Malassezia Immune Responses as Biomarkers of IBD

PROJECT SUMMARY/ABSTRACT Inflammatory bowel disease (IBD) is the result of a dysregulated inflammatory immune response in the mucosa of the gastrointestinal tract. The disease is associated with alterations in the permeability of the intestinal epithelia and changes in the intestinal microbiota. Rather than being a single disease, or two diseases (Crohn's disease or ulcerative colitis), IBD is increasingly understood as a multifaceted disease that is initiated and exacerbated by influences such as genetic susceptibility, environmental factors such as diet and smoking, differing immune responses, and alterations in the intestinal microbiota. A major goal in IBD research and care is to improve outcomes by targeting disease treatment to an individual patient's specific underlying disease mechanism(s). Serum antibodies are proving to be a leading biomarker for diagnosing and discriminating IBD patients. The most commonly used serological antibody markers are Perinuclear Anti-neutrophil Cytoplasmic Antibodies (pANCA) and Anti-Saccharomyces Cerevisiae Antibodies (ASCA). In this proposal we identify anti-Malassezia lipase antibodies (AMLAb) as a novel biomarker that identifies a substantial subset of patients with IBD. We hypothesize elevated AMLAb levels reflect “types” of disease that share underlying mechanisms. To investigate this, we propose 3 aims that focus on 1) identifying shared clinical and genetic features of IBD patients positive for AMLAb, 2) assessing the impact of AMLAb on innate immune responses to Malassezia and identifying features of disease that promote AMLAb, and 3) assessing the link between AMLAb and anti-Malassezia T cell responses that we have also discovered to be common in these patients and the role of these T cells in the gut mucosa. Completion of this study will shed light on mechanisms underlying development and persistence of IBD and will suggest new ways to tailor treatments for these patients.