Frequencies of secretors and non-secretors of ABH group substances among 1,000 alcoholic patients

The ABO blood group and secretor status of 1,000 alcoholic patients has been determined. The patients were drawn from large alcoholic units in the London area together with several small units, including rehabilitation centres, nd 127 were from Aberdeen.The findings have been compared with appropriate controls which take into account the ethnic origin of the patients in the series. A striking disturbance of the secretor/non-secretor ratio among group A patients compared with the controls is observed. There is an increase in group A non-secretors, which is almost exactly balanced by a loss of group A secretors so that the overall frequency of the group A phenotype is not disturbed. It is difficult to find an acceptable explanation for these results.     

Comparison of oligosaccharides derived from salivary mucin of Japanese secretor and non-secretor individuals of blood group type-A

Comparison of oligosaccharide components derived from salivary mucin was performed between secretor and non-secretor individuals. Salivary mucin was collected from four secretors and three non-secretors having blood group type-A. Compositional analysis showed that the contents of galactose and N-acetylglucosamine in the non-secretor were higher than those in the secretor. The O-linked oligosaccharides obtained by treatment with alkaline borohydride were separated by gel filtration using Sephadex G-50. The results indicated that the size of the type-A active oligosaccharides from the secretor was similar to or smaller than that of the non-secretor. Ion-exchange chromatography showed that the secretors had strong type-A activities in both the neutral and acidic fractions but the non-secretors showed type-A activity mainly in the neutral fraction. These results suggest that compositional differences in blood group substances exist between secretors and non-secretors.     

Non-secretion of blood group antigens and susceptibility to infection by Candida species

One of the innate defences against superficial infections by Candida species appears to be the ability of an individual to secrete the water-soluble form of his ABO blood group antigens into body fluids. There was a significantly higher number of non-secretors (48.9%) among 174 patients with either oral or vaginal candida infections compared with the proportion of non-secretors in the local population (26.6%). The protective effect afforded by the secretor gene might be due to the ability of glycocompounds in the body fluids of secretors to inhibit adhesins on the surface of the yeast. In attachment studies, preincubation of blastospores with boiled secretor saliva significantly reduced their ability to bind to epithelial cells. Non-secretor saliva did not reduce the binding and often enhanced the numbers of attached yeasts. Possible host-parasite interactions underlying the susceptibility of non-secretors to candida and other infections are discussed.     

Non-secretion of blood group antigens and susceptibility to infection by Candida species

Abstract One of the innate defences against superficial infections by Candida species appears to be the ability of an individual to secrete the water-soluble form of his ABO blood group antigens into body fluids. There was a significantly higher number of non-secretors (48.9%) among 174 patients with either oral or vaginal candida infections compared with the proportion of non-secretors in the local population (26.6%).
The protective effect afforded by the secretor gene might be due to the ability of glycocompounds in the body fluids of secretors to inhibit adhesins on the surface of the yeast. In attachment studies, preincubation of blastospores with boiled secretor saliva significantly reduced their ability to bind to epithelial cells. Non-secretor saliva did not reduce the binding and often enhanced the numbers of attached yeasts.
Possible host-parasite interactions underlying the susceptibility of non-secretors to candida and other infections are discussed.     

Lewis phenotypes and secretor character in the "Castilla la Nueva"-region (Spain). ABH and Lewis antigen levels in salivary secretion

In 1980 blood and saliva samples were taken from Spanish students of the University of Madrid. Red cells were analysed for A1B2BO and Lewis blood groups. Saliva samples were tested to detect the specific group substances ABH, Lea and Leb. A slightly higher frequency of the "le" gene (0.419) was found in our sample as compared to other Spanish samples. The phenotype frequencies of ABH secretors (77.2%) and non-secretors (22.8%) are in the range of other European populations. The levels of A and B antigens of individuals belonging to these blood groups were similar, whereas the average titration of the H substance showed the relation O greater than A2 greater than A1 greater than A1B greater than B. Analysis of variance proved this heterogeneity to be statistically significant. The amount of Lea substance in non-secretors was higher than in secretors. This shows again that the ABH secretor status has some influence on the quantity of this antigen. The average titration of the Leb substance in secretors was higher than that of Lea in individuals belonging to O, A and AB blood groups, but not in those with blood group B.     

Faecal Microbiota Composition in Adults Is Associated with the FUT2 Gene Determining the Secretor Status

The human intestine is colonised with highly diverse and individually defined microbiota, which likely has an impact on the host well-being. Drivers of the individual variation in the microbiota compositions are multifactorial and include environmental, host and dietary factors. We studied the impact of the host secretor status, encoded by fucosyltransferase 2 (FUT2) -gene, on the intestinal microbiota composition. Secretor status determines the expression of the ABH and Lewis histo-blood group antigens in the intestinal mucosa. The study population was comprised of 14 non-secretor (FUT2 rs601338 genotype AA) and 57 secretor (genotypes GG and AG) adult individuals of western European descent. Intestinal microbiota was analyzed by PCR-DGGE and for a subset of 12 non-secretor subjects and 12 secretor subjects additionally by the 16S rRNA gene pyrosequencing and the HITChip phylogenetic microarray analysis. All three methods showed distinct clustering of the intestinal microbiota and significant differences in abundances of several taxa representing dominant microbiota between the non-secretors and the secretors as well as between the FUT2 genotypes. In addition, the non-secretors had lower species richness than the secretors. The soft clustering of microbiota into enterotypes (ET) 1 and 3 showed that the non-secretors had a higher probability of belonging to ET1 and the secretors to ET3. Our study shows that secretor status and FUT2 polymorphism are associated with the composition of human intestinal microbiota, and appears thus to be one of the key drivers affecting the individual variation of human intestinal microbiota.     

Role of Mucin Lewis Status in Resistance to Helicobacter pylori Infection in Pediatric Patients

Background: Helicobacter pylori causes gastritis, peptic ulcer and is a risk factor for adenocarcinoma and lymphoma of the stomach. Gastric mucins, carrying highly diverse carbohydrate structures, present functional binding sites for H. pylori and may play a role in pathogenesis. However, little information is available regarding gastric mucin in children with and without stomach diseases. Materials and Methods: Expression of mucins and glycosylation was studied by immunohistochemistry on gastric biopsies from 51 children with and without H. pylori infection and/or peptic ulcer disease. Results: In all children, MUC5AC was present in the surface epithelium and MUC6 in the glands. No MUC6 in the surface epithelium or MUC2 was detected in any section. The Le^b and Le^a blood group antigens were present in the surface epithelium of 80% and 29% of children, respectively. H. pylori load was higher in Le^b negative children than in Le^b positive individuals (mean ± SEM 17.8 ± 3.5 vs 10.8 ± 1.5; p < 0.05), but there was no correlation between Le^a or Le^b status and gastritis, nodularity, and gastric or duodenal ulcer (DU). Expression of sialyl‐Le^x was associated with H. pylori infection, and DU. Conclusions: Mucin expression and glycosylation is similar in children and adults. However, in contrast to adults, pediatric H. pylori infection is not accompanied by aberrant expression of MUC6 or MUC2. Furthermore, the lower H. pylori density in Le^b positive children indicates that H. pylori is suppressed in the presence of gastric mucins decorated with Le^b, the binding site of the H. pylori BabA adhesin.     

Examining the presence of ABO(H) antigens of blood types in the saliva of patients with oral cancer

Number of researches dealing with the influence of the ABO blood group antigens on the development of the oral cancer have hypothesized that people who do not secrete these substances in the saliva are more prone to suffer from this disease. The objective of this research is to examine this hypothesis. In total 114 subjects were examined, half of which suffered from oral cancer, while the other half was the healthy control group. All examinees were subjected to clinical examinations and the experimental group to pathohistological examination. An analysis of the secretor status was carried out using the Wiener agglutination test. The experimental group consisted of 78.95% of secretors, while the control group consisted of 82.46% of secretors. This difference is not statistically significant. The starting hypothesis that non-secretors are more prone to the development of oral cancer was not confirmed.     

Inhibitory effect of saliva from secretors and non-secretors on binding of meningococci to epithelial cells

Abstract Carriage of Neisseria meningitidis B:4:P1.15 was higher among non-secretors during a school outbreak of meningitis; non-secretors had lower levels of anti-meningococcal salivary IgM. Flow cytometry was used to assess effects of secretor and non-secretor saliva on binding of B:4:P1.15 to buccal epithelial cells: (1) to assess inhibition by IgA and IgM; and (2) to assess contributions of salivary antibodies to inhibitory activities. Greater inhibition was obtained with secretor saliva: pooled ( P = 0.049); fresh ( P = 0.0001). Purified IgA ( P = 0.02) and IgM ( P = 0.03) were equally inhibitory. After absorption of anti-meningococcal antibodies, there was still significant inhibitory activity in the pools: secretors ( P = 0.018); non-secretors ( P = 0.005). These results indicate that both secretory immunoglobulins and other factors contribute to protection against colonisation by meningococci and might explain the increased carriage of B:4:P1.15 in this population.     

Secretion of fucosylated oligosaccharides related to the H antigen by human gastric cells

 Although the role of the blood group antigens in the gastrointestinal tract is not well understood, alterations in blood group-related antigens have been described in some pathological processes. Thus, the knowledge of their expression under normal conditions is of special interest. Those individuals expressing their ABO blood group in exocrine epithelia and secretions are called secretors. The aim of the present study was the localization of H antigen expression in the normal human gastric epithelial cells of non-O blood group individuals. For this, a monoclonal anti-H antibody was examined by immunocytochemical methods at both the light and electron microscopic levels. In combination with enzymatic and chemical treatments, the nature of the oligosaccharide chains containing the H antigen was characterized. The selected cases were four A secretors, three A non-secretors, and three B non-secretors. The labeling of the anti-H antibody in the human stomach is described, irrespective of the blood group of the individuals. The staining was abolished when O-linked oligosaccharides were removed. Since commercially available anti-H antibodies usually also recognize other H-related antigens, the labeling of the antibody by H-related antigens cannot be dismissed. Our findings suggest the existence of H or H-related antigens in the O-linked oligosaccharides of the secretory granules of the surface, gastric pit, mucous neck, and transitional cells of the fundic mucosa, and in the intracellular canaliculi and tubulovesicular system of parietal cells. The H or H-related antigens were also localized in the apical membrane of all the cell types of the epithelial cells of the human fundic mucosa. The overall distribution of the H or H-related antigens in the stomach in non-O blood group individuals suggests the constitutive expression of an α(1,2)fucosyltransferase. Received: 24 October 1997 / Accepted: 3 March 1998     

The Three-dimensional Structure of the Extracellular Adhesion Domain of the Sialic Acid-binding Adhesin SabA from Helicobacter pylori

The gastric pathogen Helicobacter pylori is a major cause of acute chronic gastritis and the development of stomach and duodenal ulcers. Chronic infection furthermore predisposes to the development of gastric cancer. Crucial to H. pylori survival within the hostile environment of the digestive system are the adhesins SabA and BabA; these molecules belong to the same protein family and permit the bacteria to bind tightly to sugar moieties Lewis^B and sialyl-Lewis^X, respectively, on the surface of epithelial cells lining the stomach and duodenum. To date, no representative SabA/BabA structure has been determined, hampering the development of strategies to eliminate persistent H. pylori infections that fail to respond to conventional therapy. Here, using x-ray crystallography, we show that the soluble extracellular adhesin domain of SabA shares distant similarity to the tetratricopeptide repeat fold family. The molecule broadly resembles a golf putter in shape, with the head region featuring a large cavity surrounded by loops that vary in sequence between different H. pylori strains. The N-terminal and C-terminal helices protrude at right angles from the head domain and together form a shaft that connects to a predicted outer membrane protein-like β-barrel trans-membrane domain. Using surface plasmon resonance, we were able to detect binding of the SabA adhesin domain to sialyl-Lewis^X and Lewis^X but not to Lewis^A, Lewis^B, or Lewis^Y. Substitution of the highly conserved glutamine residue 159 in the predicted ligand-binding pocket abrogates the binding of the SabA adhesin domain to sialyl-Lewis^X and Lewis^X. Taken together, these data suggest that the adhesin domain of SabA is sufficient in isolation for specific ligand binding.     

Helicobacter pylori infection can change the intensity of gastric Lewis antigen expressions differently between adults and children

This study tested whether there were different expressions of gastric Lewis antigens between children and adults with Helicobacter pylori infection, and whether the difference was related to the infection outcome. About 68 dyspeptic children and 110 dyspeptic adults were enrolled to check H. pylori infection, its colonization density, and the related histology. Gastric Lewis antigens b (Le^b), x (Le^x), and sialyl-Lewis x (sialyl-Le^x) were immunohistochemically stained and scored for the intensity. The H. pylori-infected adults, but not the children, had a lower Le^b intensity over the antrum (p = 0.019) but higher Le^b intensity over the corpus (p = 0.001) than the non-infected ones. Over the antrum, both the H. pylori-infected children and adults had a lower Le^x and higher sialyl-Le^x intensity than those non-infected ones (p < 0.05). The H. pylori-infected adults had a higher bacterial density (p = 0.004) and Le^b intensity (p = 0.016) over the corpus than the H. pylori-infected children. For the H. pylori-infected adults, but not children, the corpus had a higher Le^b (p = 0.038) and lower Le^x (p = 0.005) intensity than the antrum. Furthermore, the H. pylori-infected adults expressed a higher Le^b and had a higher bacterial density than those with weak Le^b (antrum, p < 0.001; corpus, p = 0.001). In conclusion, H. pylori infection is associated with the intensity change of Lewis antigen expressions in the stomach. The changes of gastric Lewis antigen expressions are different between adults and children with H. pylori infection, which may exert different H. pylori colonization over the corpus between adults and children.     

Role of ABO secretor status in mucosal innate immunity and H. pylori infection

The fucosylated ABH antigens, which constitute the molecular basis for the ABO blood group system, are also expressed in salivary secretions and gastrointestinal epithelia in individuals of positive secretor status; however, the biological function of the ABO blood group system is unknown. Gastric mucosa biopsies of 41 Rhesus monkeys originating from Southern Asia were analyzed by immunohistochemistry. A majority of these animals were found to be of blood group B and weak-secretor phenotype (i.e., expressing both Lewis a and Lewis b antigens), which are also common in South Asian human populations. A selected group of ten monkeys was inoculated with Helicobacter pylori and studied for changes in gastric mucosal glycosylation during a 10-month period. We observed a loss in mucosal fucosylation and concurrent induction and time-dependent dynamics in gastric mucosal sialylation (carbohydrate marker of inflammation), which affect H. pylori adhesion targets and thus modulate host-bacterial interactions. Of particular relevance, gastric mucosal density of H. pylori, gastritis, and sialylation were all higher in secretor individuals compared to weak-secretors, the latter being apparently "protected." These results demonstrate that the secretor status plays an intrinsic role in resistance to H. pylori infection and suggest that the fucosylated secretor ABH antigens constitute interactive members of the human and primate mucosal innate immune system.     

Comparison of human saliva and synthetic histo-blood group antigens usage as ligands in norovirus-like particle binding and blocking assays

Blocking of norovirus-like particle binding to their cellular ligands, histo-blood group antigens with immune sera, is considered a surrogate norovirus neutralization assay. We compared human secretor positive saliva and synthetic biotinylated carbohydrates as a source of histo-blood group antigens in binding and blocking assays. Six norovirus capsid-derived virus-like particles belonging to genogroup I (GI-1-2001 and GI-3-2002) and genogroup II (GII-4-1999, GII-4-2010 New Orleans, GII-4-2012 Sydney and GII-12-1998) noroviruses were produced by a recombinant baculovirus expression system and binding profile to saliva type A, B and O and to synthetic antigens (A trimer, B trimer, H type 1, H type 3, Lewis^a and Lewis^b) was identified. Good correlation between virus-like particle binding to saliva type A and synthetic A trimer (r = 0.66, p < 0.05) and saliva type B and synthetic B trimer (r = 0.75, p < 0.05) was observed. Binding of each norovirus virus-like particle to the selected histo-blood group antigens was blocked by convalescent sera from NoV-infected subjects or type-specific mouse antisera. Our results support the use of either saliva or synthetic antigens in blocking assay to measure the ability of norovirus antisera to block virus-like particle binding to the carbohydrate ligands.     

Non-secretion of ABO blood group antigens as a host susceptibility factor in the spondyloarthropathies.

Gram negative bacteria precipitate reactive arthritis and may be concerned in the pathogenesis of ankylosing spondylitis and other spondyloarthropathies. Susceptibility to many infectious agents is associated with ABO blood group or secretor state, or both. The distribution of the ABO blood group or secretor state, or both, was therefore determined in 87 patients with ankylosing spondylitis and 32 with other forms of spondyloarthropathy. The prevalence of non-secretors was significantly increased in the total patient group (54/114; 47%) and in the subgroup with ankylosing spondylitis (41/84; 49%) compared with local controls (89/334; 27%) (p less than 0.001). Other subgroups of patients showed a similarly increased prevalence of non-secretion (33-47%). The distribution of ABO blood groups did not differ between patients and controls. The association between non-secretor state and ankylosing spondylitis strengthens the hypothesis that ankylosing spondylitis is a form of reactive arthritis. It also suggests several pathogenic mechanisms which may be relevant to the initial hostparasite interaction in ankylosing spondylitis.     

ABO blood group,secretor state,and susceptibility to recurrent urinary tract infection in women.

ABO blood group and secretor state was determined in 319 women with recurrent urinary tract infection and compared with those of a control group of 334 women of similar age ranges. Women of blood groups B and AB who are non-secretors of blood group substances showed a significant relative risk of recurrent urinary tract infection of 3.12 (95% confidence limits, 1.49 and 6.52) in comparison with other types. This appears to be a genuine example of synergy in which absence of anti-B isohaemagglutinin and secretor substances combines to give an increased risk of recurrent urinary tract infection. Determination of blood group and secretor state may provide additional information in identifying those at risk.     

Characterization of anti-Leb antibody purified from serum of immunized rabbits.

An anti-Le(b) antibody was produced in sera of rabbits by immunization with human saliva from blood group O Le(a-b+) secretor and purified by sequential use of silica beads immobilized with H type 1, Le(a) and Le(b). The purified antibody agglutinated only Le(a-b+) red cells irrespective of their ABO blood type. Hemagglutination reaction with the antibody of blood group O Le(a-b+) red cells was inhibited not only by saliva samples from blood group Le(a-b+) secretors and Synsorb beads immobilized with Le(b) hapten, but also weakly by Synsorb immobilized with Y and H type 2 haptens.     

Red cell H-deficient,salivary ABH secretor phenotype of Reunion island. Genetic control of the expression of H antigen in the skin

Based on the genetic model proposing thatH andSe are two structural genes, we predicted that the red cell H-deficient, salivary ABH secretor phenotype should be found on Reunion island, where a large series of H-deficient non-secretor families have been previously described. Two such Reunion individuals are now reported. POU [A_h, Le(a–b+), secretor of A, H, Le^a and Le^b in saliva] and SOU [O_h, Le(a–b+), secretor of H, Le^a and Le^b in saliva]. Both are devoid of H -2-fucosyltransferase activity in serum. In addition, the preparation of total non-acid glycosphingolipids from plasma and red cells of POU revealed the type 1ALe^b heptaglycosylceramide and small amounts of the monofucosylated type 1 A hexaglycosylceramide. Both glycolipids possess an H structure probably synthesised by the product of theSe gene. No other blood group A glycolipids, with types 2, 3 or 4 chains, normally present in the presence of the product of theH gene, were found on red cells or plasma of POU.TheH,Se andLe genetic control of the expression of ABH and related antigens in different tissue structures of the skin is described in 54 H-normal individuals of known ABO, secretor and Lewis phenotypes; in one red cell H-deficient salivary secretor (SOU); and in one H-deficient non-secretor (FRA). Sweat glands express ABH under the control of theSe gene. Sweat ducts express ABH under the control of bothH andSe genes and Lewis antigens under the control ofLe and bothH andSe genes. Epidermis, vascular endothelium and red cells express ABH under the control of theH gene. The products ofH andSe genes are usually expressed in different cells. However, the results illustrate that in some structures, like the epithelial cells of sweat ducts, both the products ofH andSe genes can contribute to the synthesis of the same Le^b structure.     

Blood group antigen expression is involved in <Emphasis Type="Italic">C. albicans</Emphasis> interaction with buccal epithelial cells

Human blood group polymorphisms are known to be determined by the expression of A, B or H antigens and the Lewis antigens. Protection against microbial infections has been associated with inheritance of polymorphisms in genes encoding and regulating the expression of ABH and Lewis antigens in bodily secretions and epithelial tissue surfaces, subsequently resulting in the presentation of different glycosylated terminal antigens on the cell surface. We investigated the role of blood group antigens in diversifying the glycosylation of buccal epithelial cells (BEC) that line the oral cavity. Specifically, we characterized and statistically evaluated the expression of histo-blood group (A, B, O) antigens on N-and O-linked glycans from BEC membrane proteins of various individuals that represented different blood group type and secretor status using a porous graphitic carbon liquid chromatography electrospray ionization mass spectrometry (PGC-LC-ESI-MS) based glycomics approach. From these BEC membrane proteins a total of 77 N-glycan and 96 O-glycan structures were structurally characterized from 19 individuals and relatively quantitated. The N-glycans from the secretor individuals did not express any A/B blood group determinants, but contained several terminal H-antigens. Apart from the non-secretors, the N-glycan profiles of BEC from all blood groups displayed similar glycan types, while varying in their relative intensities between individuals. However, multivariate analysis of the O-glycans from individuals displayed segregation patterns clearly associated with their blood group type and secretor status. In adhesion assays the oral pathogen Candida albicans showed a significantly higher interaction to blood group O type BECs relative to other blood groups.