Partial overlap of anti-mycobacterial, and anti-Saccharomyces cerevisiae mannan antibodies in Crohn's disease.
OBJECTIVE
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).


CONCLUSIONS
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.
Müller
Stefan
S
Department of Clinical Research, Division of Gastroenterology, University of Bern, Bern CH-3010, Switzerland.
Schaffer
Thomas
T
Schoepfer
Alain M
AM
Hilty
Annamarie
A
Bodmer
Thomas
T
Seibold
Frank
F
D000328:Adult; D000368:Aged; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000908:Antibodies, Fungal / Q000097:blood*; D000917:Antibody Formation; D000918:Antibody Specificity; D016022:Case-Control Studies; D003424:Crohn Disease / Q000276:immunology* / Q000382:microbiology; D003429:Cross Reactions; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008351:Mannans / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009161:Mycobacterium / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology
D000907:Antibodies, Bacterial; D000908:Antibodies, Fungal; D007074:Immunoglobulin G; D008351:Mannans