Exploring the Impact of Gut Neutrophil Heterogeneity on Clinical Response of IBD Patients to anti-TNF _ Biologic

Patients with inflammatory bowel diseases (IBD) require timely and efficacious therapeutic intervention. When conventional medications such as corticosteroids or 5-aminosalicylates fail to alleviate the disease, biologics that block a critical inflammatory molecule called tumor-necrosis-factor alpha (TNF_) are commonly used. Several drugs targeting TNF_ are currently used to treat IBD, which include Infliximab, Adalimumab, Etanercept, and Certolizumab Pegol. Unfortunately, one third of treated patients still fail to respond to these drugs. We and others have established in the past a role of immune cells called Neutrophils in IBD pathology. Neutrophils are professional phagocytes with primary role in bacterial killing and host defense; however, they also shape the inflammatory environment in the colon and are responsible for IBD disease severity. More recent studies have correlated Neutrophil presence and activity in the colon with reduced therapeutic response. Importantly, we and others have identified diverse neutrophil subsets in inflamed tissue with both protective and detrimental functions. Thus, the goal of this study is to use state of the art molecular and genetic tools to establish whether distinct Neutrophil subsets drive unresponsiveness to TNF_ biologics and define specific gene signatures that can help predict clinical response and aid in designing of future therapeutics to maintain durable clinical response in severe IBD.