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Celiac.com 04/08/2015 - The goal of growth-monitoring programs in children is the early detection of any disorders that affect growth. Celiac disease is under-diagnosed in kids whose symptoms include faltering linear growth, short stature, or poor weight gain. A team of researchers recently set out to develop new evidence-based parameters for screening for growth disorders and to evaluate the performance of these cutoffs among children with celiac disease measured regularly in a nationwide growth screening program. The research team included Antti Saari, MD; Samuli Harju, BM; Outi Mäkitie, MD, PhD; Marja-Terttu Saha, MD, PhD; Leo Dunkel, MD, PhD; and Ulla Sankilampi, MD, PhD. They are variously affiliated with the Department of Pediatrics, School of Medicine, University of Eastern Finland, Kuopio, the Children’s Hospital at the University of Helsinki and Helsinki University Hospital in Helsinki, Finland, the Folkhälsan Research Centre in Helsinki, Finland, the Department of Molecular Medicine and Surgery at the Karolinska Institute in Stockholm, Sweden, the Department of Pediatrics at Tampere University Hospital in Tampere, Finland, the Centre for Endocrinology at the William Harvey Research Institute of Barts and the London School of Medicine and Dentistry at Queen Mary University of London in London, England and the Department of Pediatrics at Kuopio University Hospital, Kuopio, Finland. Their longitudinal retrospective study included growth data of healthy children from primary health care providers, and children with celiac disease from primary health care, and three university hospital outpatient clinics in Finland, Kuopio University Hospital, Tampere University Hospital, and Helsinki University Hospital, from January 1, 1994, to April 9, 2009. Children of the reference population were under 20 years of age, while children in the celiac disease group were between 1 and 16 years of age. In the reference population of 51,332 healthy children, the team screened according to five age- and sex-specific growth parameters: height standard deviation score and body mass index standard deviation score, distance from the population mean, distance from target height, change in height standard deviation score, and change in body mass index standard deviation score. They evaluated these parameters and their combination in 177 children with celiac disease by analyzing longitudinal growth data from birth until diagnosis of celiac disease. They measured the screening accuracy for detecting abnormal growth in children with celiac disease by using receiver operating characteristics analysis expressed as the area under the curve. When the team screened using the combination of all 5 growth-screening parameters, they detected celiac disease with good accuracy ([95% CI] = 0.88 [0.84–0.93] for girls and 0.84 [0.77–0.91] for boys). When they set the screening specificity at 90%, they saw abnormal growth in 57% of the girls with celiac disease, and in 48% of the boys with celiac disease for two years prior to diagnosis. This study shows that most kids with celiac disease experience faltering growth prior to diagnosis. An effective growth-monitoring program could have detected celiac disease in these kids several years earlier. By using several growth-monitoring parameters in combination, preferably using computerized screening algorithms that are integrated into an electronic health record system, researchers can improve sreening accuracy. Source: JAMA Pediatr. 2015;169(3):e1525. doi:10.1001/jamapediatrics.2015.25.
Celiac.com 12/28/2009 - A team of researchers recently set out to compare continual monitoring of intraepithelial lymphocyte immunophenotype and clonality against snapshot analysis in the surveillance of refractory celiac disease. The research team was made up of H. Liu, R. Brais, A. Lavergne-Slove, Q. Jeng, K. Payne K, H. Ye, Z. Liu, J. Carreras, Y. Huang, C. M. Bacon, R. Hamoudi, V. Save, L. Venkatraman, P. G. Isaacson, J. Woodward, and M. Q. Du of Addenbrooke's Hospital, Cambridge, UK. Often, people with refractory celiac disease suffer from abnormal immunophenotype and monoclonality of intraepithelial lymphocytes (IELs). No good studies have been done to compare the utility of continual monitoring of IEL immunophenotype and clonality in monitoring refractory celiac disease (RCD). To address this deficiency, and to gather some data for comparison, the team used CD3e/CD8 double immunohistochemistry and PCR-based clonality analysis of the rearranged TCR genes to evaluate diagnostic and follow-up biopsies from 33 people with proven celiac disease, 7 with suspected refractory celiac disease, 41 with proven refractory celiac disease, and 20 with enteropathy associated T-cell lymphoma (including 11 evolved from RCD). The team found aberrant immunophenotype (CD3epsilon(+)CD8(-) IEL >/=40%) and monoclonality in occasional celiac disease biopsies, either transiently in celiac patients not following a gluten free diet, or in those who later developed refractory celiac disease, suspected RCD, or enteropathy associated T-cell lymphoma (EATL). By comparison, they found aberrant immunophenotype and monoclonality respectively in 30 of 41 (73%) and 24 of 37 (65%) biopsies at the time of diagnosis for refractory celiac disease. Among the patients with refractory celiac disease showed no such abnormalities in their diagnostic biopsies, 8 of 10 (80%) and 5 of 11 (45%) cases showed aberrant immunophenotype and monoclonality respectively upon follow-up. Whether found in initial or follow-up biopsies, the ongoing development of both aberrant immunophenotype and monoclonality is a common facet of refractory celiac disease. One key point was that the presence of both persistent monoclonality and aberrant immunophenotype, especially <>/=>80% CD3epsilon(+)CD8(-) IEL, was a strong predictor of enteropathy associated T-cell lymphoma development in patients with RCD (P=0.001). From these findings, the team found concludes that the continual monitoring of both immunophenotype and clonality of IEL is superior to snapshot analysis for diagnosis and follow-up of refractory celiac disease, and could provide a useful tool for surveillance of patients at risk of developing EATL. Source: Gut. 2009 Dec 8.
Celiac.com 11/03/2008 - Blood testing for radioimmunoassay (RIA) tissue transglutaminase auto-antibodies (tTG-Abs) has proven to be a sensitive test for celiac disease follow-up. Recent studies have shown that RIA can accurately detect tTG-Abs in human saliva. However, not much is known about reliability of this method for monitoring the progress of celiac disease over time in patients who are attempting to follow a gluten-free diet. A team of researchers recently set out to assess salivary RIA tTG-Abs in celiac children on gluten-free diet. The research team included doctors M. Bonamico, R. Nenna, R.P.L. Luparia, C. Perricone, M. Montuori, F. Lucantoni, A. Castronovo, S. Mura; A. Turchetti, P. Strappini, and C. Tiberti. The team evaluated blood and saliva samples taken from 109 children at the time of their diagnosis for celiac disease. The first group included 71 females, with an average age of 9.4 years. A second group included 58 people who were following a gluten-free diet. The second group was broken into two subgroups: group 2a with 36 patients assessed at 3-6 months; and group 2b with 34 patients at 9 months or more (group 2b). The research team also included two control groups matched for age and sex. Group 3 included 89 gastroenterological patients, while group 4 included 49 healthy subjects. The team used RIA to detect tTG-Abs in saliva and blood, and compared the results against two other established tests: serum tTG-Abs ELISA and IgA anti-endomysium antibodies (EMA). The team detected salivary RIA tTG-Abs in 94.5% of patients from group 1, 66.7% of celiac patients from group 2a, and 50.0% from 2b. They detected blood RIA tTG-Abs in 98.2% of patients from group 1, 72.2% of celiac patients from group 2a, and 50.0% from 2b. The longer patients were on a gluten-free diet, the more the tTG-Abs decreased. The research team also found a correlation between saliva and serum levels (r = 0.75, P = 0.0001). A celiac disease follow-up showed comparable salivary and serum RIA sensitivities, and higher levels for EMA and ELISA methods. The research team concluded that it is possible to measure salivary tTG-Abs with a high level of accuracy; both at initial diagnosis for celiac disease, and also while patients are following a gluten-free diet. This discovery means that doctors treating people with celiac disease might soon be able to use a simple saliva test to monitor the progress of their patients’ gluten-free diets. Such a development might take remove much of the guesswork for celiacs who are trying to follow a gluten-free diet, and would be particularly useful for patients who might be asymptomatic, or who are at risk for celiac-associated conditions. Aliment Pharmacol Ther. 2008; 28(3): 364-370.