Human coproantibody secretory immunoglobulin A response to Yersinia species.

A semiquantitative indirect immunofluorescence assay to detect coproantibody secretory IgA (SIgA) was established to investigate the human intestinal immune response to Yersinia species. This assay was based on microagglutination of SIgA in fecal specimens with the patient's homologous organism. Two populations of patients were defined, those who produced an agglutinating (2+) SIgA response and those who did not. A comparison between SIgA production and standard in vitro virulence-related characteristics of infecting organisms, including autoagglutination, calcium dependence, plasmid carriage, and absorption of Congo red, mouse virulence, and clinical presentation, was performed. A positive (2+) SIgA result was associated with acute enteric illness (positive predictive value, 78.6%) and mouse virulence (positive predictive value, 85.7%). When patients with active inflammatory bowel disease were excluded, the positive predictive value of SIgA for mouse virulence and acute enteric disease became 100%. In addition to strains of Yersinia enterocolitica 4,O:3, strains generally characterized as nonpathogenic, including Yersinia frederiksenii, were found to be associated with acute disease, mouse virulence, and stimulation of SIgA. The indirect immunofluorescence assay for detection of SIgA response appears to be a useful indicator of pathogenic strains of yersiniae recovered from enteric specimens.     

Subclass distribution of salivary secretory immunoglobulin A antibodies to oral streptococci

The ability of specific secretory immunoglobulin A (S-IgA) antibodies to inhibit bacterial colonization of mucosal surfaces may be neutralized by the activity of bacterial IgA1 proteases. Because of the resistance of the IgA2 subclass to these enzymes, the biological effect of IgA1 proteases in vivo may depend on the subclass distribution of the bacterium-specific antibodies. We have estimated the subclass distribution of S-IgA antibodies in saliva samples from 13 individuals against IgA1 protease-producing (Streptococcus sanguis and Streptococcus oralis) and nonproducing (Streptococcus gordonii and Streptococcus mitis bv. 2) oral streptococci. IgA1 was found to be the predominant subclass of antibodies against these four bacteria in most of the saliva samples, corroborating previous data suggesting a role of IgA1 proteases in plaque formation. However, variation in the subclass distribution of S-IgA antibodies against the same strain was observed. In one individual, IgA2 was the predominant subclass of antibodies against all four streptococci and of total salivary S-IgA, pointing to the possible significance of genetic variations. The study also addresses methodological problems related to the quantitation of salivary antibodies by solid-phase immunoassays.     

Degradation of human secretory immunoglobulin A by Blastocystis

Microbial immunoglobulin A (IgA) proteases cleave human secretory IgA, promoting the mucosal adhesion of pathogens. To investigate if the enteric protozoan Blastocystis degrades human secretory IgA, cell lysate and conditioned medium from two species were exposed to immunoglobulin A. Secretory IgA was cleaved by both cell lysate and conditioned medium with mainly cysteine proteinase activity in B. hominis B isolate and aspartic proteinase activity in B. ratii WR1 isolate. These findings suggest that Blastocystis proteases may play a role in parasite survival in vivo.     

Human secretory immunoglobulin A may contribute to biofilm formation in the gut

It is critical, both for the host and for the long-term benefit of the bacteria that colonize the gut, that bacterial overgrowth with subsequent bacterial translocation, which may lead to sepsis and death of the host, be avoided. Secretory IgA (sIgA) is known to be a key factor in this process, agglutinating bacteria and preventing their translocation in a process termed 'immune exclusion'. To determine whether human sIgA might facilitate the growth of normal enteric bacteria under some conditions, the growth of human enteric bacteria on cultured, fixed human epithelial cells was evaluated in the presence of sIgA or various other proteins. Human sIgA was found to facilitate biofilm formation by normal human gut flora and by Escherichia coli on cultured human epithelial cell surfaces under conditions in which non-adherent bacteria were repeatedly washed away. In addition, the presence of sIgA resulted in a 64% increase in adherence of E. coli to live cultured epithelial cells over a 45-min period. Mucin, another defence factor thought to play a key role in immune exclusion, was found to facilitate biofilm formation by E. coli. Our findings suggest that sIgA may contribute to biofilm formation in the gut.     

Secretory immunoglobulin A and cardiovascular reactions to mental arithmetic and cold pressor

Secretory immunoglobulin A (sIgA) in saliva and cardiovascular reactions to mental arithmetic and cold pressor tasks were recorded in 16 healthy young men on two sessions, 4 weeks apart. Both tasks elicited significant increases in sIgA secretion rate, reflecting increases in both salivary volume and sIgA concentration. Whereas mental arithmetic elicited a mixed pattern of alpha- and beta-adrenergic cardiovascular reactions, the pattern of reactions to cold pressor was predominantly alpha-adrenergic. Task levels of sIgA secretion rate, sIgA concentration, and saliva volume showed moderate to high test–retest reliability ( r = .52–.83), although test-retest correlations were less impressive for change scores ( r =−.19–.53). The pattern of correlations between change in sIgA secretion rate and cardiovascular reactivity variables was inconsistent.     

Intestinal secretory immunoglobulin A response to enteroaggregative Escherichia coli in travelers with diarrhea

We examined stool samples from travelers for secretory immunoglobulin A (sIgA) to enteroaggregative Escherichia coli (EAEC) during episodes of acute diarrhea. Ten paired samples from 10 patients with diarrhea caused by EAEC were examined for the presence of specific sIgA by dot blot and Western blot immunoassays. Five samples were positive by dot blotting, and two samples were positive by Western blotting.     

Modulation of secretory immunoglobulin A in saliva; response to manipulation of mood

Secretory immunoglobulin A (sIgA) measured in saliva, an index of mucosal immunity, has repeatedly been shown to be sensitive to psychological variables. Chronic stress is downregulatory whereas an acute psychological challenge induces mobilisation. We examined whether an acute manipulation of mood to induce negative hedonic tone would be downregulatory, as in the chronic stress paradigm and further, whether induction of positive mood might have opposite effects. Two separate experiments were conducted. In the first, mood manipulation was by mental recall and in the second by music. For both sIgA concentration and sIgA secretion rate there was a significant elevation in response to the mood manipulation by recall regardless of hedonic tone. There was some evidence that for sIgA secretion rate the response was more pronounced for positive mood. Mood induction by music also resulted in significant elevations in sIgA concentration and secretion rate and responses were not distinguished by mood valence. None of the mood induction procedures was associated with changes in free cortisol. In these studies, we found no evidence that transient lowering of mood was downregulatory for salivary sIgA. The predominant finding was of sIgA mobilisation.     

Interference of secretory immunoglobulin A with sorption of oral bacteria to hydroxyapatite.

The potential of secretory immunoglobulin A (S-IgA) to interfere with the initial phase of dental plaque formation was studied by using an in vitro method which permits the quantitative determination of the sorption of radiolabeled oral bacterial cells to hydroxyapatite (HA) beads. The importance of specific S-IgA antibodies was evaluated by a comparison of the effect of pure preparations of colostral S-IgA, polymeric myeloma IgA, or preabsorbed S-IgA. Specific antibody molecules bound at the HA surface significantly enhanced the sorption of two Streptococcus sanguis strains. In contrast, HA-bound S-IgA antibodies inhibited the sorption of Streptococcus mitior and Streptococcus salivarius. The same was true for Streptococcus mutans cells, but only when they were propagated in the absence of sucrose. Suspended in saliva, cells of all streptococcal species adhered in significantly lower numbers to HA. Comparative experiments with bacteria suspended in solutions of various preparations of IgA or immunoglobulin-deficient salivas with S-IgA or myeloma IgA added indicated that the adherence inhibition seen with S. Sanguis, S. mitior, S. salivarius, and glucose-grown S. mutans was partly attributable to functions of S-IgA antibodies. Under the in vitro conditions of the study, S-IgA antibodies had no effect on the sorption of sucrose-grown S. mutans, Actinomyces viscosus, and Actinomyces naeslundii to HA. The results indicated that S-IgA can interfere with the sorption of some oral bacteria to HA by several different functions.     

Different secretory immunoglobulin A antibody responses to cholera vaccination in Swedish and Pakistani women.

The capacity of subcutaneous cholera vaccination to induce an antibody response in milk and saliva was studied in lactating Swedish and Pakistani women, since secretory immunoglobulin A (SIgA) antibody responses in these secretions may reflect intestinal immunity. Before immunization, most of the Pakistani women had significant titers of specific SIgA antibodies against Vibrio cholerae lipopolysaccharide in milk, whereas only a few of the Swedish women had measurable, low titers. In the Pakistani women a single subcutaneous injection of cholera vaccine gave rise to a significant SIgA titer rise in 70% of the milk and 45% of the saliva samples. The Swedish women, on the other hand, did not respond with a significant antibody response of any immunoglobulin class in milk or saliva, either after a single or after a booster dose 14 days later. In serum, however, the vaccination induced significant titer rises, mainly of IgG antibodies, also in the Swedish women, but these rises were of lower magnitude than those in the Pakistani group. The results suggest a significant difference in the capacity of parenterally administered cholera vaccine to stimulate SIgA antibody formation in naturally primed and nonprimed individuals.     

Naturally occurring secretory immunoglobulin A antibodies to Streptococcus mutans in human colostrum and saliva.

Human colostrum, parotid saliva, and serum were assayed for the presence of naturally occurring antibodies to five serotypes of Streptococcus mutans. Appreciable levels of agglutinins to strains AHT, BHT, 10449, 6715, and LM-7 (groups a leads to e, respectively) were detected in normal colostrum and saliva, whereas relatively low levels were found in serum. No agglutinins could be detected in the colostrum or saliva of immunodeficient patients. Molecular sieve chromatography of the colostrum on Sephadex G-200 revealed agglutinin activity in the secretory immunoglobulin A (s-IgA)-rich fraction only. Titration of purified colostral s-IgA confirmed the IgA nature of this agglutinating activity. Indirect immunofluorescence tests with anti-s-IgA, -IgG, and -IgM revealed S. mutans specificity only in the s-IgA class. The presence of s-IgA antibodies to indigenous oral microorganisms in colostrum, as well as in saliva, suggests that antigenic stimulation occurs at a site remote from the oral mucosa.     

Serum and salivary immunoglobulin A and free secretory component in ulcerative colitis

Patients with ulcerative colitis have been investigated for evidence of defects in secretory immunity. Total serum IgA concentration, serum IgA antibody titres to Candida albicans, salivary IgA and free secretory component concentrations have been measured in thirty-six patients with ulcerative colitis and thirty-six normal controls. None of the parameters was significantly different between patients with proctitis and patients with extensive colitis or between the colitis patients and normal controls.     

Slow subcutaneous immunoglobulin therapy in a patient with reactions to intramuscular immunoglobulin

A 35-year-old man with common variable hypogammaglobulinemia had repeated anaphylactic reactions to intramuscular human immune serum globulin (HISG), preventing him from receiving the injections. He was able to tolerate slow subcutaneous HISG infusions without local or systemic side effects at a dose of 12 ml/week given at a rate of 2 ml/hr. He has been maintained on these infusions for 2 years in an infection-free state.     

Secretory immunoglobulin A and cardiovascular reactions to mental arithmetic, cold pressor, and exercise: effects of alpha-adrenergic blockade

The mechanism underlying acute changes in secretory immunoglobulin A (sIgA) remains to be determined. In this experiment, sIgA and cardiovascular activity were monitored at rest and while participants performed a mental arithmetic task, cold pressor, and submaximal cycle exercise following placebo or 1 mg of the alpha-adrenergic blocker, doxazosin. Under placebo, the tasks produced patterns of cardiovascular activity indicative of combined alpha- and beta-adrenergic, alpha-adrenergic, and beta-adrenergic activation, respectively. Doxazosin was associated with reduced blood pressure during cold pressor, but not during arithmetic or exercise. Mental arithmetic elicited increases in sIgA concentration and exercise produced increases in both sIgA concentration and secretion rate; these changes were unaffected by alpha blockade. In contrast, the cold pressor was associated with decreases in both sIgA concentration and secretion rate, which were blocked by doxazosin. These data suggest that acute decreases, but not increases, in sIgA are mediated by alpha-adrenergic mechanisms.     

Immunoglobulin A and secretory immunoglobulin A antibodies to purified type 1 Klebsiella pneumoniae pili in human colostrum.

Immunoglobulin A antibodies with binding specificity for purified Klebsiella pneumoniae type 1 pili were detected by an enzyme-linked immunosorbent assay in 20 of 21 human samples (95%). The concentrations of secretory immunoglobulin A antibody in colostrum directed against the pili were calculated by comparison of experimental enzyme-linked immunosorbent assay values with values obtained from known secretory immunoglobulin A concentrations. The presence of antibodies to K. pneumoniae type 1 pili was confirmed by double diffusion-gel studies with selected specimens of colostrum. This study shows that in the majority of human colostral samples examined, secretory immunoglobulin A antibodies with specificity for K. pneumoniae type 1 pili can be commonly found in variable, but frequently high, concentrations.     

Natural polyreactive secretory immunoglobulin A autoantibodies as a possible barrier to infection in humans.

Secretory immunoglobulin A (S-IgA) was investigated in human secretions for the presence of natural antibodies (Abs) acting as the first "immune barrier" to infection before induction or boosting of specific responses. These molecules could be the secretory counterpart of the natural Abs in serum that were previously shown by our laboratory to be polyreactive to autoantigens. Significant levels of S-IgA Abs to human actin, myosin, tubulin, and spectrin were detected in 10 saliva and 8 colostrum samples from normal subjects. Computer-assisted analysis of immunoblots of extracts from human muscles showed these Abs to react with a large number of autoantigens. Their polyreactivity was confirmed by cross-inhibition and by immunoblotting studies of affinity-purified natural Abs, assayed against a large variety of surface or secreted antigens from Streptococcus pyogenes. The thiocyanate elution method showed that functional affinities of some natural Abs can be of the same order of magnitude as those of tetanus vaccine antitoxins. Moreover, nonimmune binding of these natural Abs to the gut protein Fv (Fv-fragment binding protein) can enhance their effector functions. This demonstrates that human secretions contain polyreactive auto-Abs which can also react with pathogens. These secretory Abs of "skeleton key" specificities are possibly produced by a primordial B-1-cell-associated immune system and can be involved in a plurispecific mucosal protection against pathogens, irrespective of the conventional immune response.     

Human secretory immunoglobulin A anti-Entamoeba histolytica antibodies inhibit adherence of amebae to MDCK cells.

The presence of secretory immunoglobulin A (IgA) anti-Entamoeba histolytica antibodies in the saliva of patients with intestinal amebiasis was demonstrated by immunoblot assay, and the capacity of these antibodies to inhibit amebic adherence to a monolayer of MDCK cells was analyzed. Inhibition was due to IgA antiamebic antibodies and in part to anti-Gal-binding-lectin antibodies, as demonstrated by absorption experiments with total amebic extract and with the fraction of Gal-binding lectin. These results emphasize the relevance of secretory IgA antibodies in the phenomenon of E. histolytica adherence to epithelial cells.