Towards personalized care in IBD

Abstract

The expanding knowledge of the role of genetic variants involved in the susceptibility to IBD heralds an era of disease categorization beyond Crohn's disease and ulcerative colitis. A more robust molecular definition of the spectrum of IBD subtypes is likely to be based on specific molecular pathways that determine not only disease susceptibility but also disease characteristics such as location, natural history and therapeutic response. Evolving diagnostic panels for IBD will include clinical variables and genetic markers as well as other indicators of gene function and interaction with environmental factors, such as the microbiome. Multimodal algorithms that combine clinical, serologic and genetic information are likely to be useful in predicting disease course. Variation in IBD-susceptibility and drug-related pathway genes seems to influence the response to anti-TNF therapy. Furthermore, gene expression signatures and composite models have both shown promise as predictors of therapeutic response. Ultimately, models based on combinations of genotype and gene expression data with clinical, biochemical, serological, and microbiome data for clinically meaningful subgroups of patients should permit the development of tools for individualized risk stratification and treatment selection.

Epithelial EZH2 serves as an epigenetic determinant in experimental colitis by inhibiting TNFα-mediated inflammation and apoptosis

“…Among the cytokines implicated in colitis, TNFα is the best studied, and its overproduction is a hallmark of IBD. Thus, anti-TNFα therapies have been adopted to reduce inflammatory responses and apoptosis in the treatment of IBD (10). As a pleiotropic cytokine, TNFα not only induces IEC apoptosis by inducing the cleavage of caspase 8 or PUMA (11), but also stimulates NF-κB signaling to augment the immune response.…”

How the Discovery of TNF-α Has Advanced Gastrointestinal Diseases and Treatment Regimes

“…The success of these anti-TNF-a agents has nonetheless drastically changed treatment protocols for patients with UC and CD, with clinical remission more probable than with agents used previously. A future challenge is to use biomarkers to help select patient's response to powerful, targeted therapies such as anti-TNF agents [37,38]. Yet, since their use is associated with undesirable adverse effects such as development of intolerance and increased infection risk, further research into how TNF-a is involved in IBD pathogenesis is still warranted to uncover mechanisms that could provide novel therapeutic targets.…”

Personalizing IBD Therapy: The Asian Perspective

“…Serological markers may be more useful in predicting the clinical course of IBD than in diagnosis or differentiation [8] . Seropositivity for ASCA and other antimicrobial antibodies, such as antibodies to CBir1, OmpC and I 2 , is associated with complications such as strictures, fistulas and abdominal surgery [3] . pANCA seropositivity may predict refractory UC as well as pouchitis after total proctocolectomy with ileal pouch-anal anastomosis [12] .…”

“…Serological markers, whether applied alone or in combination, are highly specific but not sensitive for IBD. Therefore, they are of limited value in population screening [3] . Serological markers may be more useful in predicting the clinical course of IBD than in diagnosis or differentiation [8] .…”

“…Clinical predictors of poor prognosis in Crohn's disease (CD) include young age at diagnosis, perianal disease, ileal location, extensive small bowel involvement, stricturing or penetrating behavior at diagnosis, need for steroids, deep colonic ulcers and smoking [3][4][5] . These clinical characteristics predict poor outcomes in terms of complications, surgery, relapse and disabling disease.…”