Clinical Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jun 21, 2008; 14(23): 3650-3661
Published online Jun 21, 2008. doi: 10.3748/wjg.14.3650
Partial overlap of anti-mycobacterial, and anti-Saccharomyces cerevisiae mannan antibodies in Crohn’s disease
Stefan Müller, Thomas Schaffer, Alain M Schoepfer, Annamarie Hilty, Thomas Bodmer, Frank Seibold
Stefan Müller, Thomas Schaffer, Alain M Schoepfer, Frank Seibold, Department of Clinical Research, Division of Gastroenterology, University of Bern, Bern CH-3010, Switzerland
Stefan Müller, Thomas Schaffer, Annamarie Hilty, Thomas Bodmer, Institute for Infectious Diseases, University of Bern, Bern CH-3010, Switzerland
Author contributions: Müller S and Schaffer T contributed equally to this work; Müller S contributed to the study design, planned experiments, carried through the animal part of the study and ELISAs with affinity purified sera, and wrote the paper; Schaffer T screened patients’ sera by ELISA, performed neutralization experiments and affinity purifications; Schoepfer AM provided clinical data and performed statistic analyses; Hilty A, and Bodmer T prepared and supervised mycobacterial cultures; and Seibold F had the original idea and designed the study.
Correspondence to: Frank Seibold, Department of Gastroenterology, Inselspital Bern, University Hospital, Freiburgstrasse 10, Bern CH-3010, Switzerland. frank.seibold@insel.ch
Telephone: +41-31-6328025
Fax: +41-31-63297 65
Received: February 11, 2008
Revised: April 14, 2008
Accepted: April 21, 2008
Published online: June 21, 2008
Abstract

AIM: To test whether humoral immune reaction against mycobacteria may play a role in anti-Saccharomyces cerevisiae antibodies (ASCA) generation in Crohn's disease (CD) and/or whether it correlates with clinical subtypes.

METHODS: The dominant ASCA epitope was detected by Galanthus nivalis lectin (GNL)-binding assay. ASCA and IgG against mycobacterial lysates [M avium, M smegmatis, M chelonae, M bovis BCG, M avium ssp. paratuberculosis (MAP)] or purified lipoarabinomannans (LAM) were detected by ELISA. ASCA and anti-mycobacterial antibodies were affinity purified to assess cross-reactivities. Anti-mycobacterial IgG were induced by BCG-infection of mice.

RESULTS: GNL bound to different extents to mycobacterial lysates, abundantly to purified mannose-capped (Man) LAM from M tuberculosis, but not to uncapped LAM from M smegmatis. Fifteen to 45% of CD patients but only 0%-6% of controls were seropositive against different mycobacterial antigens. Anti-mycobacterial IgG correlated with ASCA (r = 0.37-0.64; P = 0.003-P < 0.001). ASCA-positivity and deficiency for mannan-binding lectin synergistically associated with anti-mycobacterial IgG. In some patients, anti-mycobacterial antibodies represent cross-reactive ASCA. Vice-versa, the predominant fraction of ASCA did not cross-react with mycobacteria. Finally, fistulizing disease associated with antibodies against M avium, M smegmatis and MAP (P = 0.024, 0.004 and 0.045, respectively).

CONCLUSION: Similar to ASCA, seroreactivity against mycobacteria may define CD patients with complicated disease and a predisposition for immune responses against ubiquitous antigens. While in some patients anti-mycobacterial antibodies strongly cross-react with yeast mannan; these cross-reactive antibodies only represent a minor fraction of total ASCA. Thus, mycobacterial infection unlikely plays a role in ASCA induction.

Keywords: Crohn’s disease, Anti-mycobacterial antibodies, Anti-Saccharomyces cerevisiae antibodies, Cross-reactivity, Mannan, Lipoarabinomannan