-
1.
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.
-
2.
Comparison of DNA methylation profiles from saliva in Coeliac disease and non-coeliac disease individuals.
Hearn, NL, Chiu, CL, Lind, JM
BMC medical genomics. 2020;(1):16
Abstract
BACKGROUND Coeliac disease (CD) is a autoimmune disease characterised by mucosal inflammation in the small intestine in response to dietary gluten. Genetic factors play a key role with CD individuals carrying either the HLA-DQ2 or HLA-DQ8 haplotype, however these haplotypes are present in half the general population making them necessary but insufficient to cause CD. Epigenetic modifications, including DNA methylation that can change in response to environmental exposure could help to explain how interactions between genes and environmental factors combine to trigger disease development. Identifying changes in DNA methylation profiles in individuals with CD could help discover novel genomic regions involved in the onset and development of CD. METHODS The Illumina InfiniumMethylation450 Beadchip array (HM450) was used to compare DNA methylation profiles in saliva, in CD and non-CD affected individuals. CD individuals who had been diagnosed at least 2 years previously; were on a GFD; and who were currently asymptomatic; were compared to age and sex-matched non-CD affected healthy controls. Bisulphite pyrosequencing was used to validate regions found to be differentially methylated. These regions were also validated in a second larger cohort of CD and non-CD affected individuals. RESULTS Methylation differences within the HLA region at HLA-DQB1 were identified on HM450 but could not be confirmed with pyrosequencing. Significant methylation differences near the SLC17A3 gene were confirmed on pyrosequencing in the initial pilot cohort. Interestingly pyrosequencing sequencing of these same sites within a second cohort of CD and non-CD affected controls produced significant methylation differences in the opposite direction. CONCLUSION Altered DNA methylation profiles appear to be present in saliva in CD individuals. Further work to confirm whether these differences are truly associated with CD is needed.
-
3.
The Epidemiology of Celiac Disease in the General Population and High-Risk Groups in Arab Countries: A Systematic Review.
El-Metwally, A, Toivola, P, AlAhmary, K, Bahkali, S, AlKhathaami, A, AlSaqabi, MK, Al Ammar, SA, Jawed, M, Alosaimi, SM
BioMed research international. 2020;:6865917
Abstract
BACKGROUND AND AIMS Celiac disease (CD) is possibly the most common autoimmune disorder, which may lead to dietary problems in the Arab region. This paper is aimed at exploring the epidemiology of the celiac disease in Arab countries, including its prevalence, associated risk factors, and clinical patterns. METHODS An extensive search of the literature was conducted from electronic databases such as PubMed, Embase, and Google Scholar. In total, 134 research papers were retrieved. We extracted studies published from January 1996 to December 2019. Our search was limited to studies published in English. Findings. The review included 35 studies with 22,340 participants from 12 countries and demonstrated a wide variation in the prevalence of CD. The highest prevalence among the general population (3.2%) was reported in Saudi Arabia, and the lowest (0.1%) was reported in Tunisia. Women demonstrated a higher prevalence of celiac disease relative to men. The peak age at diagnosis fell between 1 and 3 years and 9-10 years. Most studies focused on type 1 diabetes. Children with type 1 diabetes have a higher prevalence of CD (range from 5.5% to 20%), while the prevalence of CD in Down's syndrome patients was 1.1% and 10.7% in UAE and Saudi Arabia, respectively. Other autoimmune diseases associated with CD are thyroid disease and irritable bowel disease. The most widely recognized clinical presentation was an inability to flourish and poor weight gain, followed by short stature, abdominal pain, abdominal distension, bloating, and chronic diarrhea. CONCLUSION The prevalence of the celiac disease in Arab countries varies with sex and age. However, we found that celiac disease presented similar clinical characteristics independent of the geographic region. Longitudinal population-based studies are needed to better identify the true burden and determinants of celiac disease.
-
4.
Effect of Gluten-Free Diet on Gut Microbiota Composition in Patients with Celiac Disease and Non-Celiac Gluten/Wheat Sensitivity.
Caio, G, Lungaro, L, Segata, N, Guarino, M, Zoli, G, Volta, U, De Giorgio, R
Nutrients. 2020;(6)
Abstract
Celiac disease (CD) and non-celiac gluten/wheat sensitivity (NCG/WS) are the two most frequent conditions belonging to gluten-related disorders (GRDs). Both these diseases are triggered and worsened by gluten proteins ingestion, although other components, such as amylase/trypsin inhibitors (ATI) and fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), seem to be involved in the NCG/WS onset. Therefore, the only effective treatment to date is the long-life adherence to a strictly gluten-free diet. Recently, increasing attention has been paid to the intestinal barrier, a dynamic system comprising various components, which regulate the delicate crosstalk between metabolic, motor, neuroendocrine and immunological functions. Among the elements characterizing the intestinal barrier, the microbiota plays a key role, modulating the gut integrity maintenance, the immune response and the inflammation process, linked to the CD and NCG/WS outbreak. This narrative review addresses the most recent findings on the gut microbiota modulation induced by the gluten-free diet (GFD) in healthy, CD and NCG/WS patients.
-
5.
Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders.
Barbaro, MR, Cremon, C, Wrona, D, Fuschi, D, Marasco, G, Stanghellini, V, Barbara, G
Nutrients. 2020;(12)
Abstract
Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut-brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut-brain interaction.
-
6.
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.
-
7.
Body composition in children with chronic inflammatory diseases: A systematic review.
Houttu, N, Kalliomäki, M, Grönlund, MM, Niinikoski, H, Nermes, M, Laitinen, K
Clinical nutrition (Edinburgh, Scotland). 2020;(9):2647-2662
Abstract
BACKGROUND & AIMS Aberrations in body composition are expected in children suffering from chronic inflammatory conditions. The objective is to examine whether children with inflammatory bowel disease (IBD: Crohn's disease and ulcerative colitis), coeliac disease, asthma and juvenile idiopathic arthritis (JIA) have an altered body composition as compared to healthy children. METHODS A systematic review, registered in Prospero (registration number: CRD42018107645), was conducted according to PRISMA guidelines. We conducted a search of three databases, Pubmed, Cochrane and Scopus. An assessment of the quality of the study was performed. RESULTS Data from 50 studies, 32 with IBD, 8 with coeliac disease, 2 with asthma and 8 with JIA, involving 2399 children were selected for review after applying the eligibility criteria. In all but 4 studies, children with Crohn's disease exhibited decreased amounts of fat mass and fat free mass. Reductions in fat mass were also evident in studies in children with coeliac disease. It is uncertain whether body composition is altered in children with asthma or JIA. CONCLUSIONS Children with Crohn's disease manifest with lowered adiposity and lean mass and therefore are likely to be at risk for suffering malnutrition-related clinical complications. Apart from Crohn's disease, data examining body composition in children with chronic inflammatory conditions are scarce and there is a paucity of reports examining the relationship between inflammation and body composition. Interpretation of the current study results is hampered by the low quality of the studies and due to the fact that the analyses have been habitually secondary outcomes.
-
8.
Suppressive Mechanisms Induced by Tregs in Celiac Disease.
Asri, N, Rostami-Nejad, M, Barzegar, M, Nikzamir, A, Rezaei-Tavirani, M, Razzaghi, M, Zali, MR
Iranian biomedical journal. 2020;(3):140-7
Abstract
Celiac disease (CD) is a systemic immune-mediated disorder caused by the dietary gluten in individuals who are genetically susceptible to the disease. In fact, CD is a T cell-mediated immune disease in which gluten-derived peptides activate the lamina propria CD4+ Teff cells, and these T-cell subsets can cause the intestinal tissue damages. Also, there are additional subsets of CD4+ T cells with suppressor functions. These subsets express the master transcription factor, FOXP3, and include Tr1 cells and CD4+CD25+ regulatory T cells (Tregs), which are the main population involved in maintaining the peripheral tolerance, preventing the autoimmune diseases and limiting the chronic inflammatory diseases such as CD. The suppressive function of Tregs is important to maintain the immune homeostasis. This paper examined the features and the basic mechanisms used by Tregs to mediate the suppression in CD.
-
9.
Management of Small Bowel Villous Atrophy in Patients Seronegative for Celiac Disease.
Jansson-Knodell, CL, Murray, JA, Rubio-Tapia, A
The American journal of gastroenterology. 2020;(4):492-497
-
10.
Microbial transglutaminase: A biotechnological tool to manage gluten intolerance.
Luongo, D, Maurano, F, Bergamo, P, Rossi, M
Analytical biochemistry. 2020;:113584
Abstract
Celiac disease (CD) is a chronic immune-mediated disease in which gluten ingestion leads to damage of the small intestinal mucosa in genetically susceptible individuals. The enteropathy is mainly induced by the production of IFN-γ from intestinal CD4+T cells that recognise gliadin peptides following deamidation by tissue transglutaminase. The only available therapy is a strict, lifelong gluten-free diet (GFD). This diet is strongly demanding for patients, which justifies the search for alternative strategies. The enzyme approach is one promising strategy to address this issue. In particular, transamidation of wheat gliadin by microbial transglutaminase (mTG) was fully effective at inhibiting gliadin-specific IFN-γ secretion in intestinal T cells from CD patients. Furthermore, transamidated gliadin induced higher levels of the anti-inflammatory IL-10 than native gliadin in different in vitro models. These data suggest that a more balanced immune response could be induced by mTG-treated gliadin in the small intestine of celiac patients. Furthermore, the highlighted biological property of mTG-treated gliadin could be exploited to induce tolerance to native gliadin in at-risk individuals.