Antibodies Against Laminaribioside and Chitobioside Are Novel Serologic Markers in Crohn’s Disease

Background & Aims: New serologic markers of inflammatory bowel disease may be useful for differentiating between Crohn’s disease and ulcerative colitis and for disease stratification. We profiled sugar-binding antibodies to identify novel antiglycan antibodies that may be associated with inflammatory bowel disease. Methods: Serum samples were obtained from patients with diagnosed Crohn’s disease or ulcerative colitis and from control patients. The presence of antiglycan antibodies was evaluated using either a glycan array (GlycoChip; Glycominds, Ltd, Lod, Israel) in patients with Crohn’s disease (n = 72) or ulcerative colitis (n = 56) and in healthy controls (n = 41) or using an enzyme-linked immunosorbent assay in patients with Crohn’s disease (n = 124), ulcerative colitis (n = 106), and in control patients (n = 101). Results: Inaddition to antibodies against mannan, antibodies to laminaribioside (Glc[β1,3]Glc[β]) and chitobioside (GlcNAc[β1,4]GlcNAc[β]) had the highest discriminative capability between Crohn’s disease and ulcerative colitis (P < .001 and P < .05, respectively). Importantly, 44% (12/27) of anti-Saccharomyces cerevisiae antibody-negative Crohn’s disease patients were positive for antilaminaribioside or antichitobioside. In patients with inflammatory bowel disease positive for antibodies against either laminaribioside, chitobioside, or mannan, the diagnosis of Crohn’s disease was suggested with a sensitivity of 77.4% and specificity of 90.6%. Having at least 2 of these antibodies increased the specificity to 99.1%. In Crohn’s disease, higher levels of antibodies against laminaribioside or mannan were significantly associated with small intestinal disease (P = .03 and P < .0001, respectively). Conclusions: Antilaminaribioside and antichitobioside carbohydrate antibodies are novel serologic markers associated with Crohn’s disease. These antibodies may contribute to the diagnosis and improved stratification of Crohn’s disease.

Abbreviations used in this paper:  ACCA, antichitobioside carbohydrate IgA antibodies , ALCA, antilaminaribioside carbohydrate IgG antibodies , ASCA, anti-Saccharomyces cerevisiae antibodies , AUC, area under the curve , CD, Crohn’s disease , gASCA, anticovalently attached mannan antibodies , HC, healthy controls , OGD, other-than-IBD gastrointestinal diseases , RFU, relative fluorescence units , UC, ulcerative colitis