Novel anti-glycan antibodies related to inflammatory bowel disease diagnosis and phenotype.
OBJECTIVE
We sought to evaluate whether two novel immunoglobulin A (IgA) cell wall polysaccharide antibodies, anti-laminarin (anti-L) and anti-chitin (anti-C), aid in the diagnosis and phenotype differentiation of Crohn's disease (CD) and ulcerative colitis (UC).


METHODS
A cohort of 818 individuals with inflammatory bowel disease (IBD; 517 CD and 301 UC) from two IBD tertiary referral centers, with median ages of 33 and 39 years, respectively, and disease duration of 8.9 years, were phenotyped using the Montreal classification, and analyzed for seven anti-glycan antibodies (gASCA (anti-Saccharomyces cerevisiae) IgG, gASCA IgA, anti-chitobioside (GlcNAc(beta1,4)GlcNAc(beta)), anti-laminaribioside (Glc(beta1,3)Glb(beta)), anti-mannobioside (Man(alpha1,3)Man(alpha)), anti-L, and anti-C) and perinuclear atypical neutrophil cytoplasmic antibodies (pANCA).


RESULTS
In the CD patient population, 73% were positive for >/=1 anti-glycan antibody. All glycan markers were specific for CD (85.4-97.7%) and more prevalent in CD vs. UC (P<0.0015). gASCA IgG and IgA best differentiated CD from UC followed by anti-L (area under the curve 0.818, 0.815, and 0.702, respectively). The addition of anti-L and anti-C to gASCA IgG and pANCA improved discrimination between CD and UC (P<0.001). Adding anti-L to gASCA and pANCA differentiated colonic CD and UC (P=0.02). An increasing number of positive antibodies was associated with early CD onset, penetrating phenotype, perianal disease, and the need for surgery (P<0.001). Anti-L was associated with ileocolonic CD (odds ratio (OR) 2.28, 95% confidence interval (CI) 1.40-3.69; P=0.001), and anti-C with penetrating (OR 2.75, 95% CI 1.50-5.04; P=0.001) and perianal disease (OR 1.95, 95% CI 1.06-3.59; P=0.03).


CONCLUSIONS
Anti-L and anti-C improve differentiation between CD and UC. Anti-L may also differentiate between isolated colonic CD and UC. Both anti-L and anti-C are independently associated with a more aggressive CD phenotype.
Seow
Cynthia H
CH
Division of Gastroenterology, Mount Sinai Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Stempak
Joanne M
JM
Xu
Wei
W
Lan
Hui
H
Griffiths
Anne M
AM
Greenberg
Gordon R
GR
Steinhart
A Hillary
AH
Dotan
Nir
N
Silverberg
Mark S
MS
D000293:Adolescent; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood* / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011134:Polysaccharides / Q000276:immunology*; D012372:ROC Curve; D055815:Young Adult
D019268:Antibodies, Antineutrophil Cytoplasmic; D007070:Immunoglobulin A; D011134:Polysaccharides