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THE UTILITY OF TWO NOVEL POLYSACCHARIDE ANTIBODIES (ANTI-LAMINARIN AND ANTI-CHITIN) IN DIAGNOSING CROHN’S DISEASE AND THEIR ASSOCIATION WITH AGGRESSIVE DISEASE
CH Seow1,2, JM Stempak1, W Xu3, H Lan3, AM Griffiths4, GR Greenberg1, AH Steinhart1, N Dotan5, MS Silverberg1
1Mount Sinai Hospital, Toronto; 2University of Western Australia, Australia; 3Biostatistics, University of Toronto; 4Hospital for Sick Children, Toronto; 5Glycominds Ltd, Israel
BACKGROUND AND AIM: A panel of polysaccharide antibodies directed against infectious pathogens has been proposed as useful in differentiating Crohn’s disease (CD) from ulcerative colitis (UC) and for predicting disease behaviour. These include Anti Saccharomyces cerevisiae Antibodies (gASCA), Anti Laminaribioside Carbohydrate Antibodies (ALCA), Anti Chitobioside Carbohydrate Antibodies (ACCA) and Anti Mannobioside Carbohydrate Antibodies (AMCA). Our aim was to determine if two novel IgA cell wall polysaccharide antibodies anti-L (anti-Laminarin) and anti-C (anti-Chitin) contribute to diagnosis and phenotype differentiation.
METHODS: A cohort of 851 paediatric and adult IBD patients (517 CD, 301 UC, 33 IC) and 97 healthy controls were analysed for gASCA IgG, gASCA IgA, ACCA, ALCA, AMCA, anti-L and anti-C.
RESULTS: gASCA IgG, gASCA IgA, ACCA, ALCA, AMCA, anti-L and anti-C were significantly more prevalent in patients with CD versus patients with UC (p<0.0015). On ROC curve analysis, gASCA IgG and IgA were the most useful markers in differentiating CD from UC, followed by anti-L. Anti-L and Anti-C were highly specific for CD (96.7% and 97.7% respectively). The addition of anti-L to the existing five markers (gASCA IgG, gASCA IgA, ACCA, ALCA, AMCA) significantly improved differentiation between CD and UC (p=0.01); the addition of anti-C was not as useful (p=0.03). With respect to CD, an increasing number of positive antibodies was associated with earlier disease onset, longer disease duration (both p<0.005) and more aggressive disease behaviour; i.e. penetrating phenotype, perianal disease and the need for abdominal surgery (all p<0.0005). Using multivariate logistic regression, anti-L was independently associated with the need for abdominal surgery (OR 1.76, 95% CI 1.08-2.87; p=0.02), while anti-C was strongly associated with a penetrating phenotype (OR 2.76, 95% CI 1.51-5.06; p=0.001) and with perianal disease (OR 2.17, 95% CI 1.19-3.95; p=0.0112).
CONCLUSIONS: The addition of anti-L and anti-C to a serological panel further aids in the differentiation between CD and UC. These novel markers also independently predict aggressive disease behaviour.
Partial funding received from Glycominds Ltd.