SUPR
Characterization of UC1 and UC2 patients: towards personalized medicine in Ulcerative Colitis
Dnr:

NAISS 2024/6-116

Type:

NAISS Medium Storage

Principal Investigator:

Eduardo Villablanca

Affiliation:

Karolinska Institutet

Start Date:

2024-04-29

End Date:

2025-05-01

Primary Classification:

30110: Immunology in the medical area

Allocation

Abstract

Ulcerative Colitis (UC) is a chronic inflammatory bowel disease (IBD) that is usually confined to the colon. UC is highly heterogeneous, encompassing a wide range of patterns associated with behavior, location, and response to treatment. Despite this heterogeneity, patient classification criteria for tailored therapies are currently lacking. We have recently developed an unbiased stratification of UC patients (UC1/UC2) based on their transcriptomic profiles. UC1 patients are characterized by a low response (~10%) to biological therapies (infliximab/vedolizumab) and an increased expression of genes associated with neutrophil degranulation and cytokine signaling. Meanwhile, UC2 patients have a higher responsiveness to biological therapy (~60%), and low expression of genes associated with lack of response to anti-TNF treatment. Therefore, we hypothesize that this classification can be used towards the design of personalized medicine in IBD. However, to consolidate this novel classification for clinical practice, further characterization is needed. Using bulk and scRNA-seq from both publicly available and in-house generated datasets we aim to deeply characterize the immune cell composition and molecular pathways underpinning different UC subsets. This study will provide potential new mechanistic insights into the etiology of IBD and UC therapy management.