(17) Systemic inflammation in pre-diagnostic ulcerative colitis
Daniel Bergemalm (1), Erik Andersson (1), Pontus Karling (2), Stephen Rush (3), Carl Eriksson (1), Dirk Repsilber (3), Johan Hultdin (4) and Jonas Halfvarson (1).
(1) Deptartment of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden, (2) Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden (3) School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden , (4) Department of Medical Biosciences, Division of Clinical Chemistry, Umeå University, Umeå, Sweden
Background: We aimed to characterize the systemic pre-diagnostic inflammation in ulcerative colitis (UC), using a comprehensive set of protein markers.
Method: Plasma samples from individuals (n=72) who later in life developed UC and matched healthy controls (n=140), were identified from a population-based screening cohort. Ninety-two inflammatory protein markers were quantified using proximity extension assay. To examine their biological relevance, findings were validated in an inception cohort of treatment-naïve, UC patients (n=101) and healthy controls (n=50). Ultimately, to examine the impact of shared genetic and environmental factors, a cohort of healthy mono- and dizygotic twin siblings of UC patients (n=41) and matched healthy controls (n=37) were explored.
Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP1) were significantly upregulated (p<0.05) in pre-diagnostic UC compared to matched healthy controls. Using receiver operating curve, a prediction model using the six proteins discriminated newly diagnosed, treatment naïve UC cases from healthy controls (AUC=0.96; CI 0.93-0.98). An AUC of 0.73 (CI 0.62-0.84) was observed when the model was applied to healthy twin siblings (n=41) vs. healthy controls. Protein upregulations were more pronounced at diagnosis of UC compared to in pre-diagnostic samples and healthy twin siblings.
Conclusions: This is the first comprehensive characterisation of pre-diagnostic systemic inflammation in UC. Significant proteins of inflammation were upregulated several years prior to diagnosis as well as in disease. Proteins were similarly regulated in healthy twin siblings of UC patients implying impact of genetic and environmental factors. Characterisation of the pre-diagnostic stage of UC could pave the way for identification of predictive biomarkers and preventive strategies.