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Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.com 06/21/2017 - Circulating gluten-specific FOXP3+CD39+ regulatory T cells have impaired suppressive function in patients with celiac disease. What does that mean? Although researchers understand the effector T-cell response in patients with celiac disease pretty well, they really don't know very much about the role played by regulatory T cells (Treg cells) in the loss of tolerance to gluten. To get a better picture, a team of researchers recently set out to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3)+ Treg cells. The research team included L Cook, CML Munier, N3 Seddiki, D van Bockel, N Ontiveros, MY Hardy, JK Gillies, MK Levings, HH Reid, J Petersen, J Rossjohn, RP Anderson, JJ Zaunders, JA Tye-Din, AD Kelleher. For the study, gluten-free patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. The research team collected peripheral blood before and after challenge. To effectively measure the gluten-specific CD4+ T-cell response, they combined traditional IFN-γ ELISpot with a test for antigen-specific CD4+ T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation, but relies instead on antigen-induced co-expression of CD25 and OX40 (CD134). During the gluten challenge, levels of circulating gluten-specific Treg cells and effector T cells both rose sharply, peaking on the sixth day. The team recounts surprise on discovering that about 80% of the ex vivo circulating gluten-specific CD4+ T cells were FOXP3+CD39+Treg cells, which reside within the pool of memory CD4+CD25+CD127lowCD45RO+ Treg cells. Even though they saw normal suppressive function in peripheral polyclonal Treg cells from celiac patients, after a short in vitro expansion, the gluten-specific FOXP3+CD39+ Treg cells showed sharply reduced suppressive function compared with polyclonal Treg cells. The team's study offers the first estimates of FOXP3+CD39+ Treg cell frequency within circulating gluten-specific CD4+ T cells after oral gluten challenge of celiac patients. FOXP3+CD39+ Treg cells made up the majority of all circulating gluten-specific CD4+ T cells, but they showed reduced suppressive function, indicating that Treg cell dysfunction might be a key factor in celiac disease development. This type of research is crucial to help document the genetic physiology of celiac disease, which will help researchers to better understand and treat the disease itself. Source: J Allergy Clin Immunol. 2017 Mar 8. pii: S0091-6749(17)30343-3. doi: 10.1016/j.jaci.2017.02.015. The researchers are variously affiliated with the Immunovirology and Pathogenesis Program, The Kirby Institute, UNSW Sydney, Sydney, Australia, St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, Australia; the Infection and Immunity Program, The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Australia; the Immunovirology and Pathogenesis Program, The Kirby Institute, UNSW Sydney, Sydney, Australia; St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, Australia, Immunology Division, Walter and Eliza Hall Institute, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia; Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; the Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom; the Immunology Division, Walter and Eliza Hall Institute, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia; ImmusanT, Cambridge, Massachusetts; and the Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Australia.
Jefferson Adams posted an article in Liver Disease and Celiac DiseaseCeliac.com 09/01/2015 - Current medical guidelines recommend routine screening of liver function tests (LFTs) in patients diagnosed with celiac disease. However, there isn't much good data on rates of liver disorders in celiac disease outside of Europe. A team of researchers recently set out to accurately estimate rates of LFT abnormalities in celiac disease in the USA, and to assess the effect of a gluten-free diet on LFTs. The research team included Natalia E Castillo, Rohini R Vanga, Thimmaiah G Theethira, Alberto Rubio-Tapia, Joseph A Murray, Javier Villafuerte, Alan Bonder, Rupa Mukherjee, Joshua Hansen, Melinda Dennis, Ciaran P Kelly and Daniel A Leffler. To identify adult patients with biopsy-proven celiac disease, they used a prospectively maintained database, which they matched with healthy controls. They defined abnormal LFT levels for women and men based on the Third National Health and Nutrition Examination Survey (NHANES III) criteria. The team gathered data on demographics, coexisting liver diseases, and laboratory work-ups including aspartate transaminase (AST) and alanine transaminase (ALT) values at the time of diagnosis and on a gluten-free diet. They later compared data from this group with data from 7,789 individuals participating in the National Health and Nutrition Examination Survey, 2009–2010, and applied univariate logistic regression, Wilcox on signed-ranks, Student's t-test, χ2, and Fischer's exact test for statistical analysis. In 463 celiac disease patients with ALT or AST levels at the time of celiac disease diagnosis, 40.6% had elevated LFTs compared with 24.2% of treated celiac disease patients (P<0.001). Similarly, nearly forty percent of celiac disease patients on the NHANES database showed abnormal ALT values compared with less than twenty percent of non-celiac patients (P=0.03). Just over forty percent of individuals will show elevated LFTs at celiac disease diagnosis, but the vast majority, nearly eighty percent of those patients will show normal LFTs within a year and a half of adopting a gluten-free diet. The team suggests that doctors check all celiac patients for LFTs, and coexisting liver disorder be considered in patients whose LFTs have not improved within a year on a gluten-free diet. Source: The American Journal of Gastroenterology 110, 1216-1222 (August 2015). doi:10.1038/ajg.2015.192
Jefferson Adams posted an article in Heart Failure and Celiac DiseaseCeliac.com 02/16/2015 - Celiac is predominantly a disease of the small intestine characterized by chronic malabsorption in genetically susceptible individuals who ingest grains containing. gluten, such as wheat, barley, and rye. Using strain and strain rate echocardiography imaging, a research team set out to assess left ventricular function in patients with celiac disease. The research team included S. Cenk, D.B. Aylin, A. Fatma Ebru, A.B. Nihal, Ö.S. Sevil, B. Serdal, B. Emine, A. Hüseyin, K. Telat, D. Tahir, E. Osman, and B. Engin. For their study, the team included twenty celiac patients and twenty healthy control subjects. They assessed left ventricle systolic and diastolic functions using standard 2-dimension, M-mode, conventional Doppler echocardiography. They obtained strain and strain rate parameters for 8 segments of the left ventricle. They found no significant differences between patients and controls regarding left ventricle function as assessed by 2-dimensional, M-mode, conventional Doppler. Initially, differences between strain rate values did not reach statistical significance, but when strain and average strain values were considered together, statistically significant differences emerged between the groups. For the first time a research team has been able to determine the subclinical effect of celiac disease on left ventricular systolic function by using strain echocardiography imaging. Their success shows the potential value of assessing cardiac involvement in celiac patients using these echocardiographic techniques. Source: Turk J Med Sci. 2014;44(2):173-7.
Jefferson Adams posted an article in Liver Disease and Celiac DiseaseCeliac.com 09/09/2013 - Many people with celiac disease show slightly elevated liver enzymes, though these enzyme levels usually return to normal after gluten-free diet. A team of researchers recently set out to investigate the cause and prevalence of altered liver function tests in celiac patients, basally and after 1 year of gluten-free diet. The research team included Giovanni Casella, Elisabetta Antonelli, Camillo Di Bella, Vincenzo Villanacci, Lucia Fanini, Vittorio Baldini, and Gabrio Bassotti. They are affiliated with the Medical Department, and the Clinical Pathology Department of Desio Hospital in Monza and Brianza, Italy, the Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology Section at the University of Perugia in Perugia, Italy, and with the Department of Laboratory Diagnostics, Pathology Section, Brescia, Italy. The team gathered data from 245 untreated celiac disease patients, 196 women and 49 men, ranging in age from 15 to 80 years. They then analyzed the data, and assessed the results of liver function tests performed before and after diet, as well as associated liver pathologies. They found that 43 (17.5%) of the 245 patients, showed elevated levels of one or both aminotransferases; In 41 patients (95%) the elevation was mild, meaning that it was less than five times the upper reference limit. The remaining two patients (5%) showed marked elevation, meaning levels more than ten times the upper reference limit. After patients eliminated gluten for one year, aminotransferase levels normalized in all but four patients, who had HCV infection or primary biliary cirrhosis. Celiac patients who show hypertransaminaseaemia at diagnosis, and who do not show normalization of liver enzymes after 12 months of gluten-free diet, likely suffer from coexisting liver disease. In such cases, the research team recommends further assessment to assess the possible coexisting liver disease. Spotting and treating coexisting liver disease in celiac patients is important for improving liver function and preventing possible complications. Source: Liver International. 2013;33(7):1128-1131.