Endotyping Immune Mediated Inflammatory Diseases

Ulcerative colitis (UC) is one such IMID where phenotypic classifications currently do not capture established immune cell heterogeneity. We have now demonstrated an ability to apply evolving spatial transcriptomics approaches to potentially re-classify phenotypically similar individuals based on their tissue immune cell profiles. In this proposal we seek to further advance this research by studying evolutions in immune cell profiles with various mechanism specific biologics and small molecules and aim to identify immune cell specific pathways of treatment resistance or response. We anticipate this will serve as a framework for broader collaborations around other IMIDs. Cohort: Moderate-severe (Mayo endoscopic sub-score 2-3, scored by an expert IBD provider, with consideration for re-review of available endoscopic videos for confirmation) UC patients being treated with:  Ozanimod (n=20) S1P receptor Modulator, BMS (Celgene)  Infliximab (n=20) TNF, Janssen  Vedolizumab (n=20) α4β7 integrin, Millennium/Takeda  Ustekinumab (n=20) IL12/23, Janssen Each treatment group will be further divided into responders and non-responders based on the following definition:  Non-responder: Persistent clinical (rectal bleeding, stool frequency) and endoscopic (Mayo endoscopic sub-score of 2-3) disease activity with confirmed adequate drug levels for biologics.  Responders: Mayo rectal bleeding and stool frequency sub-scores of 0, and endoscopic sub-score of 0. Geboes histologic score of < 3.2.