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Frontiers in Cellular and Infection... 2021The glycosyltransferases encoded by genes from the human ABO, Lewis, and Secretor histo-blood group systems synthesize part of the carbohydrate antigens in hematopoietic...
The glycosyltransferases encoded by genes from the human ABO, Lewis, and Secretor histo-blood group systems synthesize part of the carbohydrate antigens in hematopoietic and non-hematopoietic tissues. The combined action of these glycosyltransferases strongly influences cell, tissue, mucosa, and exocrine secretion carbohydrate phenotypes, including those serving as habitat for mutualistic and pathogenic microorganisms. A set of reports investigated associations between infection and the ABO histo-blood group system, but the results are contradictory. As uses the gastrointestinal tract as a route for infection, and in this organ, the expression of ABO, Lewis, and Secretor histo-blood group carbohydrates occurs, it is reasonable to suppose some biological relationship between them. This text reviewed association studies published in recent decades focusing on the potential contribution of the ABO, Lewis, and Secretor histo-blood group carbohydrates and infection by .
Topics: ABO Blood-Group System; Carbohydrates; Humans; Lewis Blood Group Antigens; Phenotype; Toxoplasma; Toxoplasmosis
PubMed: 34222043
DOI: 10.3389/fcimb.2021.671958 -
The Indian Journal of Medical Research Sep 2017The molecular basis of the blood group antigens was identified first in the 1980s and 1990s. Since then the importance of molecular biology in transfusion medicine has... (Review)
Review
The molecular basis of the blood group antigens was identified first in the 1980s and 1990s. Since then the importance of molecular biology in transfusion medicine has been described extensively by several investigators. Molecular genotyping of blood group antigens is one of the important aspects and is successfully making its way into transfusion medicine. Low-, medium- and high-throughput techniques have been developed for this purpose. Depending on the requirement of the centre like screening for high- or low-prevalence antigens where antisera are not available, correct typing of multiple transfused patients, screening for antigen-negative donor units to reduce the rate of alloimmunization, etc. a suitable technique can be selected. The present review discusses the evolution of different techniques to detect molecular genotypes of blood group systems and how these approaches can be used in transfusion medicine where haemagglutination is of limited value. Currently, this technology is being used in only a few blood banks in India. Hence, there is a need for understanding this technology with all its variations.
Topics: Blood Group Antigens; Blood Grouping and Crossmatching; Humans; Molecular Biology; Polymorphism, Single Nucleotide
PubMed: 29355136
DOI: 10.4103/ijmr.IJMR_914_16 -
Cold Spring Harbor Perspectives in... Oct 2015Hemolytic disease of the fetus and newborn (HDFN) is a condition characterized by a decreased lifespan of fetal red blood cells caused by maternally produced... (Review)
Review
Hemolytic disease of the fetus and newborn (HDFN) is a condition characterized by a decreased lifespan of fetal red blood cells caused by maternally produced allospecific antibodies transferred to the fetus during pregnancy. The antibodies bind to the corresponding blood group antigens on fetal red blood cells and induce hemolysis. Cell-free DNA derived from the conceptus circulates in maternal blood. Using next-generation sequencing (NGS), it can be determined if this cell-free fetal DNA encodes the corresponding blood group antigen that is the target of the maternal allospecific antibodies. This determination carries no risk to the fetus. It is important to determine if the fetus is at risk of hemolysis to enable timely intervention. Many tests for blood groups are based solely on the presence or absence of a single nucleotide polymorphism (SNP). Antenatal determination of fetal blood group by NGS analysis holds advantages over polymerase chain reaction (PCR) determination based on allele specific amplification.
Topics: Blood Group Antigens; DNA; Female; Fetus; Genotype; High-Throughput Nucleotide Sequencing; Humans; Pregnancy; Prenatal Diagnosis; Sequence Analysis, DNA
PubMed: 26511760
DOI: 10.1101/cshperspect.a023093 -
Journal of Virology Apr 2023Noroviruses are the leading cause of outbreaks of acute gastroenteritis. These viruses usually interact with histo-blood group antigens (HBGAs), which are considered...
Noroviruses are the leading cause of outbreaks of acute gastroenteritis. These viruses usually interact with histo-blood group antigens (HBGAs), which are considered essential cofactors for norovirus infection. This study structurally characterizes nanobodies developed against the clinically important GII.4 and GII.17 noroviruses with a focus on the identification of novel nanobodies that efficiently block the HBGA binding site. Using X-ray crystallography, we have characterized nine different nanobodies that bound to the top, side, or bottom of the P domain. The eight nanobodies that bound to the top or side of the P domain were mainly genotype specific, while one nanobody that bound to the bottom cross-reacted against several genotypes and showed HBGA blocking potential. The four nanobodies that bound to the top of the P domain also inhibited HBGA binding, and structural analysis revealed that these nanobodies interacted with several GII.4 and GII.17 P domain residues that commonly engaged HBGAs. Moreover, these nanobody complementarity-determining regions (CDRs) extended completely into the cofactor pockets and would likely impede HBGA engagement. The atomic level information for these nanobodies and their corresponding binding sites provide a valuable template for the discovery of additional "designer" nanobodies. These next-generation nanobodies would be designed to target other important genotypes and variants, while maintaining cofactor interference. Finally, our results clearly demonstrate for the first time that nanobodies directly targeting the HBGA binding site can function as potent norovirus inhibitors. Human noroviruses are highly contagious and a major problem in closed institutions, such as schools, hospitals, and cruise ships. Reducing norovirus infections is challenging on multiple levels and includes the frequent emergence of antigenic variants, which complicates designing effective, broadly reactive capsid therapeutics. We successfully developed and characterized four norovirus nanobodies that bound at the HBGA pockets. Compared with previously developed norovirus nanobodies that inhibited HBGA through disrupted particle stability, these four novel nanobodies directly inhibited HBGA engagement and interacted with HBGA binding residues. Importantly, these new nanobodies specifically target two genotypes that have caused the majority of outbreaks worldwide and consequently would have an enormous benefit if they could be further developed as norovirus therapeutics. To date, we have structurally characterized 16 different GII nanobody complexes, a number of which block HBGA binding. These structural data could be used to design multivalent nanobody constructs with improved inhibition properties.
Topics: Blood Group Antigens; Norovirus; Single-Domain Antibodies; Binding Sites; Cross Reactions; Thermodynamics; Crystallography, X-Ray; Protein Domains; Protein Binding; Models, Molecular
PubMed: 36971561
DOI: 10.1128/jvi.01833-22 -
Immunohematology 2011The Scianna system was named in 1974 when it was appreciated that two antibodies described in 1962 in fact identified antithetical antigens. However, it was not until... (Review)
Review
The Scianna system was named in 1974 when it was appreciated that two antibodies described in 1962 in fact identified antithetical antigens. However, it was not until 2003 that the protein on which antigens of this system are found and the first molecular variants were described. Scianna was the last previously serologically defined, protein-based blood group system to be characterized at the molecular level, marking the end of an era in immunohematology. This story highlights the critical role that availability of laboratory reagents for serologic testing has played in the initial characterization of a blood group and sets the stage for the development of new reagents, such as recombinant proteins, to assist in this process. The central role that genetics has played, both by classical pedigree analysis and by molecular techniques, in the discovery and characterization of this blood group is reviewed.
Topics: Amino Acid Sequence; Base Sequence; Blood Group Antigens; Blood Grouping and Crossmatching; Blood Transfusion; Butyrophilins; Gene Frequency; Humans; Isoantibodies; Linkage Disequilibrium; Molecular Sequence Data; Nucleotide Mapping; Pedigree; Polymorphism, Genetic
PubMed: 22356519
DOI: No ID Found -
Postepy Higieny I Medycyny... Jun 2015Human 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... (Review)
Review
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.
Topics: Blood Group Antigens; Blood Proteins; Disease Resistance; Humans; Malaria
PubMed: 26206987
DOI: 10.5604/17322693.1158795 -
Journal of Virology Oct 2022Human norovirus (HuNoV) infection is associated with an active FUT2 gene, which characterizes the secretor phenotype. However, nonsecretor individuals are also affected...
Human norovirus (HuNoV) infection is associated with an active FUT2 gene, which characterizes the secretor phenotype. However, nonsecretor individuals are also affected by HuNoV infection although in a lesser proportion. Here, we studied GII.3, GII.4, and GII.17 HuNoV interactions in nonsecretor individuals using virus-like particles (VLPs). Only GII.4 HuNoV specifically interacted with nonsecretor saliva. Competition experiments using histo-blood group antigen (HBGA)-specific monoclonal antibodies (MAbs) demonstrate that GII.4 VLPs recognized the Lewis a (Le) antigen. We also analyzed HuNoV VLP interactions on duodenum tissue blocks from healthy nonsecretor individuals. VLP binding was observed for the three HuNoV genotypes in 10 of the 13 individuals, and competition experiments demonstrated that VLP recognition was driven by an interaction with the Le antigen. In 3 individuals, binding was restricted to either GII.4 alone or GII.3 and GII.17. Finally, we performed a VLP binding assay on proximal and distal colon tissue blocks from a nonsecretor patient with Crohn's disease. VLP binding to inflammatory tissues was genotype specific since GII.4 and GII.17 VLPs were able to interact with regenerative mucosa, whereas GII.3 VLP was not. The binding of GII.4 and GII.17 HuNoV VLPs was linked to Le in regenerative mucosae from the proximal and distal colon. Overall, our data clearly showed that Le has a pivotal role in the recognition of HuNoV in nonsecretors. We also showed that Le is expressed in inflammatory/regenerative tissues and interacts with HuNoV in a nonsecretor individual. The physiological and immunological consequences of such interactions in nonsecretors have yet to be elucidated. Human norovirus (HuNoV) is the main etiological agent of viral gastroenteritis in all age classes. HuNoV infection affects mainly secretor individuals where ABO(H) and Lewis histo-blood group antigens (HBGAs) are present in the small intestine. Nonsecretor individuals, who only express Lewis (Le) antigens, are less susceptible to HuNoV infection. Here, we studied the interaction of common HuNoV genotypes (GII.3, GII.4, and GII.17) in nonsecretor individuals using synthetic viral particles. Saliva binding assays showed that only GII.4 interacted with nonsecretor saliva via the Lewis a (Le) antigen Surprisingly, the three genotypes interacted with nonsecretor enterocytes via the Le antigen on duodenal tissue blocks, which were more relevant for HuNoV/HBGA studies. The Le antigen also played a pivotal role in the recognition of GII.4 and GII.17 particles by inflammatory colon tissue from a nonsecretor Crohn's disease patient. The implications of HuNoV binding in nonsecretors remain to be elucidated in physiological and pathological conditions encountered in other intestinal diseases.
Topics: Antibodies, Monoclonal; Blood Group Antigens; Caliciviridae Infections; Crohn Disease; Genotype; Humans; Lewis Blood Group Antigens; Norovirus
PubMed: 36121297
DOI: 10.1128/jvi.00865-22 -
Blood Transfusion = Trasfusione Del... May 2012The storage of blood induces the formation of erythrocytes-derived microparticles. Their pathogenic role in blood transfusion is not known so far, especially the risk to...
BACKGROUND
The storage of blood induces the formation of erythrocytes-derived microparticles. Their pathogenic role in blood transfusion is not known so far, especially the risk to trigger alloantibody production in the recipient. This work aims to study the expression of clinically significant blood group antigens on the surface of red blood cells microparticles.
MATERIAL AND METHODS
Red blood cells contained in erythrocyte concentrates were stained with specific antibodies directed against blood group antigens and routinely used in immunohematology practice. After inducing erythrocytes vesiculation with calcium ionophore, the presence of blood group antigens was analysed by flow cytometry.
RESULTS
The expression of several blood group antigens from the RH, KEL, JK, FY, MNS, LE and LU systems was detected on erythrocyte microparticles. The presence of M (MNS1), N (MNS2) and s (MNS4) antigens could not be demonstrated by flow cytometry, despite that glycophorin A and B were identified on microparticles using anti-CD235a and anti-MNS3.
DISCUSSION
We conclude that blood group antigens are localized on erythrocytes-derived microparticles and probably keep their immunogenicity because of their capacity to bind specific antibody. Selective segregation process during vesiculation or their ability to elicit an immune response in vivo has to be tested by further studies.
Topics: Blood Group Antigens; Cell-Derived Microparticles; Erythrocytes; Flow Cytometry; Humans; Ultrasonography
PubMed: 22890266
DOI: 10.2450/2012.007S -
Hematology. American Society of... 2009DNA-based tests are increasingly being used to predict a blood group phenotype to improve transfusion medicine. This is possible because genes encoding 29 of the 30... (Review)
Review
DNA-based tests are increasingly being used to predict a blood group phenotype to improve transfusion medicine. This is possible because genes encoding 29 of the 30 blood group systems have been cloned and sequenced, and the molecular bases associated with most antigens have been determined. RBCs carrying a particular antigen, if introduced into the circulation of an individual who lacks that antigen (through transfusion or pregnancy), can elicit an immune response. It is the antibody from such an immune response that causes problems in clinical practice and the reason why antigen-negative blood is required for safe transfusion. The classical method of testing for blood group antigens and antibodies is hemagglutination; however, it has certain limitations, some of which can be overcome by testing DNA. Such testing allows conservation of antibodies for confirmation by hemagglutination of predicted antigen-negativity. High-throughput platforms provide a means to test relatively large numbers of donors, thereby opening the door to change the way antigen-negative blood is provided to patients and to prevent immunization. This review summarizes how molecular approaches, in conjunction with conventional hemagglutination, can be applied in transfusion medicine.
Topics: Adult; Blood Donors; Blood Group Antigens; Blood Group Incompatibility; Blood Grouping and Crossmatching; Blood Transfusion; DNA; Erythroblastosis, Fetal; Female; Fetal Blood; Gene Frequency; Hemagglutination Tests; Humans; Infant, Newborn; Mass Screening; Molecular Diagnostic Techniques; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Pregnancy; Prenatal Diagnosis; Rh-Hr Blood-Group System; Risk
PubMed: 20008196
DOI: 10.1182/asheducation-2009.1.171 -
Journal of Veterinary Internal Medicine May 2017The Dal blood group system was identified a decade ago by the accidental sensitization of a Dal- Dalmatian with a Dal+ blood transfusion. Similar Dal-related blood...
BACKGROUND
The Dal blood group system was identified a decade ago by the accidental sensitization of a Dal- Dalmatian with a Dal+ blood transfusion. Similar Dal-related blood incompatibilities have been suspected in other Dalmatians, Doberman Pinschers, and other breeds.
OBJECTIVES
To determine the prevalence and mode of inheritance of the Dal antigen expression in dogs.
ANIMALS
A total of 1130 dogs including 128 Dalmatians, 432 Doberman Pinschers, 21 Shih Tzus, and 549 dogs of other breeds including 228 blood donors were recruited from North America between 2008 and 2015.
METHODS
Prospectively, dogs were blood typed for Dal applying a gel column technique using polyclonal canine anti-Dal sera. Pedigrees from 8 typed families were analyzed.
RESULTS
The prevalence of the Dal+ blood type varied between 85.6 and 100% in Dalmatians and 43.3-78.6% in Doberman Pinschers depending on geographical area. Dal- dogs were identified mostly in Dalmatians (15/128; 11.7%), Doberman Pinschers (183/432; 42.4%), and Shih Tzus (12/21; 57.1%), and sporadically in mixed-breed dogs (3/122; 2.5%), Lhasa Apsos (1/6) and Bichon Frises (1/3). Only 6/245 (2.4%) blood donors were found to be Dal-, including 5 Doberman Pinschers. The mode of inheritance of the Dal+ phenotype was determined to be autosomal dominant.
CONCLUSIONS AND CLINICAL IMPORTANCE
The high percentage of Dal- Doberman Pinchers, Dalmatians and Shih Tzus increases their risk of being sensitized by a blood transfusion from the common Dal+ donor. Extended Dal typing is recommended in those breeds and in dogs when blood incompatibility problems arise after initial transfusions.
Topics: Animals; Blood Group Antigens; Blood Grouping and Crossmatching; Dogs; Female; Genetic Predisposition to Disease; Male; Pedigree; Prevalence; United States
PubMed: 28391649
DOI: 10.1111/jvim.14693