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. 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 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 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 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 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. .