused with blood from donors of their own ethnicity. The best way to avoid haemolytic transfusion reaction in such cases is to perform a pretransfusion cross-match and recruit increased numbers of donors with rare phenotype profiles. The conclusion of this study is that application of molecular method covering as many known variants as possible may help to improve the accuracy blood group genotyping and potentially conserve the routine requirements of transfusion centres.

Prevalence of dog erythrocyte antigen 1.1 in dogs in Switzerland evaluated with the gel column technique.

Canine blood typing has become an established and essential laboratory test due to the rising demand for safe and efficient blood transfusions. The most immunogenic and clinically important blood type is DEA 1.1. Little is known about DEA 1.1 frequencies or special characteristics among different canine breeds. 304 dogs were tested for DEA 1.1. DEA 1.1-typing was performed using a commercial gel column technique (ID-Gel Test Canine DEA 1.1, DiaMed, Cressier, Switzerland). Fifty-three percent of all tested dogs reacted positive for DEA 1.1, whereas 49 % of the mixed breeds tested DEA 1.1-positive. All Bernese mountain dogs (n = 22) and Rottweilers (n = 9) tested positive for DEA 1.1, while all Boxers (n = 8), Flat-Coated Retrievers (n = 9), and Border Collies (6) tested negative for DEA 1.1. The prevalence of DEA 1.1 in dogs in Switzerland was found to be comparable to that reported from other countries. The tested breeds were found to differ considerably in the frequency of DEA 1.1. This knowledge is useful for selection of blood donors. However, DEA 1.1 blood typing of donor and recipient prior to transfusion and cross matching in sensitized dogs is unavoidable.

Secretors of HBGA and Susceptibility to Norovirus and Rotavirus Diarrhea.

Histo-blood group antigen contains oligosaccharides that serve as receptors for norovirus (NoV) and rotavirus (RV). The receptors are only present on the surface of intestinal mucosal epithelial cells of secretors; therefore, secretors are susceptible to NoV and RV diarrhea and nonsecretors are resistant. The prevalence of secretors in different countries varies between 50% and 90%. Secretor rates evolved in response to environmental pressures such as infectious diseases.

Blood groups: the past 50 years.

Since the first issue of TRANSFUSION in 1961, there has been a tremendous expansion in not only the number of blood group antigens identified but also in our knowledge of their biochemical basis, function, and more recently, associated DNA changes. As certain techniques became available, our ability to discover and elucidate blood group antigens and appreciate their contribution to biology became possible. In particular, Western blotting, monoclonal antibodies, cloning, and polymerase chain reaction-based assays have led to an explosion of our knowledge base. The study of blood groups has had a significant effect on human genetics where they serve as useful markers in genetic linkage analyses. Indeed blood groups have provided several "firsts" in certain aspects of genetics. Blood group-null phenotypes, as natural human knockouts, have provided valuable insights into the importance of red blood cell membrane components. This review summarizes key aspects of the discovery of blood groups; the inconsistent terminology that has arisen; and the contribution of blood groups to genetics, safe transfusion, transplantation, evolution, and biology.

Consortium for Blood Group Genes (CBGG): 2009 report.

Consortium for Blood Group Genes is a worldwide organization whose goal is to have a vehicle to interact, establish guidelines, operate a proficiency program, and provide education for laboratories involved in DNA and RNA testing for the prediction of blood group, platelet, and neutrophil antigens. Currently, the consortium operates with representatives from Brazil, Canada, and the United States. Membership is voluntary with the expectation that members actively contribute to discussions involving blood group genetics. This year witnessed a change in the standing committee membership and the institution of a representative for the human platelet antigens group. Looking forward, the consortium sees challenges for the nomenclature of blood group alleles and user-required specifications for laboratory information systems to store genotype information.

Understanding blood groups and transfusion in nursing practice.

A donation of whole blood can be processed into red cells, platelets, fresh frozen plasma and cryoprecipitate. This processing permits individual blood components to be given to several different patients and transfusion of appropriate blood components according to the specific needs of the individual. Although blood transfusion may be perceived as a common practice, it is not without risk and all staff should be aware of their roles and responsibilities within this process. To help reduce the risks associated with transfusion, staff must be aware of local policies and procedures, receive the relevant transfusion training, and be assessed as competent.

[The red blood cell antigen terminologies]. / Les nomenclatures de groupes sanguins érythrocytaires.

Since the discovery of blood groups in humans, several hundred new red blood cell antigens have been identified. Multiple terminology modes have been used to denote each new antigen identified, but without any consistent rules, nor international consensus. This was largely due to the many discoverers of these antigens, using either letters of the alphabet, numbers, part of the patient or donor's name, place of discovery or animal names. Besides, alternative terminologies for the Rh system were implemented in the middle of the twentieth century (Rosenfield, Fisher-Race, Wiener). The International Society of Blood Transfusion described for the first time in 1980 the advantages of an alphanumeric and homogeneous nomenclature, keeping with the genetic bases of blood groups, as well as a classification of all RBC antigens within several families. A variant of this new terminology, exclusively numerical, was simultaneously established, mainly designed for computer data exchange. Nearly 30 years later, 308 red blood cell antigens are described within 30 systems, 12 collections, one 700 series and one 901 series of blood groups. Any person involved in the field of immuno-haematology must master both the usual and international nomenclatures. The Wiener nomenclature used for Rh haplotypes, still largely used today, is also important to be known. The systematic use of the international nomenclature should be strongly encouraged, either in the labelling of blood products, clinical laboratory reports or blood type cards.

Integrating molecular technologies for red blood cell typing and compatibility testing into blood centers and transfusion services.

Nucleic acid-based technology is now at a point where the field of transfusion medicine is ready for its widespread application. In the donor center, genotyping of red blood cell (RBC) products provides phenotype-matched products for special patient populations or antigen-negative products for patients with alloantibodies. In the immunohematology reference laboratory, molecular technologies aid in discerning blood types in the situation of a typing discrepancy and improve pretransfusion RBC testing reagents. In the hospital transfusion service, genotyping patients aids in providing phenotype-matched RBC products. In prenatal testing, genotyping for RHD aids in the decision for Rh immune globulin prophylaxis and predicting risk of hemolytic disease of the fetus and newborn. Before genotyping is accepted as the universal standard for pretransfusion and donor testing, important limitations of this technology must be addressed, including the fact that the genotype does not always predict the phenotype and the need for creating the ideal high-throughput platform. Clinical trials are needed to answer important questions, and a donor and patient database is needed. A stepwise plan for progressive introduction into the donor centers and transfusion services must be established. In conclusion, the field of transfusion medicine is ready to expand the use of molecular diagnostics.

Rapid, single-subject genotyping to predict red blood cell antigen expression.

Genotyping is useful to predict the expression of those RBC antigens for which antisera are difficult to obtain and to determine the probable phenotype of highly transfused patients, and it can be used to test stored DNA when a blood sample is not available. This study assessed a sequence-specific primer (SSP)-based genotyping system for blood group alleles suitable for the rapid testing of a small number of samples and assessed the use of stored whole blood. Genomic DNA was isolated from fresh and 1- and 2-week-old stored blood from 20 donors with known ABO and Rh phenotypes and was used for ABO, RHD, and RHCE genotyping using SSPs. The amplicons were analyzed using gel electrophoresis and a novel microfluidic on-chip electrophoresis system. Analysis of DNA from fresh and 1- and 2-week-old blood by SSP and gel electrophoresis yielded the correct ABO, RHD, and RHCE type in all samples, but with DNA from 2-week-old stored blood the amplicons were more difficult to visualize. Analysis of the same samples with the SSP on-chip electrophoresis assay correctly typed all samples except for one RHCE typing discrepancy of a fresh sample and one RHCE typing discrepancy of a 2-week-old sample. Analysis of amplicons by on-chip electrophoresis required one tenth the DNA that gel electrophoresis did and could be completed within 30 minutes compared with 2 hours with gel electrophoresis. Amplicons were also more readily visualized with on-chip electrophoresis. Fresh and 1- and 2-week-old samples could be ABO and RH genotyped with SSP. Analysis using on-chip electrophoresis was easier and more rapid than that using gel electrophoresis, but test reliability was slightly more variable.

The potential of blood group genotyping for transfusion medicine practice.

Molecular diagnostics is the fastest growing area of clinical laboratory medicine. The ability to rapidly amplify genes of bacterial, viral, or human origin, and the development of DNA array platforms, are driving a technology revolution in the clinical laboratory. A DNA-based testing approach is particularly applicable to blood bank and transfusion medicine for rapid, cost-effective antigen typing. Experience with DNA-based methods during the past decade has shown that these assays are reproducible and highly correlated with the RBC phenotype. The recent availability of automated, high-throughput, DNA-array platforms now moves testing from the reference laboratory setting into hospital and donor testing centers. This approach has the potential to revolutionize the process of locating antigen-negative donor units by testing for all clinically significant blood group antigens in a single assay. When partnered with the same extended typing of the patient, electronic selection of units antigen-matched at multiple blood group loci is then possible. This paper discusses the potential of this approach to improve transfusion therapy by reducing or eliminating alloantibody production in specific patient populations. These include patients facing long-term transfusion therapy and at high risk for sensitization; patients with warm autoantibodies when compatibility cannot be demonstrated by standard methods; and women for whom the production of atypical antibodies carries a risk for hemolytic disease of the fetus and newborn, or at the very least, monitoring for an at-risk pregnancy.