Antibodies to Saccharomyces cerevisiae in patients with Crohn's disease and their possible pathogenic importance.

Abstract

Initial attachment of the cariogenic Streptococcus mutans onto dental enamel is largely promoted by the adsorption of specific salivary proteins on enamel surface. Some phosphorylated salivary proteins were found to reduce S. mutans adhesion by competitively inhibiting the adsorption of S. mutans-binding salivary glycoproteins to hydroxyapatite (HA). The aim of this study was to develop antiadherence compounds for preventing dental biofilm development. We synthesized phosphorylated polyethylene glycol (PEG) derivatives and examined the possibility of surface pretreatment with them for preventing S. mutans adhesion in vitro and dental biofilm formation in vivo. Pretreatment of the HA surface with methacryloyloxydecyl phosphate (MDP)-PEG prior to saliva incubation hydrophilized the surface and thereby reduced salivary protein adsorption and saliva-promoted bacterial attachment to HA. However, when MDP-PEG was added to the saliva-pretreated HA (S-HA) surface, its inhibitory effect on bacterial binding was completely diminished. S. mutans adhesion onto S-HA was successfully reduced by treatment of the surface with pyrophosphate (PP), which desorbs salivary components from S-HA. Treatment of S-HA surfaces with MDP-PEG plus PP completely inhibited salivapromoted S. mutans adhesion even when followed by additional saliva treatment. Finally, mouthwash with MDP-PEG plus PP prevented de novo biofilm development after thorough teeth cleaning in humans compared to either water or PP alone. We conclude that MDP-PEG plus PP has the potential for use as an antiadherence agent that prevents dental biofilm development.Dental plaque, a complex microbial biofilm, is the primary etiologic factor in dental caries. Colonization of enamel surfaces by the cariogenic bacterium Streptococcus mutans is thought to be initiated by attachment to a saliva-derived conditioning film, the acquired enamel pellicle (9). The acquired enamel pellicle is formed largely by adsorption of heterogeneous salivary proteins (1, 18) onto dental enamel (ϳ98% [wt/wt] hydroxyapatite [HA]) and promotes the adhesion of S. mutans by specific (2, 17) and nonspecific (4) mechanisms.Saliva contains a multitude of proteins that contribute to oral microbial ecology and biofilm formation (6,16,32). A variety of salivary proteins have been shown to modulate bacterial adhesion onto HA surfaces in vitro. Adsorption of specific salivary proteins, such as acidic proline-rich proteins (8) and agglutinin (3), promotes the adhesion of S. mutans onto HA surfaces by providing ligands for bacterial attachment. Many studies thus far have suggested that an initial bacterial adhesion promoted by salivary protein adsorption onto the enamel surface contributes to facilitate dental biofilm development.Recently, we reported the clinical relevance of saliva-promoted S. mutans adhesion in both de novo dental biofilm development and caries experience (29). Dental biofilm formation after thorough teeth cleaning was positively correlated with both salivary glycoprotein content and S. mutans a...

Inflammatory bowel disease: autoimmune or immune-mediated pathogenesis?

“…Levels of serum antibodies against multiple strains of S. cerevisiae (baker's and brewer's yeast) were found to be significantly elevated in the serum of CD patients, but not serum of UC patients (McKenzie et al, 1990;Giaffer et al, 1992). This was initially proposed as potentially indicating hypersensitivity to dietary antigens in CD.…”

“…A number of reports show that CD and UC patients have increased titers of antibodies against E. coli, aerobes, anaerobes and even enteric bacterial pathogens, and that these antibodies are of both systemic and mucosal origin (Monteiro et al, 1971;Tabaqchali et al, 1978;Blaser et al, 1984;Macpherson et al, 1996). The previously discussed ASCA in CD patients probably reflect the same type of broad anti-microbial reactivity associated with IBD (McKenzie et al, 1990;Giaffer et al, 1992). More recently, novel gut bacterial antigens have been reported in association with IBD, including the Pseudomonas fluorescens-associated sequence I2, the outer membrane porin C of E. coli (OmpC), and bacterial flagellins, towards which CD patients develop significantly higher antibody titers than UC or control subjects (Sutton et al, 2000;Landers et al, 2002;Lodes et al, 2004).…”

“…This hypothesis has not been pursued to any significant extent and is still a theoretical possibility, but it is well established that ASCA recognize mannose sequences in the cell wall mannan of S. cerevisiae, defining ASCA as a non autoantigen in IBD. Although not totally specific for CD, as ASCA can be detected in serum of some celiac disease patients (Giaffer et al, 1992), the lack of antibodies in the circulation of UC patients suggested that the combined measurement of pANCA and ASCA could help in the differential diagnosis of the two forms of IBD, a typically challenging situation for the practicing gastroenterologist. Two studies, one performed with adult and the other with pediatric subjects in which sera from UC and CD patients were assessed for both pANCA and ASCA, showed that the combination of a positive pANCA and a negative ASCA was highly specific (95 -100%) for UC, whereas the combination of a negative pANCA and a positive ASCA was highly specific (95 -100%) for CD (Ruemelle et al, 1998;Quinton et al, 1998).…”

Anti-Saccharomyces cerevisiaeantibody titers are stable over time in Crohn’s patients and are not inducible in murine models of colitis

“…Additionally, both brewing and baking strains of S cerevisiae provoke an antibody response in CD, implicating dietary antigens in disease pathogenesis [4] . One group has noted higher ASCA IgG antibody levels in patients with small bowel Crohn's disease vs those with colonic disease [18] . This same study found high levels of ASCA IgG but not IgA in celiac disease, indistinguishable from levels seen in CD.…”

“…Nevertheless, some of the familial studies have yielded conflicting data. For example, one group showed increased ASCA production in familial vs sporadic CD [7] , but others have shown equal or increased ASCA prevalence for sporadic CD [9,[16][17][18] . Thus, the case for an environmental etiology for ASCA has been articulated as well.…”