The contact activation system and ulcerative colitis
This prospective study characterizes the plasma contact activation system in patients with ulcerative colitis (UC). We expect to find new biomarkers that may replace stool samples, reduce the number of endoscopies and predict a UC relapse in it's early stage.
It is important to detect relapses of ulcerative colitis (UC) as soon as possible. Since early treatment decreases the risk of short- and longterm complications i.e. hospitalization, surgery, low quality of life, tromboembolism and cancer.
Clinicians typically evaluate UC activity by lower endoscopy or fecal calprotectin combinated with symptoms and c-reactive protein levels. Both endoscopy and fecal calprotectin are less patient friendly, and endoscopy may cause complications. Therefore it is of great interest to find a more sensitive and specific "UC" biomarker, which is available as a blood analysis. This may replace stool samples and reduce the number of endocopies.
We expect the contact activation system (CAS) may provide such a biomarker. CAS mediates inflammation through the release of bradykinin, which influences endothelial and neutrophil function. Potential activators of CAS are activated coagulations factor XII, neutrophil elastase and misfolded proteins, i.e. proteins who's native structure have changed.
Patients with UC is suspected to accumulate misfolded proteins which is harmful to the cells. It is demonstrated that CAS function during active UC differs from that during inactive phase. It is also demonstrated that neutrophil products correlate with UC i.e. fecal calprotectin and to a lesser extend elastase. The elastase inhibitor, alfa-1-antitrypsin is a protein. When it misfolds, it looses its function. A condition that may be associated with increased risk of UC.
The hypothesis: Active UC is characterized by increased activity of CAS which may be caused and/or sustained by misfolded proteins.
- To quantify the plasma CAS activity in patients with active UC and compare this with that of healthy individuals.
- To describe changes in CAS activity by comparing active and inactive UC stages, across plasma, stool and colonic tissue samples.
- To quantify the amount of misfolded alfa-1-antitrypsin.
Description of the cohort
A cohort of 102 adults with active UC is enrolled at the Department of Medical Gastroenterology, University Hospital of Southern Denmark. They are followed for 26 weeks (5 visits). UC treatment follows current guidelines. Active UC is defined by a simple clinical colitis activity index >=5 and a Mayo score >=1.
Exclusion criteria are factors that may cause inflammation or influence CAS activity i.e. pregnancy, infection, specific inflammatory disorders incl. cancer, chronic liver, heart and renal failure; medication with prednisone, ace inhibitors and specific types of anti-coagulantia.
Data and biological material
- Demographics (age, sex, comorbidity, medication, and duration, onset, location and severity of UC)
- Questionnaires (simple clinical colitis activity index, patient reported outcome 2 and short inflammatory bowel disease questionnaire)
- Blood (EDTA and citrate), feces (extract and stool), and fixated colonic tissue samples (formalin and snap frozen)
Collaborating researchers and departments
The Unit of Thrombosis Research, University Hospital of Southern Denmark
- Johannes Jakobsen Sidelmann
Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University Hospital of Southern Denmark
Division LAB, CDL Research, University Medical Center Utrecht
Department of Clinical Pathology, University Hospital of Southern Denmark