P152 Longitudinal immune profiling of peripheral blood in patients with Ulcerative Colitis

Abstract

Abstract Background Recent literature has established the communication and mutual influence between the gut and the brain, referred to as the gut-brain axis. While inflammatory bowel disease (IBD) poses a risk for neuroinflammation and brain dysfunction, the molecular mechanisms are not fully understood. This study aims to investigate longitudinal changes during Ulcerative Colitis (UC), focusing first on the characterization of peripheral immune cell subsets, circulating cytokines, and extracellular vesicles (EVs). Methods In our study, we examined 19 UC patients in both active (mean age in years: 45,63) and remission phases (mean age in years: 46,16). A gastroenterologist at the Gastroenterology Department from the Otto-von-Guericke University in Magdeburg, Germany assessed all participants, categorizing them into stages using Mayo scoring and calprotectin levels. We analysed peripheral whole blood and plasma samples using different flow cytometry-based approaches. Results Our findings indicate an upregulation of the neutrophil (CD16+, CD15+) numbers during the active stage followed by a significant reduction during remission, indicating an increase in innate inflammation as a first line of defence and a balanced state during remission. Classical (CD14+, CD16-) monocytes were decreased, along with similar results in the intermediate (CD14+, CD16+) subset. Nonclassical monocytes (CD14+, CD16++) increased from the active to the remission stage. Surface expression of activation marker CCR2 was downregulated for all monocyte subsets, whereas CX3CR1 was upregulated specifically in intermediate monocytes during remission. Compared to the active stage peripheral dendritic cell (CD14-, CD16-) numbers increase during remission suggesting less colonic infiltration. Peripheral regulatory T cells (Tregs) (CD127 low/-, CD25+), which are important for the reestablishment of homeostasis are upregulated during remission. Characterization of cytokine levels in plasma revealed an upregulation of the proinflammatory milieu during the active stage, especially with elevated IL-18 and TGF- β1 levels. Finally, those changes were accompanied by alterations of the surface markers expressed by isolated circulating EVs. Conclusion Our initial results indicate the feasibility of evaluating the gut-brain axis through liquid biopsy. We unravel the composition of the peripheral inflammatory milieu during the active phase. Currently we are focusing on the assessment of the CNS-derived metabolites and their bidirectional communication with the gastrointestinal system.