Academic literature on the topic 'Lewis blood groups'

Abstract The relative contribution of founder effects and natural selection to the observed distribution of human blood groups has been debated since blood group frequencies were shown to differ between populations almost a century ago. Advances in our understanding of the migration patterns of early humans from Africa to populate the rest of the world obtained through the use of Y chromosome and mtDNA markers do much to inform this debate. There are clear examples of protection against infectious diseases from inheritance of polymorphisms in genes encoding and regulating the expression of ABH and Lewis antigens in bodily secretions particularly in respect of Helicobacter pylori, norovirus, and cholera infections. However, available evidence suggests surviving malaria is the most significant selective force affecting the expression of blood groups. Red cells lacking or having altered forms of blood group-active molecules are commonly found in regions of the world in which malaria is endemic, notably the Fy(a−b−) phenotype and the S-s− phenotype in Africa and the Ge− and SAO phenotypes in South East Asia. Founder effects provide a more convincing explanation for the distribution of the D− phenotype and the occurrence of hemolytic disease of the fetus and newborn in Europe and Central Asia.

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.

Rabbit antisera directed against human milk sialyloligosaccharides were used to detect specific monosialylgangliosides from the lipid fraction of human meconium. Gangliosides of this fraction were detected after thin layer chromatography by immuno-staining with specific anti-oligosaccharide sera. The monosialylganglioside fraction of human meconium was subjected to ozonolysis and alkali-fragmentation and the resulting ganglioside-derived oligosaccharides were reduced with NaB [³H]₄ and partially separated using paper chromatography. The [³H]-oligosaccharide alditols were assayed for binding to specific anti-oligosaccharide sera in a direct-binding radioimmunoassay using nitrocellulose filters to collect immune-complexes. Radiolabeled oligosaccharide alditols which were recognized by specific antisera were affinity purified by eluting nitrocelIulose filters containing antibody-oligosaccharide complexes or using columns of immobilized anti-oligosaccharide antibodies. Structural analyses of two sialyl[³H]tetrasaccharide alditols obtained in this way were carried out with sequential enzymatic degradation using specific exoglycosidases. The products of enzymatic digestions were identified by cochromatography in paper with known standards. Data obtained from these experiments are consistent with the presence of the following, previously unidentified gangliosides in human meconium: NeuAcα2-3Galβ1-3GlcNAcβ1-3Galβ1-4Glc-cer Galβ1-3[NeuAcα2-6]GlcNAcα1-3Galβ1-4Glc-cer
Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004.
Vita.
Includes bibliographical references.
Cell-surface carbohydrates are markers of specific cell types. These oligosaccharides are involved in recognition, adhesion, and signal transduction events. Advances in molecular glycobiology rely heavily on straightforward access to structurally defined oligosaccharides, but traditional syntheses of complex carbohydrates have been very laborious. Development of a novel linker and monitoring of each glycosylation reaction during automated solid-phase oligosaccharide synthesis allowed for the rapid synthesis of three Lewis-type cell surface oligosaccharides. The assembly of the nonasaccharide adenocarcinoma marker Le[superscript]y-Le[superscript]x monosaccharide building blocks was achieved in just 23 hours, while the syntheses of the tumor markers Lewis X, a pentasaccharide, and Lewis Y, a hexasaccharide, required only 12 and 14 hours respectively. The automation of carbohydrate synthesis greatly accelerates access to molecules for biological study and vaccine development.
by Kerry Routenberg Love.
Ph.D.

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Introduction. The spondyloarthritis encomprises a group of diseases strongly associated with HLA-B*27 gene. It has been proposed that genes not belonging to the major histocompatibility complex human influence the genesis of these diseases especially in patients HLA-B*27 negative. Objectives. The aim of this study was to test the hypothesis that the antigens of the ABO, Secretor and Lewis histo-blood systems are associated with spondyloarthritis, especially ankylosing spondylitis (AS). Material and methods. Three hundred and ninety-four patients with clinical suspicion of spondyloarthritis sent for identification of HLA-B*27 gene were analyzed. One hundred and nineteen (30.2%) had confirmed the diagnosis of spondyloarthritis according to the ASAS criteria. The remaining 275 (69.8%) were used as controls. The identification of HLA-B*27 gene was performed using the PCR-SSOP method. The identification of the antigens of the ABO, Secretor and Lewis histo-blood systems was performed using hemagglutination and PCR-RFLP methods. The exact Fisher's test, the chi-square, and the values of Odds Ratio (OR) and Confidence Interval set at 95% were calculated using the GraphPad INSTAT software, accepting the error of 5%. Results. No statistically significant differences were observed in the frequency of antigenic profiles of ABO (χ2: 1.152; p = 0.764; GL: 3), Secreto (χ2: 0.779; p = 0.377; GL: 1) and Lewis (χ2: 1.853; p = 0.396; GL: 2) histo-blood groups between patients and controls. The Lea antigen was more frequent in patients with AS compared to controls (OR: 1.833; 95% CI: 1025- 3284, p = 0.053). This antigen was strongly associated with AS in HLA-B*27 negative patients compared to controls (OR: 4.469; 95% CI: 1931-10342; p = 0.0007). This association remained only in males in the absence of HLA-B*27 gene (OR: 6.880; 95% CI: 1852-25564; p = 0.004). Conclusions. AS is associated to the Lea antigen in HLAB* 27 negative male patients.
Introdução. As espondiloartrites compreendem um grupo de doenças fortemente associadas ao gene HLA-B*27. Tem sido proposto que genes não pertencentes ao complexo principal de histocompatibilidade humano influenciam a gênese destas doenças especialmente nos pacientes HLA-B*27 negativos. Objetivos. O objetivo deste estudo foi testar a hipótese de que os antígenos dos sistemas histo-sanguíneos ABO, Secretor e Lewis estão associados à espondiloartrites, especialmente a espondilite anquilosante (EA). Material e método. Foram analisados 394 pacientes com suspeita clínica de espondiloartrites encaminhados para identificação do gene HLA-B*27. Cento e dezenove (30,2%) tiveram o diagnóstico de espondiloartrite confirmado de acordo com os critérios ASAS. Os 275 (69,8%) restantes compuseram o grupo controle. A identificação do gene HLA-B*27 foi realizada com o uso do método PCR-SSOP. A caracterização dos antígenos dos sistemas histo-sanguíneos ABO, Secretor e Lewis foi realizada com o uso dos métodos hemaglutinação e PCR-RFLP. O teste exato de Fisher, o qui-quadrado, os valores de Odds Ratio (OR) e do intervalo de confiança a 95% foram calculados com o uso do software GraphPad Instat, aceitando o erro de 5%. Resultados. Não foram observadas diferenças estatisticamente significantes nas frequências dos perfis antigênicos dos sistemas histo-sanguíneos ABO (χ2: 1.152; p=0,764; GL: 3), Secretor (χ2: 0.779; p=0,377; GL: 1) e Lewis (χ2: 1.853; p=0,396; GL: 2) de pacientes e controles. Foi observada maior frequência do antígeno Lea em pacientes com EA, comparados aos controles (OR: 1.833; IC 95%: 1.025 – 3.284; p=0,053). Este antígeno mostrou-se fortemente associado à EA em pacientes HLA-B*27 negativos comparados aos controles (OR: 4.469; IC 95%: 1.931 – 10.342; p=0,0007). Esta associação se manteve apenas no gênero masculino na ausência do gene HLA-B*27 (OR: 6.880; IC 95%: 1.852 – 25.564; p = 0,004). Conclusões. A EA está associada ao antígeno Lea nos pacientes masculinos HLA-B*27 negativos.

This project involved the study of Lewis and related blood group glycosphingolipid isolated from individuals with normal and aberrant Lewis/secretor phenotypes. The objective was to find a biochemical basis for the unusual expression of Lewis and secretor phenotypes in Polynesians and to use this information to shed light on the "normal" expression of Lewis antigens. By using purified glycolipids, presenting them in the cell free environment of thin layer chromatography to Lewis antibodies and by determining structures by mass spectrometry it has been shown that: l. The Lec epitope is a terminal Galβ1-3Gal sequence, and not an internal branch as proposed by Hanfland (Hanfland et a1.,1986). 2. Lec or H-5-1 are present in Lewis negative phenotypes and their consequent consumption by the Le and ,Se transferases resulting in the known Lea and Leb antigens can be seen in the Lewis positives. 3. Phenotypically Le(a-b-) individuals have small amounts of Lewis antigens. This clearly demonstrates that although the Lewis negative phenotype exists at the crude serological level, this phenotype is not an "all-or-nothing" phenomenon at the chemical level. This also allows it to be postulated that the le gene is probably partially active. 4. Le(a+b+) individuals have both Lea and Leb glycolipids in the erythrocyte membrane and in plasma. Observed phenotyping anomalies appear to be related to there being quantitatively less Leb-6 in the Polynesian Le(a+b+) erythrocyte membrane than in the Le(a-b+) membrane. 5. The Le(a+b-) phenotype of Polynesians is actually the Le(a+b+) phenotype but with serologically undetectable Leb. This allows it to be postulated that the nonsecretor gene (se) is absent in Polynesians. 6. Extended structures are present in most of the Polynesian samples which is in support of a postulated weak secretor gene (Sew). It now appears that the difference between the extended Lewis glycolipids of Caucasians and Polynesians is quantitative. The postulated, Sew transferase appears to be inefficient and allows for increased formation of elongated glycoconjugates (polyglycosylceramides) to result. 7. Reduced fucosyltransferase activity allows increased elongation of the precursor chain to occur, which allows it to be postulated that fucosylation of the precursor prevents, or at least markedly reduces, chain elongation. It is speculated that, as almost everyone is either Lewis and/or secretor positive, perhaps the prevention of chain elongation is a biological reason as to why the Lewis and Secretor polymorphisms exist. 8. Differences in ceramide patterns of Lewis active glycolipids suggests that the small intestinal tract is not the only origin of plasma glycolipids, or there is differential absorption. 9. There is no plasma glycolipid-based reason for there being increased H type 2 antigen reactivity in the Polynesian erythrocyte membrane, nor a reason for the H antigen association with the Le(a+b+) phenotype.

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Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP
Introduction: Chagas disease is caused by the protozoan Trypanosoma cruzi, which is transmitted to humans commonly in the feces of a hemipterous popularly known as barber. The natural infection occurs mainly in childhood. After a period of approximately two decades infected individuals develop clinical manifestations such as Chagas heart disease and Chagas gastrointestinal disease (Megaesophagus and/or Megacolon). The expression of the antigens belonging to histo-blood systems ABO, Secretor and Lewis, controlled by the genes ABO (9q34.1), FUT2 (19q13.3) and FUT3 (19p13.3) differs between the organs affected by Chagas disease. It is possible that the differential tissue expression of ABO, Secretor and Lewis histo-blood groups influences the clinical manifestations of Chagas disease. Aim: The aim if this study was to verify if the antigens of the histo-blood systems ABO, Secretor and Lewis are associated with different clinical forms of Chagas disease. Materials and methods: After obtaining the informed consent peripheral blood and serum samples from 827 individuals were collected. Patients were divided into three subgroups according to their clinical state (megacólon [n=66], megaesophagus [n=119] and cardiomyopathy [n=154]). The control group consisted of 488 blood donors properly fit for the donation. The Lewis and ABO phenotyping were performed by hemagglutination test tube and gel columns agglutination, respectively. The IgG anti-T. cruzi antibodies were identified by ELISA. FUT2 and FUT3 genotyping were carried out by PCR-RFLP. Results: The mean age of patients with Chagas disease was 64.8±11.2 and blood donors 34.3±11.0 (p<0.0001). The differences between the percentages of the sex of the patients and donors were statistically significant (p <0.0001). The frequencies of ABO, Secretor and Lewis distributed in the three forms of the disease compared with each other and with donors, did not give differences statistically significant. The comparison between the ABO and Secretor combined, according to the three forms of Chagas disease, showed statistically significant differences for megaesophagus form (p=0.015). The frequencies of ABO, Secretor and Lewis antigen profiles between patients and donors showed differences statistically significant in favor of BLeb antigen (p=0.032). Conclusion: The results suggest that the high expression of antigen B, which characterizes the B and AB blood groups under the control of functional FUT2 (Secretor) gene acts as a risk factor for megaesophagus form of the Chagas disease.
Introdução: A doença de Chagas é causada pelo protozoário Trypanosoma cruzi, o qual é transmitido ao homem, comumente, pelas fezes de um hemíptero conhecido popularmente como barbeiro. A infecção natural ocorre principalmente na infância e após um período aproximado de duas décadas, parte dos indivíduos infectados desenvolvem manifestações clínicas como a Cardiopatia Chagásica Crônica e a doença do trato gastrointestinal (Megaesôfago e/ou Megacólon). A expressão dos antígenos dos sistemas histo-sanguíneos ABO, Secretor e Lewis, controlada pelos genes ABO (9q34.1), FUT2 (19q13.3) e FUT3 (19p13.3), difere entre os órgãos acometidos por esta doença e pode influenciar suas manifestações clínicas. Objetivo: Avaliar se os antígenos dos sistemas histo-sanguíneos ABO, Secretor e Lewis estão associados às diferentes formas clínicas da Doença de Chagas. Materiais e Métodos: Após a entrevista e obtenção do termo de consentimento livre e esclarecido, amostras de sangue periférico e soro de 827 indivíduos foram analisadas. Os pacientes com a forma crônica da Doença de Chagas foram divididos em três subgrupos de acordo com a forma clínica, (megacólon=66, megaesôfago=119 e cardiomiopatia=154). O grupo controle constitui-se de 488 doadores de sangue devidamente aptos à doação. As fenotipagens ABO e Lewis foram realizadas por métodos de hemaglutinação em tubos e colunas de gel, respectivamente. A pesquisa de anticorpos da classe IgG anti-T. cruzi foi realizada pelo teste de ELISA. Os genótipos FUT2 e FUT3 foram identificados por PCR-RFLP. Resultados: A média de idade dos pacientes chagásicos foi de 64,8±11,2 e dos doadores de sangue 34,3±11,0 (p<0.0001). As diferenças entre as porcentagens do sexo dos pacientes e doadores foram estatisticamente significantes (p< 0.0001). As frequências dos fenótipos ABO, Secretor e Lewis distribuídos nas três formas da doença comparados entre si e com os doadores, não revelaram diferenças estatisticamente significantes. A comparação entre os fenótipos ABO e Secretor combinados, de acordo com as três formas da Doença de Chagas, mostrou diferenças estatisticamente significantes para a forma megaesôfago (p=0,015). A comparação entre as frequências dos perfis antigênicos de pacientes e doadores, revelaram diferença estatisticamente significante para o perfil de antígenos BLeb (p=0,032). Conclusões: Os resultados sugerem que a expressão do antígeno carboidrato B, o qual caracteriza os grupos sanguíneos B e AB, cuja síntese está sob o controle dos genes funcionais FUT2 (Secretor), atua como um fator de risco para a forma megaesôfago da Doença de Chagas.

Uvod: Pojam "sekretor” ili „nesekretor" se odnosi na sposobnost pojedinca da luči antigene krvnih grupa ABO sistema u telesnim tečnostima. Određivanje ABO krvne grupe i sekretornog statusa, testom inhibicije hemaglutinacije pljuvačke i Lewis fenotipa na eritrocitima su važni u kliničkoj i forenzičkoj medicini, u odnosu na etiopatogenezu mnogih bolesti. Nesekretorstvo ABO krvnogrupne supstance je udruženo sa češćom pojavom autoimunih inflamatornih oboljenja među kojima su i seronegativne spondiloartropatije. Veća učestalost seronegativnih spondiloartropatija među osobama koje imaju HLA-B27 antigen predstavlja polaznu osnovu stanovišta da genetski faktori u kombinaciji sa faktorima sredine utiču na pojavu seronegativnih spondiloartropatija u genetski predisponiranih individua. Teza istražuje značaj testa inhibicije hemaglutinacije plijuvačke i određivanja ABO i Lewis fenotipa na eritrocitim u dijagnostici seronegativnih spondiloartropatija. Ciljevi i hipoteze: Cilj istraživanja je bio da se utvrdi učestalost nesekretora i sekretora ABO krvnogrupne supstance i Lewis fenotipa u grupi obolelih od seronegativnih spondiloartropatija i izvršiti poređenje rezultata u odnosu na grupu zdravih ispitanka. Pretpostavljeno je da postoji značajno veći broj nesekretora ABO krvnogrupne supstance u obolelih od seronegativnih spondiloartropatija u odnosu na zdrave ispitanike. Pretpostavljeno je i da postoji značajno veća učestalost nesekretora ABO krvnogrupne supstance u obolelih od seronegativnih spondiloartropatija sa negativnim HLA-B27 antigenom. Pretpostavljeno je da kod osoba obolelih od seronegativnih spondiloartropatija dolazi do promene Lewis fenotipa na eritrocitima u odnosu na sekretorni status u pljuvačci. Metode: Sprovedena je longitudinalna prospektibvna studija. Ispitanici stariji od šest godina oba pola podeljeni su u dve randomizovane grupe. Eksperimentalnu grupu sačinjavalo je 110 ispitanika sa dijagnozom oboljenja iz grupe seronegativnih spondiloartropatija. Kontrolnu grupu sačinjavalo je 103 dobrovoljna davaoca krvi, bez dijaghnoze oboljenja iz grupe seronegativnih spondiloartropatija. Ispitanicima kontrolne i eksperimentalne grupe određena je pripadnosti ABO krvnogrupnom sistemu, sekretorni status i Lewis fenotip, dok je osobama eksperimentalne grupe određen i fenotip HLA-B27. Uključujući kriterijumi osim navedenog bili su da ispitivane osobe ženskog pola nisu trudinice i da ispitanici obe grupe nisu primali transfuziju krvi tri meseca pre uključivanja u istraživanje. Rezultati: Rezultati istraživanja ukazuju da nesekretori ABO krvnogrupne supstance imaju 1,63 puta veći rizik (veću učestalost), oboljevanja od seronegativnih spondiloartropatija u odnosu na zdravu populaciju ispitanika, kao i da smanjena ekspresija Lewis (b) antigena predstavlja doprinoseći faktor razvoja seronegativnih spondiloartropatija. Ustanovljeno je da pod uticajem seronegativnih spondiloartropatija dolazi do izmene Lewis fenotipa na eritrocitima obolelih. Verovatnoća dokazivanja oboljenja iz grupe seronegativnih spondilartropatija među obolelima veća je za 11% kod nesekretora fenotipa HLA-B27- u odnosu na obolele nesekretore fenotipa HLA-B27+. Zaključak: Sekretorni status i Lewis fenotip predstavljaju zasebne dijagnostičke biohemijske markere nezavisne od HLA-B27 antigena koji doprinose ranijem otkrivanju osoba koje imaju predispoziciju razvoja oboljenja iz grupe seronegativnih spondiloartropatija.
Introduction:The term secretory state referes to ability of individual to secrete ABO blood group antigens in body fluids. Determination of the ABO blood group antigens and secretory status by hemagglutionation inhibition test using saliva as well as Lewis phenotype on erythrocytes are important in clinical and forensic medicine, in relation to the etiopathogenesis of many diseases. Non secretory status of ABO blood groupantegens is related with higher incidence of autoimmune inflammatory disease which include seronegative spondyloarthropathyes. Increased frequency of seronegative spondyloarthropathies among people who have the HLA-B27 antigen is starting point of the view that genetic factors in combination with environmental factors influence the occurence of seronegative spondyloarthropathies in genetically predisposed individuals. The tesis explores the significance of the hemagglutionation inhibition test of saliva and determination of ABO and Lewis antigens in diagnostics of seronegativespondyloarthropathyes. Goals and hypothesis: The aim of this study was to determine the frequency of non secretors and secretors of ABO blood group antigens and Lewis phenotype in a group of patient with seronegative spondyloarthropathies and make comparsion to the healthy examined group. It was assumed that there is a significantly higher number of non secretors of ABO blood group antigens among the patients with seronegative spondyloarthropathies compared to healthy examined persons. It was assumed that there is a significantly higher number of non secretors of ABO blood group antigens among the patients with seronegative spondyloarthropathies who do not have HLA-B27 antigen. It was assumed that in patients with seronegative spondyloarthropathies Lewis phenotype on erythrocits can be changed in relation to the secretory status in the saliva. Methods: We performed a prospective longitudinal study. Respondants older than six years of both gender were divided into two randomized groups. Experimental group is consisted of 110 patients diagnosed with seronegative spondyloarthropathy. The control group consisted of 103 blood donors who did not have diagnosed disease from the group of seronegative spondyloarthropathies. To the subjects of the control and experimental groups was determined ABO blood group antigens, secretory status and Lewis phenotype, while to the subjects of experimental group also was designated HLA-B27 phenotype. Including criteria other than the above were that among female respondants were not pregnant, and that both groups of respondants did not receive a blood transfusion three months before joining the study. Results: The resuts of the study showed that non secretors of ABO blood group antigens have a 1,63 times higher rise (higher incidence) of developing disease from the group of seronegative spondyloarthropathies compared to a healthy population of subjects, as well as that decreased expression of Lewis antigens (b) represents a contributing factor for development of seronegativespondyloarthropathies. It was found that under the influence of seronegative spondyloarthropathies there are changes in Lewis phenotype on erythrocytes of patients. It was found that under the influence of seronegative spondyloarthropathies there are changes in Lewis phenotype on erythrocytes of patients. Probability for confirmation seronegative spondyloarthropathies is higher for 11% among non secretors who have HLA-B27 negative phenotype in comparison to non secretors who have HLA-B27 positive phenotype. Conclusion: Secretory status and Lewis phenotype are separate diagnostic biochemical markers independent of HLA-B27 antigen that contribute to the early detection of people who have a predisposition of the disease from the group of seronegative spondyloarthropathies.

Les norovirus sont l'une des causes principales de gastroentérite. Depuis 2002, des variants de norovirus GII.4 successifs ont circulé dans la population par cycle de 2-3 ans, ce qui suscite des interrogations quant au rôle de leurs ligands, les antigènes tissulaires de groupes sanguins (HBGA), dans leur évolution. Nous avons analysé l'interaction entre des variants de GII.4 représentatifs et des HBGA, et déterminé le rôle d’acides aminés (aa) clés. Par mutagénèse dirigée, nous avons montré qu’une configuration stricte des aa directement impliqués dans l’accroche est indispensable. La suppression de la thréonine 395, caractéristique des variants après 2002, confère la capacité de se lier à Lex et Si-Lex, démontrant que les aa en dehors du site de liaison peuvent modifier les propriétés d’attachement. L'analyse de l'accroche de VLP de 6 variants isolés de 1987 à 2007 à des échantillons de salive phénotypés et des HBGA synthétiques montre que tous les variants sont capables de s’attacher à la salive des sécréteurs indépendamment du phénotype ABO et aux oligosaccharides propres au phénotype sécréteur. Deux variants récents ont pu également s’accrocher aux sucres présents dans la salive des nonsécréteurs Le(+). Nos données suggèrent que la capacité de se lier à Lex et Si-Lex serait une conséquence de la variation génétique des aa situés à proximité du site de liaison. L'analyse des propriétés d’attachement par résonance plasmonique de surface a montré que seuls les variants après 2002 présentent une affinité forte pour les antigènes A et B, suggérant que l’accélération évolutive des GII.4 pourrait être liée à une affinité accrue des variants pour les HBGA après 2002
Noroviruses are one of the leading causes of gastroenteritis worldwide. Since 2002 successive GII.4 variants have circulated in the population before being replaced every 2-3 years, which raises questions about the role of their histo-blood group antigen (HBGAs) receptors in their evolution. We analyzed the interaction between representative GII.4 variants and HBGAs and determined the role of selected amino acids (aa) in the binding profiles. By mutagenesis, we showed that there was a strict structural requirement for the aa directly implicated in HBGA bindings. The ablation of the threonine 395 residue, an epidemiological feature of the post 2002 variants, allowed to gain the capacity to bind to the Lewis x and sialyl-Lewis x antigens, demonstrating that aa residues outside the HBGA binding site can modify the binding properties. The analysis of the attachment of VLPs from 6 variants isolated from 1987 to 2007 to phenotyped saliva samples and synthetic HBGAs shows that all variants could attach to saliva of secretors irrespective of the ABO phenotype and to oligosaccharides characteristic of the secretor phenotype. Interestingly, two recent variants additionally bound to carbohydrates present in the saliva of Lewis-positive non-secretors. Our data suggest that GII.4 binding to Lex and Si-Lex antigens might be a by-product of the genetic variation of the aa located in the vicinity of the binding site. Analysis of the binding properties by surface plasmon resonance showed that only post 2002 variants presented a strong affinity for A and B antigens, suggesting that the GII.4 evolution could be related to an increased affinity for HBGAs for the post 2002 variants

The plasma concentration of factor VIII is influenced by the ABO blood group. Individuals with blood group 0 have a lower concentration of both factor VIII coagulant activity, factor VIII coagulant antigen (VIIICAg) and factor VIII related antigen (VIHRAg) than individuals with group A, B and AB. Thirty percent of the genetic variance of VIIIRAg concentration is due to the ABO blood group. The Lewis substances Lea and Leb are closely related to the A, B and H substances. We therefore examined the effect of the presence of these antigens on the plasma concentration of VIIICAg and VIIIRAg. The material was 74 monozygotic and 84 dizygotic twin pairs and 58 blood donors with ABO blood group 0. VIIICAg was determined by a radioimmunoassay and VIIIRAg was determined by an electroimmunoassay. A higher mean concentration °f VIIICAg (147%) and VIIIRAg (81%) was found in individuals with the Le antigen on their red cell surface compared to the mean concentration of VIIICAg (101%) and VIIIRAg (66%) in individuals who lacked this antigen. The difference was found in individuals with ABO blood group 0 only. Individuals with red cell Lea antigen are non-secretors and individuals who lack this antigen but have the Leb antigen are secretors of the A, B and H substances. The lowest factor VIII concentration was found in group 0 secretors. The effect of the Lewis phenotype on factor VIII concentration is therefore most probably due to an effect of the secretor locus. This finding may have practical implications for the diagnosis of carriers of hemophilia A. it has been shown that information on the ABO blood group improves the discrimination between carriers and normals. We found that the effect of ABO blood group on the total variance of VIIIRAg was higher in secretors (21%) than in non-secretors (8%). Since the frequency of secretors varies widely, it is possible that the importance of the ABO locus in carrier detection is different in different populations. Lewis blood typing in materials of carriers and normals are necessary to determine the effect of the Lewis phenotype in carrier detection.