Profiling and Perturbing the Human Immune System to Understand the Human Immune Network

This study aims to compare IBD patients with healthy controls to obtain a systems-level view of immune system perturbation by IBD. This intervention (anti-TNF therapy) will be intended to treat IBD but will also represent a major, broad immune system perturbation. Although the response of the patient in terms of disease changes will be of considerable interest, the focus here will be on broader immune system perturbation by immune-targeting drugs. Similarly, we will take advantage vaccinations routinely prescribed to IBD patients to further study the effects of a defined perturbation on overall immune homeostasis. By studying this IBD cohort, we will be able to interrogate (1) the initial response to immune system perturbations in comparison to other cohorts in the Allen Institute projects; (2) homeostatic equilibrium of these treatments; (3) and loss of homoeostasis. We will enroll patients with Crohns disease or ulcerative colitis. These patients will be anti-TNF naïve, defined as no prior treatment with anti-TNF drugs (or other biologics); or at least 3 months since the last treatment with anti-TNF drugs (or other biologics); or currently on anti-TNF therapy (or other biologic) but with high levels of anti-drug antibodies and undetectable drug level. Such patients will be enrolled prior to initiation of anti-TNF therapy, and subsequent initiation of such therapy will represent a major immune perturbation. Following enrollment, patients (and healthy control subjects) will be vaccinated with IFV and/or pneumococcal vaccine based on established clinical guidelines, and these vaccinations will serve as secondary immune system perturbations.