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1.
Quantification of Accidental Gluten Contamination in the Diet of Children with Treated Celiac Disease.
Monachesi, C, Verma, AK, Catassi, GN, Galeazzi, T, Franceschini, E, Perticaroli, V, Lionetti, E, Catassi, C
Nutrients. 2021;(1)
Abstract
A strict gluten-free diet is extremely difficult to maintain. Protracted ingestion of gluten traces (>10 mg/day) is sufficient to cause significant damage in the architecture of the small intestinal mucosa in patients on treatment for celiac disease. The aim of this study was to directly measure the level of contaminating gluten in the daily diet of celiac children following a gluten-free diet. From April 2019 to December 2019, celiac disease children (2-18 years old) on a gluten-free diet for ≥6 months were offered to participate in this prospective-observational study. Patients and their caregivers were invited to provide a representative portion (about 10 g) of all meals consumed during a 24-h period. Participants were requested to weigh all ingested food and report items in a 24-h food diary. The gluten content was quantified by the R5 sandwich enzyme-linked immunosorbent assay method. Sixty-nine children completed the protocol. Overall, 12/448 (2.7%) food samples contained detectable amounts of gluten; of them, 11 contained 5-20 ppm and 1 >20 ppm. The 12 contaminated food samples belonged to 5/69 enrolled patients. In these 5 children, the daily gluten intake was well below the safety threshold of 10 mg/day. The present findings suggest that in a country characterized by high celiac disease awareness, the daily unintended exposure to gluten of treated celiac children on regular follow-up is very low; reassuringly, the presence of gluten traces did not lead to exceed the tolerable threshold of 10 mg/day of gluten intake in the gluten-free diet.
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2.
Poor Sensitivity of Fecal Gluten Immunogenic Peptides and Serum Antibodies to Detect Duodenal Mucosal Damage in Celiac Disease Monitoring.
Laserna-Mendieta, EJ, Casanova, MJ, Arias, Á, Arias-González, L, Majano, P, Mate, LA, Gordillo-Vélez, CH, Jiménez, M, Angueira, T, Tébar-Romero, E, et al
Nutrients. 2020;(1)
Abstract
A lifelong gluten-free diet (GFD) is the only current treatment for celiac disease (CD), but strict compliance is complicated. Duodenal biopsies are the "gold standard" method for diagnosing CD, but they are not generally recommended for disease monitoring. We evaluated the sensitivity and specificity of fecal gluten immunogenic peptides (GIPs) to detect duodenal lesions in CD patients on a GFD and compared them with serum anti-tissue transglutaminase (tTG) IgA antibodies. A prospective study was conducted at two tertiary centers in Spain on a consecutive series of adolescents and adults with CD who maintained a long-lasting GFD. Adherence to a GFD and health-related quality of life were scored with validated questionnaires. Mucosal damage graded according to the Marsh-Oberhüber classification (Marsh 1/2/3) was used as the reference standard. Of the 97 patients included, 27 presented duodenal mucosal damage and 70 had normal biopsies (Marsh 0). The sensitivity (33%) and specificity (81%) of GIPs were similar to those provided by the two assays used to measure anti-tTG antibodies. Scores in questionnaires showed no association with GIP, but an association between GIPs and patients' self-reported gluten consumption was found (p = 0.003). GIP displayed low sensitivity but acceptable specificity for the detection of mucosal damage in CD.
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3.
Remission of Pituitary Autoimmunity Induced by Gluten-Free Diet in Patients With Celiac Disease.
Bellastella, G, Maiorino, MI, Cirillo, P, Longo, M, Pernice, V, Costantino, A, Annunziata, C, Bellastella, A, Esposito, K, De Bellis, A
The Journal of clinical endocrinology and metabolism. 2020;(7)
Abstract
CONTEXT An improvement of some autoimmune diseases associated with celiac disease (CD) has been observed after a gluten-free diet (GFD). OBJECTIVE The aim of this longitudinal study was to evaluate the effect of a GFD on autoimmune pituitary impairment in patients with CD and potential/subclinical lymphocytic hypophysitis (LYH). DESIGN Five-year longitudinal observational study. SETTING Tertiary referral center for immunoendocrinology at the University of Campania "Luigi Vanvitelli". PATIENTS Ninety-three newly diagnosed LYH patients (high titer of antipituitary antibodies [APA] and normal or subclinically impaired pituitary function) were enrolled from 2000 to 2013 and grouped as follows: group 1, consisting of 43 patients with LYH + CD, and group 2, consisting of 50 patients with isolated LYH only. INTERVENTION A GFD was started in patients in group 1 after the diagnosis of CD. MAIN OUTCOME MEASURES APA titers and pituitary function were evaluated at the beginning of the study and then yearly for 5 years in both groups. Patients progressing to a clinically overt LYH were excluded from the follow-up. RESULTS Complete remission of LYH (disappearance of APA and recovery of pituitary function in patients with previous subclinical hypopituitarism) occurred in 15 patients in group 1 after a GFD (34%) and spontaneously in only 1 patient in group 2 (2%) (P < .001). Two patients in group 1 and 25 in group 2 progressed to a clinically overt hypopituitarism and dropped out from the study to receive an appropriate replacement therapy. The presence of CD was the only independent predictor of pituitary function recovery (hazard ratio [HR] 0.059, 95% confidence interval [CI] 0.01-0.54, P = .012). CONCLUSION In patients with LYH and CD, a GFD may be able to induce remission of subclinical LYH, or prevent the progression to clinical stage of this disease.
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4.
Role of capsule endoscopy in suspected celiac disease: A European multi-centre study.
Luján-Sanchis, M, Pérez-Cuadrado-Robles, E, García-Lledó, J, Juanmartiñena Fernández, JF, Elli, L, Jiménez-García, VA, Egea-Valenzuela, J, Valle-Muñoz, J, Carretero-Ribón, C, Fernández-Urién-Sainz, I, et al
World journal of gastroenterology. 2017;(4):703-711
Abstract
AIM: To analyze the diagnostic yield (DY), therapeutic impact (TI) and safety of capsule endoscopy (CE). METHODS This is a multi-centre, observational, analytical, retrospective study. A total of 163 patients with suspicion of celiac disease (CD) (mean age = 46.4 ± 17.3 years, 68.1% women) who underwent CE from 2003 to 2015 were included. Patients were divided into four groups: seronegative CD with atrophy (Group-I, n = 19), seropositive CD without atrophy (Group-II, n = 39), contraindication to gastroscopy (Group-III, n = 6), seronegative CD without atrophy, but with a compatible context (Group-IV, n = 99). DY, TI and the safety of CE were analysed. RESULTS The overall DY was 54% and the final diagnosis was villous atrophy (n = 65, 39.9%), complicated CD (n = 12, 7.4%) and other enteropathies (n = 11, 6.8%; 8 Crohn's). DY for groups I to IV was 73.7%, 69.2%, 50% and 44.4%, respectively. Atrophy was located in duodenum in 24 cases (36.9%), diffuse in 19 (29.2%), jejunal in 11 (16.9%), and patchy in 10 cases (15.4%). Factors associated with a greater DY were positive serology (68.3% vs 49.2%, P = 0.034) and older age (P = 0.008). On the other hand, neither sex nor clinical presentation, family background, positive histology or HLA status were associated with DY. CE results changed the therapeutic approach in 71.8% of the cases. Atrophy was associated with a greater TI (92.3% vs 45.3%, P < 0.001) and 81.9% of the patients responded to diet. There was one case of capsule retention (0.6%). Agreement between CE findings and subsequent histology was 100% for diagnosing normal/other conditions, 70% for suspected CD and 50% for complicated CD. CONCLUSION CE has a high DY in cases of suspicion of CD and it leads to changes in the clinical course of the disease. CE is safe procedure with a high degree of concordance with histology and it helps in the differential diagnosis of CD.
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5.
Exploring the risk factors for differences in the cumulative incidence of coeliac disease in two neighboring countries: the prospective DIABIMMUNE study.
Simre, K, Uibo, O, Peet, A, Tillmann, V, Kool, P, Hämäläinen, AM, Härkönen, T, Siljander, H, Virtanen, S, Ilonen, J, et al
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2016;(11):1296-1301
Abstract
BACKGROUND During the last several decades the prevalence of coeliac disease (CD) has increased worldwide. AIM: To compare the cumulative incidence of CD between Estonian and Finnish children and to identify the risk factors. MATERIALS AND METHODS Children were recruited as part of the DIABIMMUNE Study. In the birth cohort (BC) 258 children from Estonia and 305 from Finland, and in the young children's cohort (YCC) 1363 and 1384 children were followed up, respectively. The diagnosis of CD was made in accordance with the ESPGHAN guidelines-the presence of IgA-tTG antibodies and small bowel villous atrophy. RESULTS During the study period 29 children developed CD. The cumulative incidence of CD was significantly higher in Finland (0.77% vs 0.27%; P=0.01). No difference was seen between the children with CD and the controls in the duration of breastfeeding or the age at cereal introduction. The BC children with CD had had significantly more episodes of infections with fever by the age of 12 months compared to the controls (3.4 vs 1.4; P=0.04). CONCLUSION The 5-year cumulative incidence of childhood CD is significantly higher in Finland than in Estonia. Sequential infections early in life may increase the risk for developing CD.
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6.
Patients with mild enteropathy have apoptotic injury of enterocytes similar to that in advanced enteropathy in celiac disease.
Das, P, Gahlot, GP, Mehta, R, Makharia, A, Verma, AK, Sreenivas, V, Panda, SK, Ahuja, V, Gupta, SD, Makharia, GK
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2016;(11):1290-1295
Abstract
BACKGROUND Severity of villous atrophy in celiac disease (CeD) is the cumulative effect of enterocyte loss and cell regeneration. Gluten-free diet has been shown to benefit even in patients having a positive anti-tissue transglutaminase (tTG) antibody titre and mild enteropathy. AIM: We explored the balance between mucosal apoptotic enterocyte loss and cell regeneration in mild and advanced enteropathies. METHODS Duodenal biopsies from patients with mild enteropathy (Marsh grade 0 and 1) (n=26), advanced enteropathy (Marsh grade ≥2) (n=41) and control biopsies (n=12) were subjected to immunohistochemical staining for end-apoptotic markers (M30, H2AX); markers of cell death (perforin, annexin V); and cell proliferation (Ki67). Composite H-scores based on the intensity and distribution of markers were compared. RESULTS End-apoptotic markers and marker of cell death (perforin) were significantly up-regulated in both mild and advanced enteropathies, in comparison to controls; without any difference between mild and advanced enteropathies. Ki67 labelling index was significantly higher in crypts of mild enteropathy, in comparison to controls, suggesting maintained regenerative activity in the former. CONCLUSIONS Even in patients with mild enteropathy, the rate of apoptosis is similar to those with advanced enteropathy. These findings suggest the necessity of reviewing the existing practice of not treating patients with mild enteropathy.
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7.
Transcultural adaptation and validation of the Celiac Dietary Adherence Test. A simple questionnaire to measure adherence to a gluten-free diet.
Fueyo-Díaz, R, Gascón-Santos, S, Asensio-Martínez, Á, Sánchez-Calavera, MA, Magallón-Botaya, R
Revista espanola de enfermedades digestivas. 2016;(3):138-44
Abstract
BACKGROUND AND AIMS A gluten-free diet is to date the only treatment available to celiac disease sufferers. However, systematic reviews indicate that, depending on the method of evaluation used, only 42% to 91% of patients adhere to the diet strictly. Transculturally adapted tools that evaluate adherence beyond simple self-informed questions or invasive analyses are, therefore, of importance. The aim is to obtain a Spanish transcultural adaption and validation of Leffler's Celiac Dietary Adherence Test. METHODS A two-stage observational transversal study: translation and back translation by four qualified translators followed by a validation stage in which the questionnaire was administered to 306 celiac disease patients aged between 12 and 72 years and resident in Aragon. Factorial structure, criteria validity and internal consistency were evaluated. RESULTS The Spanish version maintained the 7 items in a 3-factor structure. Reliability was very high in all the questions answered and the floor and ceiling effects were very low (4.3% and 1%, respectively). The Spearman correlation with the self-efficacy and life quality scales and the self-informed question were statistically significant (p < 0.01). According to the questionnaire criteria, adherence was 72.3%. CONCLUSION The Spanish version of the Celiac Dietary Adherence Test shows appropriate psychometric properties and is, therefore, suitable for studying adherence to a gluten-free diet in clinical and research environments.
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8.
High rate of spontaneous normalization of celiac serology in a cohort of 446 children with type 1 diabetes: a prospective study.
Castellaneta, S, Piccinno, E, Oliva, M, Cristofori, F, Vendemiale, M, Ortolani, F, Papadia, F, Catassi, C, Cavallo, L, Francavilla, R
Diabetes care. 2015;(5):760-6
Abstract
OBJECTIVE In children with type 1 diabetes mellitus (T1DM), elevated levels of antitissue transglutaminase (anti-tTG) antibody may spontaneously normalize, despite continued consumption of gluten. We aimed to investigate the prevalence of spontaneous normalization of anti-tTG levels and the existence of factors predictive for this outcome. RESEARCH DESIGN AND METHODS All children referred from 2002 to 2012 were screened for celiac disease (CD) at diabetes onset and at specific intervals. In the presence of a high anti-tTG titer or clinical symptoms, children were offered endoscopy, and asymptomatic patients with a low anti-tTG titer were invited to a second serological test after 6 months of eating a gluten-containing diet. RESULTS The study included 446 children. Of these, 65 (14.5%) became positive for celiac serology: 38 (58%) had a persistently elevated anti-tTG titer and 27 (41%) fluctuating anti-tTG titer; 18 (28%) became negative. The prevalence of positive CD autoimmunity and overt CD was 14.3% (95% CI 11-17) and 8.5% (95% CI 5-10), 15- and 8-times higher than the general pediatric population, respectively. Asymptomatic children older than 9.1 years at T1DM onset had the lowest risk to develop CD. CONCLUSIONS Serum anti-tTG levels decreased spontaneously in 40% of children with T1DM and became negative in 20%, despite gluten consumption. This finding supports the hypothesis of a state of temporary positivity of celiac serology in children with diabetes. In absence of clinical symptoms or signs of CD, histological confirmation of the disease and the gluten-free diet should be postponed to avoid unnecessary procedures and reduce an additional psychological burden.
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9.
B-vitamin status in relation to bone mineral density in treated celiac disease patients.
Clarke, M, Ward, M, Dickey, W, Hoey, L, Molloy, AM, Waldron, L, Varghese, A, McCann, A, Blayney, JK, McNulty, H
Scandinavian journal of gastroenterology. 2015;(8):975-84
Abstract
OBJECTIVES Patients with celiac disease (CD) are at increased risk of osteoporosis and compromised B-vitamin status. Emerging evidence supports a beneficial role of folate and the metabolically related B-vitamins in bone health in generally healthy adults, but no previous study has investigated this in CD patients. The aim of the current study was to examine the relationship of folate, vitamins B12, B6 and B2 (riboflavin), and the related metabolite homocysteine, with bone mineral density (BMD) in CD patients. MATERIALS AND METHODS Of the 400 treated adult CD patients invited to participate, 110 responded and met the eligibility criteria for study participation. BMD was measured using dual energy X-ray absorptiometry scanning at the lumbar spine (L1-L4), femoral neck, and total hip sites. Biomarker status of the relevant B-vitamins and homocysteine, and dietary B-vitamin intakes, were measured. RESULTS The significant predictors of low BMD were increasing age (B = 0.080, p < 0.001) and decreasing weight (B = 0.072, p = 0.004), whereas no significant relationship with serum 25-hydroxyvitamin D (B = 0.093, p = 0.928) was observed. Following adjustment for these predictors, serum vitamin B12 (but no other B-vitamin biomarker) was found to be a significant determinant of BMD at the femoral neck (β = 0.416, p = 0.011) and total hip (β = 0.327, p = 0.049) in men only. No significant relationships were found between any of the B-vitamin biomarkers investigated and BMD (at any measured site) in women. CONCLUSION These findings add to current evidence suggesting a potential role of vitamin B12 in BMD, particularly in men, and show such a relationship for the first time in CD patients.
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10.
Advanced glycation end products (AGEs) and the soluble receptor for AGE (sRAGE) in patients with type 1 diabetes and coeliac disease.
Bakker, SF, Tushuizen, ME, Gözütok, E, Çiftci, A, Gelderman, KA, Mulder, CJ, Simsek, S
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2015;(2):230-5
Abstract
BACKGROUND AND AIMS Advanced glycation end (AGE) products play a role in the progression of diabetic complications. Gluten-free diet (GFD) might affect AGE levels in patients who adhere to a GFD because of coeliac disease (CD). The aim of our study was to compare skin AGE levels and soluble receptor AGE levels (sRAGE) in patients with type 1 diabetes (T1DM) with (T1DM + CD) and without CD (T1DM - CD) and healthy controls. METHODS AND RESULTS We recruited 25 T1DM + CD and 25 T1DM - CD patients, matched for age, gender, diabetes duration, and glycaemic control alongside 25 healthy controls. We collected demographic, clinical and biochemical characteristics, including skin autofluorescence (AF), sRAGE and hs-CRP levels. The duration of T1DM in patients was 30 ± 14 (+CD) and 29 ± 14 years (-CD), whereas CD duration in T1DM + CD patients was 14 ± 10 years. Skin AF levels in T1DM patients were higher compared to healthy controls (2.5 ± 0.6 versus 1.9 ± 0.4, p < 0.01) and skin AF was independently associated with age (r = 0.72, p < 0.01). sRAGE levels were higher in T1DM - CD patients compared to healthy controls (1554 ± 449 versus 1309 ± 400, p = 0.049) and independently associated with creatinine levels (r = 0.32, p < 0.01). CONCLUSION Our study demonstrates that skin AGE and sRAGE levels are elevated in T1DM patients compared with healthy controls. No difference in skin AF or sRAGE levels between T1DM patients with or without CD were observed. The present study suggests that differences in microvascular complications between T1DM and T1DM + CD patients are not due to differences in skin AF or sRAGE levels.