ASCA, ANCA, ALCA and Many More: Are They Useful in the Diagnosis of Inflammatory Bowel Disease?

Abstract

Background: Inflammatory bowel disease (IBD) is characterized by excessive immune responses to altered intestinal microbiota in genetically susceptible individuals. The diagnosis of IBD depends on clinical, endoscopic, histological, radiological and biochemical criteria, which may be invasive, time consuming and usually not accepted by patients with IBD. Key Messages: Serological biomarkers have been demonstrated to be a series of rapid, non-invasive approaches for assessments of early diagnosis, disease activity and prognosis for IBD. Importantly, serum antibodies against microbial antigens or auto-antigens have been used as biomarkers in predicting disease course, complications and responses to medications and surgery. Moreover, they have been demonstrated to be useful in distinguishing patients with Crohn's disease (CD) from those with ulcerative colitis (UC). Recently, a great number of new serum biomarkers (e.g., anti-glycoprotein 2, anti-granulocyte macrophage colony-stimulating factor, anti-neutrophil cytoplasmic antibody, anti-Saccharomyces cerevisiae antibody, anti-laminaribioside carbohydrate IgG antibody, anti-mannobioside carbohydrate IgG antibody, antibody to the outer membrane protein of Escherichia coli, anti-CBir1) have been found to be present in patients with IBD and are potentially used in the diagnosis and prediction. The presence of these antibodies in the sera is due to the disruption of intestinal mucosa barrier and they may reflect a possibly genetic loss of immunological tolerance toward microbiota-derived antigens. Due to their non-invasive, easily accessible, repetitive and economical characteristics, these biomarkers have been found to serve as precious supplementary means in the diagnosis and disease evaluation of IBD. Conclusions: Currently, the most important utility of serological biomarkers is to evaluate the aggressive risks of disease phenotype, complications or surgery requirement, predict prognosis of the disease and distinguish CD from UC. However, they have limited values in making initially definite diagnosis for IBD. Therefore, more effective biomarkers with high sensitivity and specificity need to be further explored in the future.

Neutrophils in ulcerative colitis: a review of selected biomarkers and their potential therapeutic implications

“…Cat-G expression has been found to be higher in colonic biopsies and fecal supernatants from patients with UC compared to healthy subjects (102). Interestingly, it has been shown that not only is PAR4 expression higher in these biopsies, but it is also located mainly in crypts and is internalized following activation on epithelial cells.…”

The Dual Role of Neutrophils in Inflammatory Bowel Diseases

“…This suggests that these patients possess a serum microenvironment that is able to induce neutrophil-derived NETs. This could be due to anti-neutrophil cytoplasmic antibodies (ANCAs) found in serum of patients [150]. ANCAs can indeed be directed against NET components, such as MPO, NE, cathespin G or proteinase 3.…”

Review article: the role of the autonomic nervous system in the pathogenesis and therapy of IBD

“…These results are of significant interest given that the last decade has seen a number of studies supporting the theory of intestinal barrier perturbation in the pathogenesis of IBD . Additionally, the detection of circulating antibodies directed against microbial antigens (such as “ASCA”—epitopes of Saccharomyces cerevisiae ‐ and flagellin CBir1) prior to the development of IBD suggest that a disruption of the intestinal barrier function may be present prior to the clinically evident onset of disease. Furthermore, a genetic predisposition to intestinal barrier perturbation is considered to be a predisposing factor in the development of IBD .…”