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.     

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.     

Lewis a blood group antigen of non-secretors: a receptor for candida blastospores

This study tested the hypothesis that the Lewis a blood group antigen found predominantly on the cells of non-secretors might be one of the receptors for Candida species. Binding of strain 3118C to epithelial cells from either secretor or non-secretor donors was not inhibited by treating the cells with anti-Lewis a or anti-Lewis b antisera. Binding of strain 3091 to non-secretor cells was inhibited by pretreating the cells with anti-Lewis a, but this was not observed for secretor cells. The results suggest that Lewis a might be one of the receptors for some yeast strains.     

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.     

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.     

Secretor genotype (FUT2 gene) is strongly associated with the composition of Bifidobacteria in the human intestine

Intestinal microbiota plays an important role in human health, and its composition is determined by several factors, such as diet and host genotype. However, thus far it has remained unknown which host genes are determinants for the microbiota composition. We studied the diversity and abundance of dominant bacteria and bifidobacteria from the faecal samples of 71 healthy individuals. In this cohort, 14 were non-secretor individuals and the remainders were secretors. The secretor status is defined by the expression of the ABH and Lewis histo-blood group antigens in the intestinal mucus and other secretions. It is determined by fucosyltransferase 2 enzyme, encoded by the FUT2 gene. Non-functional enzyme resulting from a nonsense mutation in the FUT2 gene leads to the non-secretor phenotype. PCR-DGGE and qPCR methods were applied for the intestinal microbiota analysis. Principal component analysis of bifidobacterial DGGE profiles showed that the samples of non-secretor individuals formed a separate cluster within the secretor samples. Moreover, bifidobacterial diversity (p<0.0001), richness (p<0.0003), and abundance (p<0.05) were significantly reduced in the samples from the non-secretor individuals as compared with those from the secretor individuals. The non-secretor individuals lacked, or were rarely colonized by, several genotypes related to B. bifidum, B. adolescentis and B. catenulatum/pseudocatenulatum. In contrast to bifidobacteria, several bacterial genotypes were more common and the richness (p<0.04) of dominant bacteria as detected by PCR-DGGE was higher in the non-secretor individuals than in the secretor individuals. We showed that the diversity and composition of the human bifidobacterial population is strongly associated with the histo-blood group ABH secretor/non-secretor status, which consequently appears to be one of the host genetic determinants for the composition of the intestinal microbiota. This association can be explained by the difference between the secretor and non-secretor individuals in their expression of ABH and Lewis glycan epitopes in the mucosa.     

Lewis a blood group antigen of non-secretors: a receptor for candida blastospores

Abstract This study tested the hypothesis that the Lewis ^a blood group antigen found predominantly on the cells of non-secretors might be one of the receptors for Candida species. Binding of strain 3118C to epithelial cells from either secretor or non-secretor donors was not inhibited by treating the cells with anti-Lewis ^a or anti-Lewis ^b antisera. Binding of strain 3091 to non-secretor cell was inhibited by pretreating the cells with anti-Lewis ^a, but this was not observed for secretor cells.
The results suggest that Lewis ^a might be one of the receptors for some yeast strains.     

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.     

Effect of host Lewis and ABO blood group antigen expression on Helicobacter pylori colonisation density and the consequent inflammatory response

The Lewis^b blood group antigen has been implicated as a putative receptor for Helicobacter pylori in the gastric mucosa. Furthermore, an increased prevalence of duodenal ulcer was found in non-secretors and it has been suggested that secretor status may influence bacterial colonisation density. Other investigators have hypothesised that severity of antral gastritis may be related to colonisation density of the bacterium alone, and that a critical bacterial load is necessary for the development of duodenal ulcer. Our objectives were to investigate whether a relationship existed between host Lewis and ABO blood group phenotype and prevalence of H. pylori infection. In addition we investigated whether bacterial colonisation density and the ensuing inflammatory response was influenced by secretor status and ABO blood group phenotype. The Lewis and ABO blood group phenotype of 207 patients undergoing upper endoscopy was determined. Of these, 136 were secretors and 62 were non-secretors. Forty-five percent of patients were infected with H. pylori. No significant association was found between H. pylori infection and expression of Lewis^a or Lewis^b blood group antigen. The mean histological density of H. pylori was 1.8±0.2 among non-secretors and 1.51±0.13 among secretors (P=0.209), with a mean grade of lymphocytic infiltration significantly greater in H. pylori-infected non-secretors (2.23±0.123 vs 1.8±0.074; P=0.003). In addition, blood group O non-secretors had a significantly higher grade of lymphocyte infiltration of their gastric mucosa compared to non-O non-secretors (2.53±0.133 vs 1.93±0.181, P=0.027). These results suggest that although no in vivo relationship exists between H. pylori and preferential adhesion to the putative Lewis^b receptor, bacterial colonisation and the ensuing inflammatory response may be influenced at least in part by host expression of ABO and Lewis^a blood group antigens.     

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.     

Structural characterization of neutral oligosaccharides of human H+Leb+ gastric mucin

The structure of carbohydrate chains of human gastric mucin was investigated. The mucin, purified from pronase-degraded gastric aspirates of the secretors with blood group H+Leb, was subjected to alkaline borohydride treatment and a heterogeneous population of neutral (72.1%) and acidic (27.9%) oligosaccharide alditols was obtained. Ten oligosaccharides (I-X), representing 80.3% of the neutral oligosaccharide fraction, have been purified to homogeneity and their structures determined. These oligosaccharides ranged in length from 4 to 12 sugar units and contained mono-, bi-, and triantennary structures. Based on hemagglutination inhibition data in H-anti-H, Leb-anti-Leb, and I-anti-I systems, and the results of structural analyses, we proposed the following structures for these oligosaccharides: (formula, see text)     

Invasibility of Nectarless Flowers in Plant–Pollinator Systems

This paper considers plant–pollinator systems in which plants are divided into two categories: The plants that secret a substantial volume of nectar in their flowers are called secretors, while those without secreting nectar are called nonsecretors (cheaters). The interaction between pollinators and secretors is mutualistic, while the interaction between pollinators and nonsecretors is parasitic. Both interactions can be described by Beddington–DeAngelis functional responses. Using dynamical systems theory, we show global dynamics of a pollinator–secretor–cheater model and demonstrate mechanisms by which nectarless flowers/nonsecretors can invade the pollinator–secretor system and by which the three species could coexist. We define a threshold in the nonsecretors’ efficiency in translating pollinator–cheater interaction into fitness, which is determined by parameters (factors) in the systems. When their efficiency is above the threshold, non-secretors can invade the pollinator–secretor system. While the nonsecretors’ invasion often leads to their persistence in pollinator–secretor systems, the model demonstrates situations in which the non-secretors’ invasion can drive secretors into extinction, which consequently leads to extinction of the nonsecretors themselves.     

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.     

Oligosaccharides from feces of preterm infants fed on breast milk

Nine neutral and five acidic oligosaccharides were isolated from feces of a preterm (30th postmenstrual week) blood group A nonsecretor infant fed on pooled breast milk. Structural analyses were carried out using sugar and methylation analyses, fast atom bombardment mass spectrometry, and 1H NMR. The acidic oligosaccharides are well-known components of human milk. The neutral oligosaccharides are characteristic of nonsecretor milk. Surprisingly, no secretor gene-dependent oligosaccharides were present in the feces. Another preterm (27th postmenstrual week) blood group A, secretor infant fed on pooled breast milk showed the same fecal oligosaccharide pattern as above during the first week after birth, despite being a secretor individual. Also notable was the absence of blood group A-active oligosaccharides in this sample. Another sample of feces collected 8 weeks later from the latter infant contained the expected blood group A-active oligosaccharides. Furthermore, free sialic acid was present at the cost of the sialyl oligosaccharides seen earlier. Thus, infants born prematurely do not show the same degree of development of oligosaccharide metabolism as their more mature counterparts.     

Structures of neutral oligosaccharides isolated from the respiratory mucins of a non-secretor (O, Le(a+b-)) patient suffering from chronic bronchitis.

Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitis patient with blood group O, Le(a+b-). Oligosaccharides were released by alkaline-borohydride treatment and purified by anion-exchange chromatography, size exclusion chromatography, and HPLC on a silica-bonded alkylamine column. Structural studies employed 500-MHz 1H-NMR spectroscopy, fast-atom-bombardment mass spectrometry and methylation analysis. Twenty-four neutral oligosaccharides, ranging in size from disaccharides to hexasaccharides, were fully characterized in this study. None of the structures contained an alpha(1----2)-linked fucose residue, in keeping with the non-secretor status of the patient. Seven of the structures had fucose present in alpha(1----3)-linkage in the X-determinant, while only one oligosaccharide (compound 14b) was seen with fucose alpha(1----4)-linked in the Le(a) determinant. The following eight structures isolated from the mucins of the non-secretor patient had not been found previously in the mucins of secretor individuals: [formula: see text] This study confirms that the blood group status of an individual is reflected in the carbohydrate structures of the secreted mucins. Furthermore, it clearly illustrates the need for detailed carbohydrate structural studies of mucins from different individuals before any attempt can be made to correlate observed differences in oligosaccharide profiles to disease status.     

Structures of the neutral oligosaccharides isolated from A-active human gastric mucin

Alkaline borohydride reductive cleavage of the mucin, purified from gastric aspirates of the secretors with blood group A, resulted in a heterogeneous population of neutral (79.7%) and acidic (20.3%) oligosaccharide alditols. Nine oligosaccharides (I-IX), ranging from 6 to 15 sugar units, have been purified from the neutral oligosaccharide fraction. Based on the results of immunological assays, sugar composition, degradation with specific exoglycosidases, and methylation analyses, we propose the following structures for these oligosaccharides: (sequence in text)     

Urinary excretion of oligosaccharides induced by galactose given orally or intravenously

The effect of oral administration of galactose, lactose, and sucrose and intravenous injection of galactose on the urinary excretion of blood-group-active oligosaccharides has been studied. Galactose given either as the free sugar, a glycoside (lactose) or a constituent of normal diet was an absolute requirement for the formation and excretion of A-trisaccharide, B-trisaccharide and 2'-fucosylgalactose in blood group A, B and O(H) secretors, respectively. Great individual variation was seen in the amounts of galactose-dependent oligosaccharides excreted. Injection of galactose resulted in excretion of 3-59% of the amount of oligosaccharide formed after oral administration to the same individual. The mean ratio A-trisaccharide/B-trisaccharide was 2.7 in four blood-group-A1B secretors and 0.22 in three A2B secretors and can thus serve as a parameter for chemical differentiation between the two blood groups. The excretion of larger blood-group-active oligosaccharides, including the A-pentasaccharide, the B-pentasaccharide and lactodifucotetraose, that are normal components in urine from, respectively, starved A, B, and H secretors, was about the same after oral administration of galactose or lactose. The B-trisaccharide was the only oligosaccharide detected in plasma after oral galactose administration to a blood-group-B secretor individual. The concentration was 0.38 mg/l of plasma.     

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