Abstract
Stricturing and penetrating disease are classified as severe Crohn’s disease types and are frequently associated with an increased risk for bowel surgery. Research has shown that early treatment with aggressive immunosuppression (including biological and thiopurine therapies – the so-called “top-down approach”) results in a diminished risk of developing these complicated disease types. However, these therapies carry significant risks and cost. Being able to predict which patients are at an increased risk of developing severe Crohn’s disease may enable us to treat patients individually, with the aggressive “top-down approach” started at diagnosis in patients with a significantly increased risk of developing complicated disease types. Defects of innate and adaptive immunity both play a role in Crohn’s disease pathophysiology. Identifying whether defects of innate immunity (through gene mutations) or adaptive immunity (through antibodies to microbial antigens) are associated with stricturing/penetrating disease types may enable us to predict the course of the disease and therefore decide on who would benefit most from the “top-down approach”. This review discusses the role of NOD2 and other gene polymorphisms in predicting Crohn’s disease severity. It also highlights the evidence linking the role of the various antibodies involved in adaptive immunity (ASCA, OmpC, GM-CSF) and complicated Crohn’s disease types.
Highlights
The Montreal classification of inflammatory bowel disease classifies Crohn’s disease (CD) into three disease types: inflammatory disease, stricturing disease and penetrating disease [1]
Defects of innate and adaptive immunity both play a role in CD pathophysiology (Figure 1) and identifying whether defects of innate immunity or adaptive immunity are associated with stricturing/penetrating disease types may be used to predict the course of the disease
This review focuses on biomarkers which may be used to predict the development of delayed complicated disease types in Crohn’s, enabling us to identify which of these patients would benefit most from early, aggressive immunosuppression
Summary
The Montreal classification of inflammatory bowel disease classifies Crohn’s disease (CD) into three disease types: inflammatory (nonstricturing, non-penetrating) disease, stricturing disease and penetrating disease [1]. Since using potent immunosuppressants in all CD patients may expose patients with mild CD to an increased risk of side-effects from these immunomodulators and biological agents, this approach may help identify which patients would benefit from aggressive immunosuppression at an early stage This approach is frequently called the “top-down” approach and involves starting intensive therapies, including biological agents (anti-tumor necrosis factor α agents like infliximab) early on with the aim of avoiding the development of strictures and fistulas. Defects of innate and adaptive immunity both play a role in CD pathophysiology (Figure 1) and identifying whether defects of innate immunity (through gene mutations) or adaptive immunity (through antibodies to microbial antigens) are associated with stricturing/penetrating disease types may be used to predict the course of the disease This may enable physicians to choose “tailor-made” therapy for their CD patients at the time of diagnosis.
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