Gastroenterology

Gastroenterology

Volume 130, Issue 6, May 2006, Pages 1764-1775
Gastroenterology

Basic–alimentary tract
Candida albicans Is an Immunogen for Anti–Saccharomyces cerevisiae Antibody Markers of Crohn’s Disease

https://doi.org/10.1053/j.gastro.2006.02.009Get rights and content

Background and Aims: Antibodies directed against oligomannose sequences α-1,3 Man (α-1,2 Man α-1,2 Man)n (n = 1 or 2), termed anti–Saccharomyces cerevisiae antibodies (ASCAs) are markers of Crohn’s disease (CD). 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 (Σ) 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.

Section snippets

Patients

Twenty-seven patients with CD (16 females, 11 males; 26–88 years of age), 17 patients with proven systemic candidiasis (7 females, 10 males; 1–79 years of age), 25 patients with UC (12 females, 13 males; 27–76 years of age), and 10 healthy controls (5 females, 5 males; 19–40 years of age) were included in the study. Sera from all subjects were collected from the Clinical Mycology Laboratory of the University Hospital of Lille. Diagnosis of CD or UC was based on clinical, endoscopic, and

Bioclinical Evidence for a Relationship Between Generation of ASCA and Anti–C albicans Antibodies in Patients With CD and Candidiasis

Although ASCAs are usually stable serologic markers of CD, it was possible to select 3 patients from our diagnostic serum bank who presented ASCA seroconversion (from negative to positive) during their serologic monitoring. The clinical characteristics of these patients are summarized in Table 2. Sequential analysis of ASCA titers in these 3 CD patients is shown in Figure 1A. During the follow-up period of between 400 and 1000 days, ASCA titers against S cerevisiae PPM became significant for CD

Discussion

The main result of this study is that C albicans was found to express the major ASCA epitopes on several cell wall molecules. Overexpression of ASCA epitopes by C albicans was shown to be triggered by growth conditions. Among these, the pathogenic phase of C albicans was shown to be a strong immunogen for ASCA.

Initial clinical studies performed by using different yeast species and strains revealed the presence of antibodies to both C albicans and S cerevisiae in sera from patients with

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    Supported by the François Aupetit Association and the European Community-FEDER Fund, program Interreg III-A.

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