The Utility of serological markers in inflammatory bowel diseases: Gadget or magic?

The panel of serologic markers for inflammatory bowel diseases (IBD) is rapidly expanding. Anti–Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) remain the most widely investigated; however there are methodological difficulties and no clear guidelines for immunofluorescence detection and interpretation of ANCA patterns in IBD hampering the diagnostic potential of the test. Increasing amount of experimental data is available on newly discovered antibodies directed against various microbial proteins and carbohydrates. Such antibodies include anti-OmpC (outer membrane porin C), anti- Pseudomonas fluorescens (anti-I2), anti-flagellin antibody CBir1 and antiglycan antibodies (anti-laminaribioside carbohydrate antibody [ALCA], anti-chitobioside carbohydrate antibody [ACCA], anti-mannobioside carbohydrate antibody [AMCA]). The pathogenic significance of these antibodies has not been established and it remains unclear whether they arise as a result of tissue damage, increased permeability or the mucosal immune perturbation seen in Crohn’s disease. Reactivity to microbial components was associated with NOD2/CARD15 genotype. Moreover, positive correlation was found between the number of mutations and the prevalence of antimicrobial antibodies (gene dosage effect), further supporting the role of altered microbial sensing in the pathogenesis of Crohn’s disease. The role of the assessment of various antibodies in the current IBD diagnostic algorithm is often questionable due to their limited sensitivity. In contrast, the association of serologic markers with disease behaviour and phenotype is becoming increasingly well-established. An increasing number of observations confirm that patients with Crohn’s disease expressing multiple serologic markers at high titers are more likely to have complicated small bowel disease (e.g. stricture and/or perforation) and are at higher risk for surgery than those without, or with low titer of antibodies (serology dosage effect). Creating homogenous disease sub-groups based on serologic response may help develop more standardized therapeutic approaches and may help in a better understanding of the pathomechanism of inflammatory bowel diseases. Further prospective clinical studies are needed to establish the clinical role of serologic tests in IBD