A91 NOVEL TRIM22 INTERACTIONS REVEAL POTENTIAL CAUSATIVE MECHANISMS IN VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE (VEOIBD)

摘要

BackgroundThe severe multi-systemic phenotype of VEOIBD is often difficult to treat with conventional therapies. Causative monogenic mutations have been identified, but the majority of VEOIBD patients present without any known defect. Our recently published whole exome sequencing (WES) of VEOIBD patients identified autosomal recessive variants in antiviral E3 ubiquitin ligase TRIM22, identifying its novel role in NOD2 signal regulation through interaction and ubiquitination of NOD2. TRIM22 patient variants caused aberrant NOD2 antiviral and pro-inflammatory signalling. TRIM22’s role in these pathways, and roles TRIM proteins play in proliferation and apoptosis, inspires confidence in its critical role in VEOIBD. However, the complete range of pathways influenced by TRIM22 remains a mystery.