Tu1118 Non-Invasive Determination of Disease Activity in Ulcerative Colitis by Serum Luminex Profiling

Abstract

Background: In a previous study utilizing multiplex Luminex technology in a cohort of control and ulcerative colitis (UC) patients, we identifiedmultiple proinflammatory cytokines/ chemokines that were increased in the serum and tissue of patients with active UC, determined by histology, compared to control patients. In order to better assess the potential for Luminex profiling for clinical trials, our aim was to investigate the relationship between a validated clinical disease activity tool, the Mayo Disease Activity Index (DAI) and the endoscopy score (ES) subset of the DAI, and the cytokine/chemokine profile in UC patients. Methods: Human serum and colon tissue samples were collected prospectively from 40 control subjects undergoing screening colonoscopy and 137 UC patients. The DAI (a combination of stool frequency, blood in the stool, physician global assessment, and ES) was assessed for UC patients at the time of colonoscopy. Serum and tissue cytokines/chemokines were measured by a 39-plex MILLIPLEX bead assay. We classified UC patients by DAI or ES alone into inactive (DAI 0-2; ES 0) and active (DAI 3-12; ES 1-3) disease. Cytokine/chemokine levels were analyzed based upon the DAI and ES classifications and were compared to control patients. We also assessed the correlation of DAI with the serum and tissue cytokine/ chemokine levels. Results: When active versus inactive UC was defined by a DAI cutoff of 3 or greater, patients with active UC had increased serum levels of eotaxin-1, G-CSF, GMCSF, IL-8, and TGF-α compared to control patients (all with at least p,0.05). None of the tissue or serum cytokine/chemokine levels resulted in a correlation greater than an r2 value of 0.18 with DAI as a continuous variable. When active disease was defined by an ES of 1 or greater, serum eotaxin-1, G-CSF, GM-CSF, IL-8, and IL-9 levels were increased in active UC (all p,0.05). Eotaxin-1, GM-CSF, and IL-8 were also increased in tissues when compared to controls when active UC was defined by either increased DAI or ES. In total, there were 21 of 39 cytokines/chemokines increased in tissues from patients with a DAI of 3 or greater vs. normal control subjects, and 20 were increased when ES was used. In active vs. inactive UC by DAI or ES, there were increases in serum levels of G-CSF, IFNγ, and IL-8; IL-15 and TGF-α were also increased when active UC was defined by DAI. In active vs. inactive UC defined by DAI, there were 17 analytes increased in tissues. When defined by ES, there were 22 analytes increased, including eotaxin-1, G-CSF, and IL-8. Conclusions: Luminex profiling was robust in identifying active disease defined by using either the DAI or the ES. Testing for serum cytokines/chemokines, especially G-CSF, IL-8, and eotaxin-1, may represent a non-invasive strategy for detecting active UC that compares favorably with current clinical tools.