1. Interrogating host immunity to predict treatment response in inflammatory bowel disease
- Author
-
Nick Powell, Giovanni Monteleone, Raja Atreya, and Jonathan Digby-Bell
- Subjects
0301 basic medicine ,Intravital Microscopy ,Bioinformatics ,Inflammatory bowel disease ,Endoscopy, Gastrointestinal ,DOUBLE-BLIND ,ACTIVE ULCERATIVE-COLITIS ,0302 clinical medicine ,Maintenance therapy ,SEVERE CROHNS-DISEASE ,Cell Movement ,FECAL MICROBIOTA TRANSPLANTATION ,Lymphocytes ,Precision Medicine ,TUMOR-NECROSIS-FACTOR ,Settore MED/12 - Gastroenterologia ,Microscopy, Confocal ,Innate lymphoid cell ,Gastroenterology ,FACTOR-ALPHA ,INDUCTION THERAPY ,Prognosis ,Immunohistochemistry ,Treatment Outcome ,Cytokines ,030211 gastroenterology & hepatology ,Life Sciences & Biomedicine ,medicine.drug ,Signal Transduction ,MAINTENANCE THERAPY ,INNATE LYMPHOID-CELLS ,Vedolizumab ,03 medical and health sciences ,Immune system ,Gastrointestinal Agents ,Ustekinumab ,medicine ,Humans ,GENOME-WIDE ASSOCIATION ,Janus Kinases ,Science & Technology ,Tofacitinib ,Gastroenterology & Hepatology ,Hepatology ,business.industry ,Gene Expression Profiling ,medicine.disease ,Precision medicine ,Inflammatory Bowel Diseases ,030104 developmental biology ,Tumor Necrosis Factor Inhibitors ,business - Abstract
IBD treatment is undergoing a transformation with an expanding repertoire of drugs targeting different aspects of the immune response. Three novel classes of drugs have emerged in the past decade that target leukocyte trafficking to the gut (vedolizumab), neutralize key cytokines with antibodies (ustekinumab) and inhibit cytokine signalling pathways (tofacitinib). In advanced development are other drugs for IBD, including therapies targeting other cytokines such as IL-23 and IL-6. However, all agents tested so far are hampered by primary and secondary loss of response, so it is desirable to develop personalized strategies to identify which patients should be treated with which drugs. Stratification of patients with IBD by clinical parameters alone lacks sensitivity, and alternative modalities are now needed to deliver precision medicine in IBD. High-resolution profiling of immune response networks in individual patients is a promising approach and different technical platforms, including in vivo real-time molecular endoscopy, tissue transcriptomics and germline genetics, are promising tools to help predict responses to specific therapies. However, important challenges remain regarding the clinical utility of these technologies, including their scalability and accessibility. This Review focuses on unravelling some of the complexity of mucosal immune responses in IBD pathogenesis and how current and emerging analytical platforms might be harnessed to effectively stratify and individualise IBD therapy. IBD treatment has an expanding repertoire of drugs targeting different aspects of the immune response. This Review focuses on unravelling the complexity of mucosal immune responses in IBD pathogenesis and how analytical assays might be harnessed to effectively stratify and individualise IBD therapy.
- Published
- 2019