New serologic markers for inflammatory bowel disease diagnosis

Abstract

Inflammatory bowel diseases (IBD) are chronic intestinal disorders where, in genetically susceptible hosts, an intestinal microorganism triggers an over-reactive immune response. Antibodies against luminal antigens are specifically associated with Crohn's disease (CD). In addition to the previously described antibodies antineutrophil cytoplasmic (auto)antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), OmpC, I2 and CBir1 Flagellin, new anti-glycan antibodies were recently added to the armamentarium of serologic markers in IBD. Glycans are sugars associated with proteins, abundant on many living cells. The anti-glycan antibodies are directed against laminaribioside, chitobioside, mannobioside and mannan residues and are designated anti-laminaribioside carbohydrate antibodies (ALCA), anti-chitobioside carbohydrate antibodies (ACCA), anti-mannobioside carbohydrate antibodies (AMCA) and gASCA, respectively. Anti-laminarin IgA (Anti-L), and anti-chitin IgA (Anti-C) are new members of this family. Laminarin and chitobioside are capable of stimulating the innate immune system, thus the finding of antibodies against these glycans suggests a connection between the adaptive and innate arms of the immune response in CD patients. The contribution of serologic markers, specifically the anti-glycan antibodies, to IBD diagnosis may be in differentiating IBD from other gastrointestinal diseases, and between CD and ulcerative colitis (UC), in better classifying undetermined colitis and for decision-making prior to proctocolectmy in UC patients. The anti-glycan antibodies are specifically important in ASCA-negative CD patients. Correlation between serologic markers and genetic variations may contribute to reclassifying IBD into new and more homogeneous subclasses. Their significance in diagnosing populations at risk, such as unaffected relatives of IBD patients and CD patients prior to diagnosis, is under current investigation.