ABSTRACT: OBJECTIVES: Anti-S. cerevisiae mannan antibodies (ASCA) are human antibodies associated with Crohn's disease (CD) reacting with Saccharomyces cerevisiae (S. cerevisiae) mannan polymer. As mannan is a complex and variable repertoire of oligomannoses acting as epitopes, we chemically synthesized (Sigma) two major oligomannose epitopes, Man alpha-1,3 Man alpha-1,2 Man (Sigma Man3) and Man alpha-1,3 Man alpha-1,2 Man alpha-1,2 Man (Sigma Man4), and then explored how antisynthetic mannoside antibodies (A Sigma MA) compare with ASCA as markers of CD.
METHODS: The study involved different cohorts of CD and ulcerative colitis (UC) patients and healthy controls who had been studied previously in several medical centers in Europe, the United States, and North Africa to determine the clinical value of ASCA in terms of differential diagnosis, evolution of indeterminate colitis (IC), and serotype-phenotype correlations. The comparison of A Sigma MA and ASCA included a total of 1,365 subjects: 772 CD, 261 UC, 43 IC, and 289 controls.
RESULTS: The specificity of A Sigma MA was similar to that of ASCA (89% vs 93%), although the sensitivity was lower (38% vs 55%). Unexpectedly, 24% of the CD patients who were negative for ASCA and/or other CD-associated serologic markers were positive for A Sigma MA. A Sigma MA were associated with colonic involvement in CD (odds ratio [OR] 1.609, 95% confidence interval [CI] 1.033-2.506, P = 0.03) and were 100% predictive of CD in patients with IC.
CONCLUSIONS: A Sigma MA reveal the heterogeneity of the antioligomannose antibody response in CD patients and increase the sensitivity of CD diagnosis when combined with ASCA. The subset of ASCA-negative CD patients diagnosed by A Sigma MA had preferentially a colonic involvement, which confirms the high predictive value of A Sigma MA for determining IC evolution toward CD.
American Journal of Gastroenterology. 01/2008; 103(4):949-957.