Antibodies in the exploration of inflammatory bowel disease pathogenesis and disease stratification

Abstract

Normal mucosal homeostasis is the interdependent relationship of epithelium, luminal microorganisms, and the regional immune system (Fig. 1). This tripartite relationship has particularly evolved during the eutherian period, due to the emergence of a dynamic, antigen-specific immune system [1, 2]. The mammalian immune system has an exceptional capacity for specific antigen recognition and immunologic memory to microibal antigens, and for powerful amplification of effector mechanisms against such antigenic targets [3, 4]. These properties obviously require special adaptation to preserve the mucosal-microbial interrelationship essential for normal intestinal function. It is widely understood that inflammatory bowel disease (IBD) involves a chronic disturbance in this homeostasis. In recent years there has been a particular effort to understand this homeostatic disturbance in the context of immunologic activation and tissue damage. In particular, this effort has been informed by the emerging understanding of Helicobacter pylori pathogenesis in peptic ulcer disease. From this precedent we have learned that the manifestation of clinical disease reflects the interplay of commensal bacterial and host traits, which together affect levels of colonization, and the nature and intensity of inflammation and tissue damage [5, 6]. Our review focuses on the insights provided by IBD-associated antibodies on disease pathogenesis and clinical stratification. We will first consider the nature of immunologic quiescence in the mucosa. We will then assess the concepts and experimental issues regarding disease-related antibodies and their antigenic targets. This will be followed by an analysis of the microbial antigens and autoantigens identified by IBD-related antibodies. Finally, we will discuss how these antibodies and antigens are being applied to issues of disease diagnosis, clinical stratification, and strategies for treatment. © 2005 Springer Science+Business Media, Inc.