Circulating Antibodies against Bacterial Wall Products: Are There Arguments for Early Immunosuppression?

Abstract

The disease course of inflammatory bowel disease (IBD) is highly heterogeneous and unpredictable. The risk of fistulae formation and stricturing complications that lead to surgery during the disease course is substantial. Use of early and aggressive immunosupressive therapies such as immunomodulation could have the potential for altering the natural history of IBD, namely reducing the number of hospitalizations and surgeries. If diagnostic tools are available to predict disease activity, response to therapy, disease complications as well as the need for surgery or hospitalizations, one could identify IBD patients at risk that might benefit from more intense immunosuppression. Circulating antibodies against bacterial wall products, such as anti-Saccharomyces cervisiae antibodies have been investigated for the diagnosis and disease stratification of IBD. These markers are mainly linked to Crohn’s disease (CD), are associated with genetic polymorphisms such as NOD2, and are linked to and possibly predictive of complicated CD behavior and CD-related surgery. No association of these antibodies has been found on assessment of disease activity, tissue healing or surgical recurrence. Perinuclear antineutrophil cytoplasmic antibodies are linked to ulcerative colitis (UC) and are associated with a severe UC disease course, the need for surgery and (potentially) the response to therapy, but not disease activity. Serological antimicrobial antibodies are promising tools for the identification and prediction of risk for the development of complicated disease during the disease course in CD. To truly improve daily clinical practice serological antimicrobial antibodies need to be incorporated into clinical therapeutic trials to assess their role in identifying patients who may benefit from early immunosuppressive therapy.

Distinct Patterns of IgG and IgA against Food and Microbial Antigens in Serum and Feces of Patients with Inflammatory Bowel Diseases

“…The results of this and other studies raise several questions. For example, it remains not fully understood why Ab production towards distinct microbial and food antigens is differentially regulated, and why CD patients have elevated serum reactivity towards multiple microbial antigens [6] , [29] , whereas this phenomenon seems to be less obvious for UC patients, although the microbial load is much higher in the colon [8] . We may speculate that the association of microbial antigens with immune-stimulating molecules such as lipopolysaccharides and peptidoglycans have a major influence on their potential to induce adaptive immune responses.…”

Mechanisms, Management, and Treatment of Fibrosis in Patients With Inflammatory Bowel Diseases

“…Genetic variants encoding bacterial sensing receptors as well as serum antibodies against microbial components have been associated with the risk of intestinal fibrosis 58, 59 . Animal models do not develop intestinal fibrosis in the absence of a microflora 34 and in vitro data indicate a specific action of the bacterial protein flagellin in the fibrogenic response of intestinal mesenchymal cells 609 .…”

Fecal Eosinophil Cationic Protein Is a Diagnostic and Predictive Biomarker in Young Adults with Inflammatory Bowel Disease

“…pANCA and ASCA are independent of current disease activity, which is an advantage for their use in inactive patients with IBD. However, their general utility is hampered by the relatively low diagnostic accuracy [27].…”