Celiac disease is a T cell mediated immune disorder triggered by dietary gluten intake that affects approximately 1% of the US population and has significant deleterious effects on health and mortality. Small intestinal biopsy is the current gol standard for monitoring celiac disease activity but has limitations including invasiveness, expense and potential sampling error. As ongoing intestinal damage in celiac disease is common and clinically relevant, non-invasive tests of celiac disease activity and mucosal inflammation would be of great utility in both clinical practice and in research settings. Membrane microparticles (MPs) are 200-1000 nm diameter membrane bound vesicles that are generated from cell membranes. MPs have recently been shown to have an active role in cell signaling and to be promising disease biomarkers for of disorders including hepatic fibrosis, angiogenesis, coagulation and regulation of vascular tone. Despite promising data in other diseases, the ability of MPs to assess intestinal disorders has not been studied. We hypothesize that serum MPs have the potential to be valuable non-invasive biomarkers of celiac disease activity and our long-term goal is to define novel MP profiles for non-invasive monitoring of celiac disease activity.
The specific aims of our study are 1) to evaluate the relevant MP profile of active celiac disease and 2) to assess the utility of MP profiles for prediction of intestinal inflammation in celiac disease. Our preliminary data indicates that there are different MP profiles in active vs. treated celiac disease and different MP profiles in celiac disease compared with healthy controls. We are able to isolate MPs from serum using differential centrifugation followed by characterization with fluorescence-activated cell sorting (FACS) using standard cell surface markers. Further, our serum bank, containing samples from over 1000 individuals will allow for efficient and robust assessment of the utility of MPs in celiac disease. If MPs are found to be responsive and reliable markers of celiac disease activity, MP assessment may be quickly adopted into clinical practice and spur evaluation in other intestinal diseases for which a non-invasive biomarker is needed.
Celiac disease is one of the most common chronic inflammatory disorders in the United States. Despite great advances in our understanding of celiac disease, there is currently no validated tool for monitoring the activity of this common condition other than small intestinal biopsy. The aim of this project is to identify accurate non-invasive measures of celiac disease activity, which would be of great value in clinial practice, are prerequisite to the testing of new treatment modalities, and may offer insight into disease pathogenesis.
|Pallav, Kumar; Xu, Hua; Leffler, Daniel A et al. (2016) Immunoglobulin A deficiency in celiac disease in the United States. J Gastroenterol Hepatol 31:133-7|
|Lebwohl, Benjamin; Leffler, Daniel A (2015) Exploring the Strange New World of Non-Celiac Gluten Sensitivity. Clin Gastroenterol Hepatol 13:1613-5|
|Adriaanse, Marlou; Leffler, Daniel A (2015) Serum markers in the clinical management of celiac disease. Dig Dis 33:236-43|
|Pimentel, Mark; Morales, Walter; Rezaie, Ali et al. (2015) Development and validation of a biomarker for diarrhea-predominant irritable bowel syndrome in human subjects. PLoS One 10:e0126438|
|Tian, Na; Messana, Irene; Leffler, Daniel A et al. (2015) Salivary proline-rich proteins and gluten: Do structural similarities suggest a role in celiac disease? Proteomics Clin Appl 9:953-64|
|Kelly, Ciarán P; Bai, Julio C; Liu, Edwin et al. (2015) Advances in diagnosis and management of celiac disease. Gastroenterology 148:1175-86|
|Kabbani, Toufic A; Kelly, Ciaran P; Betensky, Rebecca A et al. (2013) Patients with celiac disease have a lower prevalence of non-insulin-dependent diabetes mellitus and metabolic syndrome. Gastroenterology 144:912-917.e1|
|Leffler, Daniel; Schuppan, Detlef; Pallav, Kumar et al. (2013) Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease. Gut 62:996-1004|
|Ludvigsson, Jonas F; Leffler, Daniel A; Bai, Julio C et al. (2013) The Oslo definitions for coeliac disease and related terms. Gut 62:43-52|
|Pallav, Kumar; Leffler, Daniel A; Bennett, Michael et al. (2012) Open conformation tissue transglutaminase testing for celiac dietary assessment. Dig Liver Dis 44:375-8|
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