Gene expression, lipidomic and growth impairment findings suggest that the natural history of celiac disease (CD) starts before the gluten-induced immune response. Gluten intake in the first years of ...life is a controversial risk factor. We aimed to estimate the risk of developing CD associated with the amount of gluten intake and the serum inflammatory profile in genetically predisposed infants. From an Italian cohort of children at risk for CD, we enrolled 27 children who developed CD (cases) and 56 controls matched by sex and age. A dietary interview at 9, 12, 18, 24 and 36 months was performed. Serum cytokines (INFγ, IL1β, IL2, IL4, IL6, IL10 IL12p70, IL17, and TNFα) were analysed at 4 and 36 months. Infants who developed CD by 6 years showed an increase in serum cytokines (INFγ, IL1β, IL2, IL6, IL10, IL12p70 and TNFα) at 4 months of age before gluten introduction. CD cases ate significantly more gluten in the second year of life than controls, and gluten intake in the second year of life was strongly correlated with serum cytokines (INFγ, IL2, IL4, IL12p70, IL17) at 36 months only in CD cases. The dietary pattern of infants who developed CD was characterized by high consumption of biscuits and fruit juices and low intake of milk products, legumes, vegetables and fruits. Genetically predisposed infants who developed CD showed a unique serum cytokine profile at 4 months before gluten consumption. The amount of gluten was strongly correlated with an inflammatory profile in serum cytokines at 36 months only in infants who developed CD.
Can Celiac Disease Be Prevented? Auricchio, Renata; Troncone, Riccardo
Frontiers in immunology,
05/2021, Letnik:
12
Journal Article
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Celiac disease (CD) is an autoimmune disorder triggered by gluten in genetically susceptible individuals characterized by a variable combination of gluten-dependent symptoms, presence of specific ...autoantibodies and enteropathy. The health burden of CD is considerable, as it reduces quality of life and, at a societal level, has extensive negative economic consequences. Prevention strategies are based on the identification of at-risk subjects and identification and elimination of risk factors. A number of prospective observational and interventional studies conducted on the general population, and more often in subjects at-risk, have given important information on the natural history of the disease. Both genetic and environmental factors have been identified with the former, in particular histocompatibility genes, playing a major role. Environmental factors, some operating already before birth, have been identified, with feeding pattern in the first year of life (breast feeding, amount and time of introduction of gluten) and infections being the most relevant. Prospective studies have also allowed the identification of biomarkers predictive of the disease which in perspective could better define the population on which to intervene. Interventions have been so far limited to modifications of feeding patterns. However, as also learnt from diseases that share with CD genetic risk factors and mechanisms of damage, such as type 1 diabetes (T1D), future strategies may be envisaged based on protection from infections, manipulation of microbiota, intervention on T cells.
This guideline presents recommendations for the management of coeliac disease (CD) and other gluten-related disorders both in adults and children. There has been a substantial increase in the ...prevalence of CD over the last 50 years and many patients remain undiagnosed. Diagnostic testing, including serology and biopsy, should be performed on a gluten-containing diet. The diagnosis of CD is based on a combination of clinical, serological and histopathological data. In a group of children the diagnosis may be made without biopsy if strict criteria are available. The treatment for CD is primarily a gluten-free diet (GFD), which requires significant patient education, motivation and follow-up. Slow-responsiveness occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms necessitate a review of the original diagnosis, exclude alternative diagnoses, confirm dietary adherence (dietary review and serology) and follow-up biopsy. In addition, evaluation to exclude complications of CD, such as refractory CD or lymphoma, should be performed. The guideline also deals with other gluten-related disorders, such as dermatitis herpetiformis, which is a cutaneous manifestation of CD characterized by granular IgA deposits in the dermal papillae. The skin lesions clear with gluten withdrawal. Also, less well-defined conditions such as non-coeliac gluten sensitivity (NCGS) and gluten-sensitive neurological manifestations, such as ataxia, have been addressed. Newer therapeutic modalities for CD are being studied in clinical trials but are not yet approved for use in practice.
Pivotal Role of Inflammation in Celiac Disease Barone, Maria Vittoria; Auricchio, Renata; Nanayakkara, Merlin ...
International journal of molecular sciences,
06/2022, Letnik:
23, Številka:
13
Journal Article
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Celiac disease (CD) is an immune-mediated enteropathy triggered in genetically susceptible individuals by gluten-containing cereals. A central role in the pathogenesis of CD is played by the ...HLA-restricted gliadin-specific intestinal T cell response generated in a pro-inflammatory environment. The mechanisms that generate this pro-inflammatory environment in CD is now starting to be addressed. In vitro study on CD cells and organoids, shows that constant low-grade inflammation is present also in the absence of gluten. In vivo studies on a population at risk, show before the onset of the disease and before the introduction of gluten in the diet, cellular and metabolic alterations in the absence of a T cell-mediated response. Gluten exacerbates these constitutive alterations in vitro and in vivo. Inflammation, may have a main role in CD, adding this disease tout court to the big family of chronic inflammatory diseases. Nutrients can have pro-inflammatory or anti-inflammatory effects, also mediated by intestinal microbiota. The intestine function as a crossroad for the control of inflammation both locally and at distance. The aim of this review is to discuss the recent literature on the main role of inflammation in the natural history of CD, supported by cellular fragility with increased sensitivity to gluten and other pro-inflammatory agents.
Celiac disease (CD) is a chronic inflammatory disease caused by a genetic predisposition to an abnormal T cell-mediated immune response to the gluten in the diet. Different environmental ...proinflammatory factors can influence and amplify the T cell-mediated response to gluten. The aim of this manuscript was to study the role of enterocytes in CD intestinal inflammation and their response to different proinflammatory factors, such as gliadin and viruses. Intestinal biopsies from CD patients on a gluten-containing (GCD-CD) or a gluten-free diet (GFD-CD) as well as biopsies from potential CD patients (Pot-CD) before the onset of intestinal lesions and controls (CTR) were used to investigate IL-1β and IL-6 mRNA levels in situ. Organoids from CD patients were used to test the levels of NF-κB, ERK, IL-6, and IL-1β by Western blot (WB), ELISA, and quantitative PCR. The Toll-like receptor ligand loxoribine (Lox) and gliadin peptide P31-43 were used as proinflammatory stimuli. In CD biopsies inflammation markers IL-1β and IL-6 were increased in the enterocytes, and also in Pot-CD before the onset of the intestinal lesion and in GFD-CD. The inflammatory markers pNF-κB, pERK, IL-1β, and IL-6 were increased and persistent in CD organoids; these organoids were more sensitive to P31-43 and Lox stimuli compared with CTR organoids. Taken together, these observations point to constitutive inflammation in CD enterocytes, which are more sensitive to inflammatory stimuli such as food components and viruses.
Potential celiac disease (PCD) is a clinical condition characterised by the presence of a positive CD-specific serology and a normal intestinal architecture. Asymptomatic PCD patients are generally ...advised to continue on a gluten-containing diet (GCD), but long-term risks of this approach have never been explored. In the present study, we aimed to investigate nutritional and autoimmune complications possibly developing overtime in a cohort of asymptomatic PCD children on a GCD. We compared children’s parameters of growth, nutritional status, and autoimmunity between the time of diagnosis and on the occasion of their last medical check, after a long-term gluten-containing diet. Altogether, we collected data from 171 PCD children with a mean follow-up time of 3 years (range 0.35–15.3 years). During follow-up, although patients did not reduce their amount of daily gluten intake, their anti-tissue transglutaminase (anti-TG2) antibodies spontaneously and significantly decreased. Most parameters analysed had not changed during follow-up (height centile, ferritin, albumin, cholesterol, calcium, alkaline phosphatase, parathormone, and vitamin D) or even improved significantly (weight and BMI centile, haemoglobin, blood iron, HDL, glycaemia, and HbA1C, p < 0.05), always remaining within the limit of normality. Equally, autoantibodies for other concomitant autoimmune disorders did not increase overtime. Similar results were obtained excluding from analysis patients who had stopped producing anti-TG2 and those with a follow-up time < 3 years. Our pilot study has provided reassuring results regarding the maintenance of a gluten-containing diet in asymptomatic PCD children, even when long-term follow-up was considered.
Celiac disease (CD) is a systemic autoimmune disease due to a dysregulated mucosal immune response to gluten and related prolamines in genetically predisposed individuals. It is a common disorder ...affecting ~1% of the general population, its incidence is steadily increasing. Changes in the clinical presentation have become evident since the 80s with the recognition of extra-intestinal symptoms like short stature, iron deficiency anemia, altered bone metabolism, elevation of liver enzymes, neurological problems. Recent studies have shown that the overall prevalence of extra-intestinal manifestations is similar between pediatric and adult population; however, the prevalence of specific manifestations and rate of improvement differ in the two age groups. For instance, clinical response in children occurs much faster than in adults. Moreover, an early diagnosis is decisive for a better prognosis. The pathogenesis of extra-intestinal manifestations has not been fully elucidated yet. Two main mechanisms have been advanced: the first related to the malabsorption consequent to mucosal damage, the latter associated with a sustained autoimmune response. Importantly, since extra-intestinal manifestations dominate the clinical presentation of over half of patients, a careful case-finding strategy, together with a more liberal use of serological tools, is crucial to improve the detection rate of CD.
Assessment of adherence to gluten-free diet (GFD) represents the cornerstone in the management of coeliac disease. The primary aim of this study was to assess diet adherence through a questionnaire ...adapted to children. The secondary aim was to identify influencing factors and outcomes related to diet adherence. In this study, data about diagnosis, education, quality of life (QoL) and anti-transglutaminase (anti-TG2) titers of 160 coeliac children were collected. For the assessment of diet adherence, all participants completed the questionnaire modified from Leffler et al. (2009), while a random sample of 37 also underwent an extensive dietary interview. According to the questionnaire, diet adherence was excellent in 95 (59.4%), fair in 46 (28.8%) and low in 19 (11.9%) patients. Children diagnosed with biopsy showed better adherence than those with a biopsy-sparing approach (
0.036). Adherence to GFD tended to worsen during the follow up, with the average length of follow up being associated with lower scores of diet adherence (
0.009). Moreover, adherence to GFD decreased throughout school career, dropping from elementary until high school (
0.037). A positive correlation was observed between adherence to GFD and growth percentiles, which increased when higher scores of adherence were achieved. Diet adherence positively correlated with QoL (
0.001). In conclusion, the questionnaire displayed good sensitivity in detecting problems in diet adherence, being useful as a screening tool. Better comprehension of influencing factors and outcomes may allow the development of new strategies to improve diet adherence.
Objectives: Coeliac disease is a multifactorial disorder influenced by environmental, genetic and immunological factors. Interleukin (IL)-21 has been linked to an increase disease risk and the serum ...level of IL-21 seems to be increased in CD compared to a healthy control population.
Methods: Sera were collected from 160 CD patients, 120 untreated and 40 following a gluten-free diet, and form 45 healthy subjects. Serum IL-21 was evaluated by specific ELISA tests.
Results: Our data show that patients with untreated CD display IL-21 concentrations significantly higher than both treated-CD patients (following a gluten-free diet) and controls. In addition, serum IL-21 correlates with serum titres of anti-tTG IgA autoantibodies. Finally, our results show a correlation of this cytokine with duodenal mucosal damage.
Conclusions: A role of gluten, as antigen with stimulatory function on IL-21 production, seems to be confirmed by the longitudinal analyses showing that the gluten-free diet decreases to a nearly undetectable amount this cytokine. In addition, the finding of a positive correlation between the serum amount of IL-21 and the grade of duodenal mucosa damage suggests a strong immunomodulatory effect of this cytokine on cytotoxic T lymphocyte functions. This study provides an extra evidence to emerging data on the potential role IL-21 in CD pathogenesis, suggesting its involvement in the development and progression of CD.
Significance statement: In untreated CD, serum IL-21 shows higher levels compared with treated CD and healthy subjects. Serum amounts of IL-21 correlate with anti-tTG IgA autoantibodies and with duodenal mucosa damage.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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