P0562 - Probing Predilection to Crohn's Disease and Crohn's Disease Flares: A Crowd-Sourced Bioinformatics Approach

Jihad Aljabban, MD, MMSc¹, Michael Rohr, BA², Eli Cohen, MD³, Naima Hashi, MD⁴, Vincent Borkowski, MD, PhD¹, Hisham Aljabban, BS⁵, Emmanuel Boateng, MD³, Saad Syed, MD⁶, Ali Mukhtar, BS⁷, Hajra Khan, MD⁸, Mary Nemer, MD⁹, Dexter Hadley, MD, PhD², Maryam Panahiazar, PhD^10
1University of Wisconsin Hospital and Clinics, Madison, WI; ²University of Florida College of Medicine, Orlando, FL; ³Vanderbilt University Medical Center, Nashville, TN; ⁴Mayo Clinic, Rochester, MN; ⁵Barry University, Grand Blanc, MI; ⁶Stanford University School of Medicine, Palo Alto, CA; ⁷Columbia University College of Physicians and Surgeons, New York, NY; ⁸Detroit Medical Center, Detroit, MI; ⁹University of Wisconsin School of Medicine and Public Health, Madison, WI; ¹⁰University of California San Francisco, San Francisco, CA

Introduction: Crohn’s Disease (CD) is an inflammatory disease of the gastrointestinal tract that affects millions of patients. While great strides have been made in treatment, namely in biologic therapy such as anti-TNF drugs, CD remains a significant health burden.

Methods: We conducted two meta-analyses using our STARGEO platform to tag samples from Gene Expression Omnibus. One analysis compares inactive colonic biopsies from CD patients (39) to colonic biopsies from healthy patients (30) as a control and the other compares colonic biopsies from active CD lesions (65) to inactive lesions (39). Results from the two meta-analyses were analyzed using Ingenuity Pathway Analysis.

Results: For the inactive CD vs healthy tissue analysis, we noted FXR/RXR and LXR/RXR activation, superpathway of citrulline metabolism, and atherosclerosis signaling as top canonical pathways. The top upstream regulators include genes implicated in innate immunity, such as TLR3 and HNRNPA2B1, and sterol regulation through SREBF2. In addition the sterol regulator SREBF2, lipid metabolism was the top disease network identified in IPA (fig1). Top upregulated genes hold implications in innate immunity (DUOX2, REG1A/1B/3A) and cellular transport and absorption (ABCG5, NPC1L1, FOLH1, and SLC6A14). Top downregulated genes largely held roles in cell adhesion and integrity, including claudin 8, PAQR5, and PRKACB.

For the active vs inactive CD analysis, we found immune cell adhesion and diapedesis, hepatic fibrosis/hepatic stellate cell activation, LPS/IL-1 inhibition of RXR function, and atherosclerosis as top canonical pathways. Top upstream regulators included inflammatory mediators LPS, TNF, IL1B, and TGFB1. Top upregulated genes function in the immune response such as IL6, CXCL1, CXCR2, MMP1/7/12, and PTGS2. Downregulated genes dealt with cellular metabolism and transport such as CPO, RBP2, G6PC, PCK1, GSTA1, and MEP1B.

Discussion: Our results build off long-described players in CD pathogenesis and provide more support for more recently described genes such as FXR, RXR, and the ribonucleo-protein HNRNPA2B1, among our other findings. Additionally, identification of SREBF2, involved in cholesterol homeostatsis, as a top usptream regulator and lipid metablosim as a top disease network suggests a role of lipid proifles in CD risk. Overall, this study provides more insight to CD and possibile therapeutic targets.



Disclosures:


Jihad Aljabban, MD, MMSc¹, Michael Rohr, BA², Eli Cohen, MD³, Naima Hashi, MD⁴, Vincent Borkowski, MD, PhD¹, Hisham Aljabban, BS⁵, Emmanuel Boateng, MD³, Saad Syed, MD⁶, Ali Mukhtar, BS⁷, Hajra Khan, MD⁸, Mary Nemer, MD⁹, Dexter Hadley, MD, PhD², Maryam Panahiazar, PhD¹⁰. P0562 - Probing Predilection to Crohn's Disease and Crohn's Disease Flares: A Crowd-Sourced Bioinformatics Approach, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.