Candida albicans is an immunogen for anti-Saccharomyces cerevisiae antibody markers of Crohn's disease

Background and Aims: Antibodies directed against oligomannose sequences alpha-1,3 Man (alpha-1,2 Man alpha-1,2 Man)(n) (n = 1 or 2), termed anti-Saccharomyces cerevisiae antibodies (ASCAs) are markers of Crohn's disease (CID). S cerevisiae mannan, which expresses these haptens, is used to detect ASCA, but the exact immunogen for ASCA is unknown. Structural and genetic studies have shown that Candida albicans produces mannosyltransferase enzymes that can synthesize S cerevisiae oligomannose sequences depending on growth conditions. This study investigated whether C albicans could act as an immunogen for ASCA. Methods: Sequential sera were collected from patients with CD, systemic candidiasis, and rabbits infected with C albicans. Antibodies were purified by using chemically synthesized (1) ASCA major epitopes. These affinity-purified antibodies and lectins were then used to analyze the expression of ASCA epitopes on molecular extracts and cell walls of C albicans and S cerevisiae grown in various conditions. Results: In humans and rabbits, generation of ASCA was shown to be associated with the generation of anti-C albicans antibodies resulting specifically from infection. By using affinity-purified antibodies, C albicans was shown to express ASCA epitopes on mannoproteins similar to those of S cerevisiae. By changing the growth conditions, C albicans mannan was also able to mimic S cerevisiae mannan in its ability to detect ASCA associated with CD. This overexpression of ASCA epitopes was achieved when C albicans grew in human tissues, Conclusions: C albicans is one of several immunogens for ASCA and may be at the origin of an aberrant immune response in CD.