Systematic transethnic profiling of anticytokine and anti-leukocyte trafficking for the detection of drug-specific response signatures in the treatment of inflammatory bowel disease.

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Inflammatory bowel disease (IBD) is a common, chronic, immune-mediated barrier disease. Current therapeutic interventions with anti-cytokine antibodies (TNF-a, IL-23/IL-12) reflect the intent to disrupt specific pathways of inflammatory immunopathology. Individual responses to biological treatment can thereby be exploited in a systems biology approach that employs a targeted mechanism of action (MOA) to decipher molecular signatures of therapeutic responses in the context of a distinct disease entity to describe common and unique transcriptional signatures of disease and drug-response. Using a translational approach (including whole exorne sequencing of DNA and whole transcriptome sequencing of RNA from peripheral blood mononuclear cells and mucosal biopsies, identifying drugspecific alterations of the gut microbiota before and at indicated time-points after drug administration) to investigateclinical and molecular phenotypes during therapeutic interference with cytokine signaling and leukocyte trafficking, we aim to trace common and unique signatures of drug- and therapy-specific responses. By comparing response signatures in a german and chinese population we aim to decipher genetic and environmental factors that influence individual drug- response in a diseased organ.