Detection of antisynthetic mannoside antibodies (ASigmaMA) reveals heterogeneity in the ASCA response of Crohn's disease patients and contributes to differential diagnosis, stratification, and prediction.
OBJECTIVE
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 (SigmaMan3) and Man alpha-1,3 Man alpha-1,2 Man alpha-1,2 Man (SigmaMan4), and then explored how antisynthetic mannoside antibodies (ASigmaMA) 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 ASigmaMA and ASCA included a total of 1,365 subjects: 772 CD, 261 UC, 43 IC, and 289 controls.


RESULTS
The specificity of ASigmaMA 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 ASigmaMA. ASigmaMA 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
ASigmaMA 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 ASigmaMA had preferentially a colonic involvement, which confirms the high predictive value of ASigmaMA for determining IC evolution toward CD.
Vandewalle-El Khoury
Peggy
P
Inserm, U799, Lille, France.
Colombel
Jean-Frederic
JF
Joossens
Sofie
S
Standaert-Vitse
Annie
A
Collot
Mayeul
M
Halfvarson
Jonas
J
Ayadi
Ali
A
Landers
Carol J
CJ
Vermeire
Severine
S
Rutgeerts
Paul
P
Targan
Stephan R
SR
Chamaillard
Mathias
M
Mallet
Jean-Maurice
JM
Sendid
Boualem
B
Poulain
Daniel
D
D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D000908:Antibodies, Fungal / Q000097:blood; D016022:Case-Control Studies; D003424:Crohn Disease / Q000175:diagnosis* / Q000276:immunology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008351:Mannans / Q000276:immunology*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D019268:Antibodies, Antineutrophil Cytoplasmic; D000908:Antibodies, Fungal; D008351:Mannans