Secretor status and infection in patients with Graves' disease.

We have demonstrated that the inability to secrete the water soluble glycoprotein form of the ABO blood group antigens into saliva is significantly more common in patients with Graves' disease than control subjects (40% vs 27%: P less than 0.025) but not among those with Hashimoto's thyroiditis or spontaneous primary atrophic hypothyroidism. Non-secretion is associated with increased susceptibility to infection and to asymptomatic carriage of some microorganisms. Although Yersinia enterocolitica has been found to express antigen cross reactive with the TSH receptor, we did not find an increased prevalence of Yersinia species in the faeces of 107 patients with Graves' disease. The isolation rate (less than 1%) was similar to that observed in the local population with diarrhoeal illness. Salivary IgA levels determined by whole cell ELISA with Y. enterocolitica 03 were not elevated in the majority of specimens examined. The results suggest that in contrast to reports from Scandinavia, there is no strong evidence that yersiniae play a role in the pathogenesis of Graves' disease among patients in South east Scotland. Non-secretors are significantly over represented among patients with several other autoimmune diseases; however, with the exception of antitubulin antibodies, non-secretors with Graves' disease did not have more antibodies to other human antigens than secretor patients.

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

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:4:1.15 in this population.

Helicobacter pylori in the mouth--negative isolation from dental plaque and saliva.

OBJECTIVE: To determine the colonization of Helicobacter pylori in dental plaque and saliva of individuals with H. pylori-associated gastritis. PATIENTS AND METHODS: One hundred and twenty adult dyspeptic patients attending for outpatient endoscopy were randomly selected. Saliva, dental plaques and antral biopsies were collected and cultured in Dent's medium. Antral biopsies were also taken for histological confirmation of colonization. RESULTS: Eleven patients were withdrawn owing to poor tolerance of endoscopy. Fifty-two patients (47%) were found to be H. pylori positive on culture from antral biopsies and on antral histology. H. pylori was not isolated from saliva and dental plaques in any of the patients irrespective of their infective status. The H. pylori seropositivity rate was higher in the Japanese (72%) than in the Dutch (33%). CONCLUSION: We failed to isolate H. pylori from saliva and dental plaque in a group of dyspeptic patients with H. pylori-associated gastritis. We believe that our finding strongly suggests that oral to oral route is not an important mode of transmission in the adult population.

Assessment of Lewis blood group antigens and secretor status in autopsy specimens.

The ability of enzyme linked immunosorbent assays (ELISA) to detect Lewis and H antigens in secretions obtained from 280 autopsies was assessed. The ELISA results were compared with those for matched blood specimens examined by agglutination of erythrocytes by monoclonal anti-Lewis(a) and anti-Lewis(b) antibodies. There was good agreement between the results for the two tests and the ELISAs could be used to determine secretor status of the subject. While determination of ABO group with monoclonal anti-A and anti-B was possible even with lysed blood, the results for Lewis typing by erythrocyte agglutination were poor if the sample was lysed or partially lysed. Detection of the antigens by ELISA was as efficient among elderly subjects as among younger ones and both H and Lewis antigens could be detected on erythrocytes and in secretions up to 127 h after death.

Association between secretor status and respiratory viral illness.

OBJECTIVE: To determine whether non-secretion of blood group antigens is associated with respiratory virus diseases. DESIGN: Study of secretor status in patients with respiratory virus diseases determined by an enzyme linked immunosorbent assay (ELISA) developed to identify Lewis (Le) blood group antigen phenotypes (Le(a) non-secretor; Le(b) secretor). SUBJECTS: Patients aged 1 month to 90 years in hospital with respiratory virus diseases (584 nasal specimens). MAIN OUTCOME MEASURES: Criteria for validation of ELISA (congruence between results on ELISA testing of 1155 saliva samples from a previous study and previously established results on haemagglutination inhibition (HAI) testing, proportions of Le(a), Le(b), and Le- phenotypes in 872 samples of nasal washings from a previous study compared with the normal population). Secretor status of patients determined by ELISA and viruses isolated. RESULTS: Agreement between HAI and ELISA for 1155 saliva samples was 97%. Lewis antigens were detected by ELISA in 854 (97.9%) of nasal washings (Le(a) 233 (26.7%), Le(b) 621 (71.2%), and Le- 18 (2.1%)) in proportions predicted for a northern European population. Secretors were significantly overrepresented among patients from whom influenza viruses A and B (55/64, 86%; p less than 0.025), rhinoviruses (63/72, 88%; p less than 0.01), respiratory syncytial virus (97/109, 89%; p less than 0.0005), and echoviruses (44/44, p less than 0.0005) had been isolated compared with the distribution of secretors in the local population. CONCLUSION: Secretion of blood group antigens is associated with respiratory virus diseases.

The effect of Pseudomonas alginate on rat alveolar macrophage phagocytosis and bacterial opsonization.

Alginate obtained from a mucoid strain of Pseudomonas aeruginosa was shown to inhibit the phagocytosis of an isogenic non-mucoid revertant by rat alveolar macrophages. Phagocytosis of Staphylococcus albus, binding of sensitized sheep erythrocytes to Fc receptors and uptake of latex particles were also inhibited. These results suggest that the alginate acts as a barrier, surrounding the macrophage preventing the attachment of bacteria or other particles to the plasma membrane. This conclusion was supported by showing that alginic acid, a polysaccharide from seaweed structurally similar to alginate also inhibited the phagocytosis of non-mucoid Ps. aeruginosa. The alginate also inhibited opsonisation of the non-mucoid revertant by a non-agglutinating hyperimmune serum. It is proposed that alginate confers a selective advantage on mucoid producing forms of Ps. aeruginosa by impairing the host immune response by its action on alveolar macrophages and opsonization of bacteria.

Are 'new' antigenic determinants exposed on aggregated bovine serum albumin?

Antigenic specificities of native monomer, heat-denatured monomer and heat-polymerized BSA have been compared serologically. Distinct differences between monomer and polymer preparations were observed with respect to their ability to inhibit each other's binding to antibody and also between their respective rates of dissociation from immune complexes. While it would be possible to interpret the results in terms of the appearance of 'new' antigenic determinants on the polymerized antigen, the results are best explained by an enhanced capacity of polymerized BSA to establish polyvalent binding to antibody of low intrinsic affinity.

Inhibition of Helicobacter pylori haemagglutination activity by human salivary mucins.

Thirty isolates of Helicobacter pylori from gastric biopsies agglutinated human erythrocyte suspensions. Crude mucin preparations derived from saliva of 20 different donors were examined for their ability to inhibit haemagglutination. All mucin preparations exhibited strong inhibitory activity. Removal of sialic residues from mucin preparations by treatment with neuraminidase resulted in a substantial reduction of their inhibitory activity. The mucin preparations had no bactericidal or aggregation activity for H. pylori. These results are discussed in the context of the role of mucins in colonization of the gastric mucosa by H. pylori.

Semi-quantitative determination of H type 1 and type 2 antigens on buccal epithelial cells and in saliva of secretors and non-secretors.

The amount of H antigens on buccal epithelial cells (BEC) of secretors and non-secretors was measured by flow cytometry. H type 1 and H type 2 on BEC were detected with fluorescein-labelled Ulex europaeus lectin, and H type 2 was measured with mouse monoclonal antibody. Between 3.5 and 6 times more H antigen was detected on cells from secretors compared with cells from non-secretors. The level of H type 2 was the same on BEC of secretors and non-secretors. Adsorption of H type 1 antigen from secretor saliva onto non-secretors BEC was demonstrated. A simple and sensitive ELISA method was developed for the determination of H in saliva with biotin-labelled Ulex lectin. This system provides a simple means for measuring the amount of H present in saliva and for the determination of secretor status.

Secretor status and humoral immune responses to Neisseria lactamica and Neisseria meningitidis.

Non-secretors of ABO blood group antigens are over-represented among patients with meningococcal diseases. Lower levels of secretory IgA reported for non-secretors have been suggested to compromise mucosal defences. Total serum and salivary IgG, IgA and IgM and levels of these isotypes specific for Neisseria lactamica and five isolates of meningococci were determined by ELISA for 357 pupils and staff of a secondary school in which an outbreak of meningitis occurred. There were no differences in total or specific levels of serum IgG, IgA or IgM or salivary IgG or IgA of secretors compared with non-secretors. Non-secretors had significantly lower levels of salivary IgM (P = 0.022). A similar pattern was observed for levels of IgM specific for N. lactamica and five meningococcal isolates. The significance of these results is discussed with reference to the role of secretory IgM in protection of mucosal surfaces in infants.

Blood group, secretor status, and susceptibility to infection by Neisseria gonorrhoeae.

To determine whether the presence or absence of anti-B isohaemagglutinin in individuals of blood group B increases their susceptibility to gonococcal infections 567 new patients attending a sexually transmitted disease clinic were screened for blood group and secretor status. Of the patients with blood group B, 20.1% had gonorrhoea and 12% had not. A higher percentage (20.9%) of patients with no anti-B isohaemagglutinin had gonorrhoea compared with those without (12.1%). There was, however, no synergy between the absence of anti-B isohaemagglutin and nonsecretion of water-soluble blood group B antigen. Further research is needed to determine the underlying host-parasite interactions responsible for the increased susceptibility to gonorrhoea in these individuals.

Factors influencing oral carriage of yeasts among individuals with diabetes mellitus.

A total of 439 individuals with diabetes mellitus were examined for carriage of yeasts by the oral rinse and palatal swab techniques. Eighteen genetic or environment variables were assessed for their contribution to carriage of yeasts. The factor contributing to palatal and oral carriage of yeasts among individuals with insulin dependent diabetes mellitus (IDDM) was age (P < 0.01). The factor contributing to palatal carriage of yeasts among individuals with non-insulin dependent diabetes mellitus (NIDDM) was poor glycaemic control (glycosuria P < 0.01); carriage in the oral cavity as a whole was influenced additionally by non-secretion of ABH blood group antigens (P < 0.05). Introduction of a denture altered the above risk factors. For individuals with IDDM, oral carriage was associated with the presence of retinopathy (P < 0.05); palatal carriage was influenced by poor glycaemic control (HbA1P < 0.01, plasma glucose levels P < 0.05) and age (P < 0.05). For those with NIDDM, palatal carriage was associated with continuous presence of the denture in the mouth (P < 0.01); oral carriage was associated with plasma glucose levels (P < 0.05).

The Stonehouse study: secretor status and carriage of Neisseria species.

The genetically determined inability to secrete the water-soluble glycoprotein form of the ABO blood group antigens into saliva and other body fluids is a recognized risk factor for meningococcal disease. During a community-wide investigation of a prolonged outbreak of disease due to a B15:P1.16 sulphonamide-resistant strain of Neisseria meningitidis in Stonehouse, Gloucestershire (the Stonehouse survey), the ABO blood group and secretor status of almost 5000 residents was determined. The proportion of non-secretors in the Stonehouse population was significantly higher than the proportion of non-secretors among blood donors in the South West Region and in England generally. Seven of 13 Stonehouse residents with meningococcal disease who were tested were found to be non-secretors, a high proportion. The outbreak in Stonehouse cannot be explained solely in terms of the increased proportion of non-secretors. There was no clear correlation between the proportions of non-secretors in different areas within the town and the incidence of cases of meningococcal disease. Carriers of meningococci, whether outbreak or other strains, were not more likely to be non-secretors. The reasons why non-secretors are more susceptible to meningococcal disease remain to be determined, but they do not appear to be related to carriage of meningococci.

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.

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.

Chronic atrophic oral candidiasis among patients with diabetes mellitus--role of secretor status.

Non-diabetic individuals who are non-secretors of blood group antigens are prone to superficial infections by Candida albicans. In this study, 216 patients with diabetes mellitus who were denture wearers were examined for the presence or absence of denture stomatitis. There was an overall trend for non-secretors to be prone to denture stomatitis compared with secretors. Stepwise linear discriminant analysis was used to dissect the contribution of secretor status and other variables to the development of the disease. Secretor status was found to be a contributory factor among patients with non-insulin dependent diabetes but not among those with insulin-dependent diabetes. The possible reasons for this are discussed.