Medicine Gastroenterology

Celiac Disease Research and Management

Description

This cluster of papers focuses on the diagnosis, management, prevalence, genetic variants, autoimmune diseases, intestinal permeability, histopathology, and nutritional deficiencies related to celiac disease and gluten sensitivity.

Keywords

Celiac Disease; Gluten Sensitivity; Diagnosis; Management; Prevalence; Genetic Variants; Autoimmune Diseases; Intestinal Permeability; Histopathology; Nutritional Deficiencies

Celiac Sprue, a widely prevalent autoimmune disease of the small intestine, is induced in genetically susceptible individuals by exposure to dietary gluten. A 33-mer peptide was identified that has several … Celiac Sprue, a widely prevalent autoimmune disease of the small intestine, is induced in genetically susceptible individuals by exposure to dietary gluten. A 33-mer peptide was identified that has several characteristics suggesting it is the primary initiator of the inflammatory response to gluten in Celiac Sprue patients. In vitro and in vivo studies in rats and humans demonstrated that it is stable toward breakdown by all gastric, pancreatic, and intestinal brush-border membrane proteases. The peptide reacted with tissue transglutaminase, the major autoantigen in Celiac Sprue, with substantially greater selectivity than known natural substrates of this extracellular enzyme. It was a potent inducer of gut-derived human T cell lines from 14 of 14 Celiac Sprue patients. Homologs of this peptide were found in all food grains that are toxic to Celiac Sprue patients but are absent from all nontoxic food grains. The peptide could be detoxified in in vitro and in vivo assays by exposure to a bacterial prolyl endopeptidase, suggesting a strategy for oral peptidase supplement therapy for Celiac Sprue.
The number of coeliac disease diagnoses has increased in the recent past and according to screening studies, the total prevalence of the disorder is around 1%.To establish whether the increased … The number of coeliac disease diagnoses has increased in the recent past and according to screening studies, the total prevalence of the disorder is around 1%.To establish whether the increased number of coeliac disease cases reflects a true rise in disease frequency.The total prevalence of coeliac disease was determined in two population-based samples representing the Finnish adult population in 1978-80 and 2000-01 and comprising 8000 and 8028 individuals, respectively. Both clinically-diagnosed coeliac disease patients and previously unrecognized cases identified by serum endomysial antibodies were taken into account.Only two (clinical prevalence of 0.03%) patients had been diagnosed on clinical grounds in 1978-80, in contrast to 32 (0.52%) in 2000-01. The prevalence of earlier unrecognized cases increased statistically significantly from 1.03% to 1.47% during the same period. This yields a total prevalence of coeliac disease of 1.05% in 1978-80 and 1.99% in 2000-01.The total prevalence of coeliac disease seems to have doubled in Finland during the last two decades, and the increase cannot be attributed to the better detection rate. The environmental factors responsible for the increasing prevalence of the disorder are issues for further studies.
OBJECTIVES: Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. … OBJECTIVES: Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism. METHODS: A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiac disease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored. RESULTS: A total of 34 patients (aged 29–59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8. CONCLUSIONS: “Non-celiac gluten intolerance” may exist, but no clues to the mechanism were elucidated.
Celiac disease is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. It occurs in children and adolescents with gastrointestinal symptoms, dermatitis herpetiformis, dental enamel … Celiac disease is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. It occurs in children and adolescents with gastrointestinal symptoms, dermatitis herpetiformis, dental enamel defects, osteoporosis, short stature, delayed puberty and persistent iron deficiency anemia and in asymptomatic individuals with type 1 diabetes, Down syndrome, Turner syndrome, Williams syndrome, selective immunoglobulin (Ig)A deficiency and first degree relatives of individuals with celiac disease. The Celiac Disease Guideline Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has formulated a clinical practice guideline for the diagnosis and treatment of pediatric celiac disease based on an integration of a systematic review of the medical literature combined with expert opinion. The Committee examined the indications for testing, the value of serological tests, human leukocyte antigen (HLA) typing and histopathology and the treatment and monitoring of children with celiac disease. It is recommended that children and adolescents with symptoms of celiac disease or an increased risk for celiac disease have a blood test for antibody to tissue transglutaminase (TTG), that those with an elevated TTG be referred to a pediatric gastroenterologist for an intestinal biopsy and that those with the characteristics of celiac disease on intestinal histopathology be treated with a strict gluten-free diet. This document represents the official recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition on the diagnosis and treatment of celiac disease in children and adolescents.
Wheat, rye, and barley proteins induce celiac disease, an autoimmune type of gastrointestinal disorder, in genetically susceptible persons. Because the disease may be underdiagnosed, we estimated the prevalence of the … Wheat, rye, and barley proteins induce celiac disease, an autoimmune type of gastrointestinal disorder, in genetically susceptible persons. Because the disease may be underdiagnosed, we estimated the prevalence of the disease and tested the hypothesis that assays for serum autoantibodies can be used to detect untreated celiac disease and that positive findings correlate with specific HLA haplotypes.
Although the prevalence of celiac disease (CD) has been extensively investigated in recent years, an accurate estimate of CD frequency in the European population is still lacking. The aims of … Although the prevalence of celiac disease (CD) has been extensively investigated in recent years, an accurate estimate of CD frequency in the European population is still lacking. The aims of this study were: 1) to establish accurately the prevalence of CD in a large sample of the European population (Finland, Germany, Italy, and UK), including both children and adults; and 2) to investigate whether the prevalence of CD significantly varies between different areas of the European continent.Samples were drawn from the four populations. All 29,212 participants were tested for CD by tissue transglutaminase (tTG) antibody test. Positive and border-line findings were further tested for serum endomysial antibodies (EMA). All serological determinations were centrally performed. Small-bowel biopsies were recommended to autoantibody-positive individuals. Previously diagnosed cases were identified.The overall CD prevalence (previously diagnosed plus anti-tTG and EMA positives) was 1.0% (95% CI 0.9-1.1). In subjects aged 30-64 years CD prevalence was 2.4% in Finland (2.0-2.8), 0.3% in Germany (0.1-0.4), and 0.7% in Italy (0.4-1.0). Sixty-eight percent of antibody-positive individuals showed small-bowel mucosal changes typical for CD (Marsh II/III lesion).CD is common in Europe. CD prevalence shows large unexplained differences in adult age across different European countries.
The pathology and pathologic physiology of celiac disease remain obscure in spite of the many attempts that have been made to understand them. It has become clearer in recent years … The pathology and pathologic physiology of celiac disease remain obscure in spite of the many attempts that have been made to understand them. It has become clearer in recent years that celiac disease is a clinical picture "characterized by arrest of growth, a distended abdomen, and attacks of diarrhoea with large, pale, foul-smelling stools"<sup>1</sup>rather than a disease entity and that the underlying pathologic condition may differ in different cases.<sup>2</sup>A tradition exists that pancreatic steatorrhea can be readily differentiated from idiopathic steatorrhea by the low percentage of split fat in the stools associated with the former and the normal percentage characterizing the latter. A careful survey of the literature, however, reveals few cases of either disease in which careful clinical observations have been followed by adequate postmortem examination. The present study was initiated because of the findings in case 44 (XX), in which a patient with celiac
This guideline presents recommendations for the diagnosis and management of patients with celiac disease. Celiac disease is an immune-based reaction to dietary gluten (storage protein for wheat, barley, and rye) … This guideline presents recommendations for the diagnosis and management of patients with celiac disease. Celiac disease is an immune-based reaction to dietary gluten (storage protein for wheat, barley, and rye) that primarily affects the small intestine in those with a genetic predisposition and resolves with exclusion of gluten from the diet. There has been a substantial increase in the prevalence of celiac disease over the last 50 years and an increase in the rate of diagnosis in the last 10 years. Celiac disease can present with many symptoms, including typical gastrointestinal symptoms (e.g., diarrhea, steatorrhea, weight loss, bloating, flatulence, abdominal pain) and also non-gastrointestinal abnormalities (e.g., abnormal liver function tests, iron deficiency anemia, bone disease, skin disorders, and many other protean manifestations). Indeed, many individuals with celiac disease may have no symptoms at all. Celiac disease is usually detected by serologic testing of celiac-specific antibodies. The diagnosis is confirmed by duodenal mucosal biopsies. Both serology and biopsy should be performed on a gluten-containing diet. The treatment for celiac disease is primarily a gluten-free diet (GFD), which requires significant patient education, motivation, and follow-up. Non-responsive celiac disease occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms should lead to a review of the patient's original diagnosis to exclude alternative diagnoses, a review of the GFD to ensure there is no obvious gluten contamination, and serologic testing to confirm adherence with the GFD. In addition, evaluation for disorders associated with celiac disease that could cause persistent symptoms, such as microscopic colitis, pancreatic exocrine dysfunction, and complications of celiac disease, such as enteropathy-associated lymphoma or refractory celiac disease, should be entertained. Newer therapeutic modalities are being studied in clinical trials, but are not yet approved for use in practice. Given the incomplete response of many patients to a GFD-free diet as well as the difficulty of adherence to the GFD over the long term, development of new effective therapies for symptom control and reversal of inflammation and organ damage are needed. The prevalence of celiac disease is increasing worldwide and many patients with celiac disease remain undiagnosed, highlighting the need for improved strategies in the future for the optimal detection of patients.
In this paper, we review the histological features of coeliac disease and propose a standardized report scheme based on the Marsh classification. Furthermore, terms used by pathologists are defined. The … In this paper, we review the histological features of coeliac disease and propose a standardized report scheme based on the Marsh classification. Furthermore, terms used by pathologists are defined. The most important histological differential diagnoses are given, as well as a definition of the different clinical forms of coeliac disease such as symptomatic, silent, latent, potential, treated and refractory coeliac disease.
Two hundred and ten patients with coeliac disease previously reported from this unit were reviewed at the end of 1985 after a further 11 years of follow up. The initial … Two hundred and ten patients with coeliac disease previously reported from this unit were reviewed at the end of 1985 after a further 11 years of follow up. The initial review at the end of 1974 could not demonstrate that a gluten free diet (GFD) prevented these complications, probably because the time on diet was relatively short. The same series has therefore been kept under surveillance with the particular aim of assessing the effects of diet on malignancy after a further prolonged follow up period. Twelve new cancers have occurred: of which one was a carcinoma of the oesophagus and two lymphomas. Thirty nine cancers developed in 38 patients and of 69 deaths, 33 were the result of malignancy. A two-fold relative risk (RR) of cancer was found and was because of an increased risk of cancer of the mouth and pharynx (RR = 9.7, p less than 0.01, 95% confidence interval (CI) = 2.0-28.3), oesophagus (RR = 12.3, p less than 0.01, CI = 2.5-36.5), and of non-Hodgkin9s lymphoma (RR = 42.7, p less than 0.001, CI = 19.6-81.4). The results indicate that for coeliac patients who have taken a GFD for five years or more the risk of developing cancer over all sites is not increased when compared with the general population. The risk is increased, however, in those taking a reduced gluten, or a normal diet, with an excess of cancers of the mouth, pharynx and oesophagus (RR = 22.7, p &lt; 0.001), and also of lymphoma (RR = 77.8, p &lt; 0.001). A significant decreasing trend in the excess morbidity rate over increasing use of a GFD was found. The results are suggestive of a protective role for a GFD against malignancy in coeliac disease and give further support for advising all patients to adhere to a strict GFD for life.
Two inflammatory disorders, type 1 diabetes and celiac disease, cosegregate in populations, suggesting a common genetic origin. Since both diseases are associated with the HLA class II genes on chromosome … Two inflammatory disorders, type 1 diabetes and celiac disease, cosegregate in populations, suggesting a common genetic origin. Since both diseases are associated with the HLA class II genes on chromosome 6p21, we tested whether non-HLA loci are shared.We evaluated the association between type 1 diabetes and eight loci related to the risk of celiac disease by genotyping and statistical analyses of DNA samples from 8064 patients with type 1 diabetes, 9339 control subjects, and 2828 families providing 3064 parent-child trios (consisting of an affected child and both biologic parents). We also investigated 18 loci associated with type 1 diabetes in 2560 patients with celiac disease and 9339 control subjects.Three celiac disease loci--RGS1 on chromosome 1q31, IL18RAP on chromosome 2q12, and TAGAP on chromosome 6q25--were associated with type 1 diabetes (P<1.00x10(-4)). The 32-bp insertion-deletion variant on chromosome 3p21 was newly identified as a type 1 diabetes locus (P=1.81x10(-8)) and was also associated with celiac disease, along with PTPN2 on chromosome 18p11 and CTLA4 on chromosome 2q33, bringing the total number of loci with evidence of a shared association to seven, including SH2B3 on chromosome 12q24. The effects of the IL18RAP and TAGAP alleles confer protection in type 1 diabetes and susceptibility in celiac disease. Loci with distinct effects in the two diseases included INS on chromosome 11p15, IL2RA on chromosome 10p15, and PTPN22 on chromosome 1p13 in type 1 diabetes and IL12A on 3q25 and LPP on 3q28 in celiac disease.A genetic susceptibility to both type 1 diabetes and celiac disease shares common alleles. These data suggest that common biologic mechanisms, such as autoimmunity-related tissue damage and intolerance to dietary antigens, may be etiologic features of both diseases.
OBJECTIVES: The prevalence of celiac disease (CD) in the United States is unknown. We sought to estimate CD prevalence nationwide by using a nationally representative sample. METHODS: This study included … OBJECTIVES: The prevalence of celiac disease (CD) in the United States is unknown. We sought to estimate CD prevalence nationwide by using a nationally representative sample. METHODS: This study included 7,798 persons aged 6 years or older who participated in the National Health and Nutrition Examination Survey 2009–2010. Serum samples from all participants were tested for immunoglobulin A (IgA) tissue transglutaminase antibodies and, if findings were abnormal, also for IgA endomysial antibodies. Information about prior diagnosis of CD and use of a gluten-free diet (GFD) was obtained by direct interview. CD was defined as having either double-positive serology (serologically diagnosed CD) or a reported diagnosis of CD by a doctor or other health-care professional and being on a GFD (reported clinical diagnosis of CD). RESULTS: CD was found in 35 participants, 29 of whom were unaware of their diagnosis. Median age was 45 years (interquartile range, 23–66 years); 20 were women and 29 were non-Hispanic white. The prevalence of CD in the United States was 0.71% (95% confidence interval (CI), 0.58–0.86%), with 1.01% (95% CI, 0.78–1.31%) among non-Hispanic whites. In all, 55 participants reported following a GFD, which corresponded to a prevalence of 0.63% (95% CI, 0.36–1.07%). CONCLUSIONS: The prevalence of CD in the United States was 0.71% (1 in 141), similar to that found in several European countries. However, most cases were undiagnosed. CD was rare among minority groups but affected 1% of non-Hispanic whites. Most persons who were following a GFD did not have a diagnosis of CD.
Diagnostic criteria for coeliac disease (CD) from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) were published in 1990. Since then, the autoantigen in CD, tissue transglutaminase, has … Diagnostic criteria for coeliac disease (CD) from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) were published in 1990. Since then, the autoantigen in CD, tissue transglutaminase, has been identified; the perception of CD has changed from that of a rather uncommon enteropathy to a common multiorgan disease strongly dependent on the haplotypes human leukocyte antigen (HLA)-DQ2 and HLA-DQ8; and CD-specific antibody tests have improved.A panel of 17 experts defined CD and developed new diagnostic criteria based on the Delphi process. Two groups of patients were defined with different diagnostic approaches to diagnose CD: children with symptoms suggestive of CD (group 1) and asymptomatic children at increased risk for CD (group 2). The 2004 National Institutes of Health/Agency for Healthcare Research and Quality report and a systematic literature search on antibody tests for CD in paediatric patients covering the years 2004 to 2009 was the basis for the evidence-based recommendations on CD-specific antibody testing.In group 1, the diagnosis of CD is based on symptoms, positive serology, and histology that is consistent with CD. If immunoglobulin A anti-tissue transglutaminase type 2 antibody titers are high (>10 times the upper limit of normal), then the option is to diagnose CD without duodenal biopsies by applying a strict protocol with further laboratory tests. In group 2, the diagnosis of CD is based on positive serology and histology. HLA-DQ2 and HLA-DQ8 testing is valuable because CD is unlikely if both haplotypes are negative.The aim of the new guidelines was to achieve a high diagnostic accuracy and to reduce the burden for patients and their families. The performance of these guidelines in clinical practice should be evaluated prospectively.
The great majority of patients that are intolerant of wheat gluten protein due to celiac disease (CD) are human histocompatibility leukocyte antigen (HLA)-DQ2+, and the remaining few normally express HLA-DQ8. … The great majority of patients that are intolerant of wheat gluten protein due to celiac disease (CD) are human histocompatibility leukocyte antigen (HLA)-DQ2+, and the remaining few normally express HLA-DQ8. These two class II molecules are chiefly responsible for the presentation of gluten peptides to the gluten-specific T cells that are found only in the gut of CD patients but not of controls. Interestingly, tissue transglutaminase (tTG)-mediated deamidation of gliadin plays an important role in recognition of this food antigen by intestinal T cells. Here we have used recombinant antigens to demonstrate that the intestinal T cell response to α-gliadin in adult CD is focused on two immunodominant, DQ2-restricted peptides that overlap by a seven-residue fragment of gliadin. We show that tTG converts a glutamine residue within this fragment into glutamic acid and that this process is critical for T cell recognition. Gluten-specific T cell lines from 16 different adult patients all responded to one or both of these deamidated peptides, indicating that these epitopes are highly relevant to disease pathology. Binding studies showed that the deamidated peptides displayed an increased affinity for DQ2, a molecule known to preferentially bind peptides containing negatively charged residues. Interestingly, the modified glutamine is accommodated in different pockets of DQ2 for the different epitopes. These results suggest modifications of anchor residues that lead to an improved affinity for major histocompatibility complex (MHC), and altered conformation of the peptide–MHC complex may be a critical factor leading to T cell responses to gliadin and the oral intolerance of gluten found in CD.
<h3>Objective</h3> The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. <h3>Design</h3> A multidisciplinary task force of 16 physicians from seven … <h3>Objective</h3> The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. <h3>Design</h3> A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to ‘CD’, the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies. <h3>Results</h3> CD was defined as ‘a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals’. Classical CD was defined as ‘CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.’ ‘Gluten-related disorders’ is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper. <h3>Conclusion</h3> This paper presents the Oslo definitions for CD-related terms.
Abstract A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved … Abstract A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications.
<h3>Background</h3> Celiac disease (CD) is an immune-mediated enteropathic condition triggered in genetically susceptible individuals by the ingestion of gluten. Although common in Europe, CD is thought to be rare in … <h3>Background</h3> Celiac disease (CD) is an immune-mediated enteropathic condition triggered in genetically susceptible individuals by the ingestion of gluten. Although common in Europe, CD is thought to be rare in the United States, where there are no large epidemiologic studies of its prevalence. The aim of this study was to determine the prevalence of CD in at-risk and not-at-risk groups in the United States. <h3>Methods</h3> Serum antigliadin antibodies and anti–endomysial antibodies (EMA) were measured. In EMA-positive subjects, human tissue transglutaminase IgA antibodies and CD-associated human leukocyte antigen DQ2/DQ8 haplotypes were determined. Intestinal biopsy was recommended and performed whenever possible for all EMA-positive subjects. A total of 13 145 subjects were screened: 4508 first-degree and 1275 second-degree relatives of patients with biopsy-proven CD, 3236 symptomatic patients (with either gastrointestinal symptoms or a disorder associated with CD), and 4126 not-at-risk individuals. <h3>Results</h3> In at-risk groups, the prevalence of CD was 1:22 in first-degree relatives, 1:39 in second-degree relatives, and 1:56 in symptomatic patients. The overall prevalence of CD in not-at-risk groups was 1:133. All the EMA-positive subjects who underwent intestinal biopsy had lesions consistent with CD. <h3>Conclusions</h3> Our results suggest that CD occurs frequently not only in patients with gastrointestinal symptoms, but also in first- and second-degree relatives and patients with numerous common disorders even in the absence of gastrointestinal symptoms. The prevalence of CD in symptomatic patients and not-at-risk subjects was similar to that reported in Europe. Celiac disease appears to be a more common but neglected disorder than has generally been recognized in the United States.
A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of … A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.
By running the Swedish twin registry containing about 25,000 pairs of twins of the same sex together with the central national diagnosis register of hospital inpatients, 80 twin pairs suffering … By running the Swedish twin registry containing about 25,000 pairs of twins of the same sex together with the central national diagnosis register of hospital inpatients, 80 twin pairs suffering from inflammatory bowel disease were found. In the ulcerative colitis group one of 16 monozygotic pairs was concordant for the disease, but all the other 20 pairs (dizygotic or unknown zygosity) were discordant. In the Crohn's disease group eight of 18 monozygotic pairs and one of 26 dizygotic pairs were concordant. The proband concordance rate among monozygotic twins was 6.3% for ulcerative colitis and 58.3% for Crohn's disease. The calculated heritability of liability based on monozygotic pairs was 0.53 and 1.0 respectively. Thus heredity as an aetiological factor is stronger in Crohn's disease than in ulcerative colitis. Monozygotic twins with Crohn's disease were more likely to be smokers than monozygotic twins with ulcerative colitis. Smoking did not explain the discordance of twin pairs with either ulcerative colitis, or Crohn's disease. The combination of identical heredity and similar smoking habit is not sufficient to cause disease.
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 … 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.
Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options. A major milestone in the history of celiac … Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options. A major milestone in the history of celiac disease was the identification of tissue transglutaminase as the autoantigen, thereby confirming the autoimmune nature of this disorder. A genetic background (HLA-DQ2/DQ8 positivity and non-HLA genes) is a mandatory determinant of the development of the disease, which occurs with the contribution of environmental factors (e.g., viral infections and dysbiosis of gut microbiota). Its prevalence in the general population is of approximately 1%, with female predominance. The disease can occur at any age, with a variety of symptoms/manifestations. This multifaceted clinical presentation leads to several phenotypes, i.e., gastrointestinal, extraintestinal, subclinical, potential, seronegative, non-responsive, and refractory. Although small intestinal biopsy remains the diagnostic 'gold standard', highly sensitive and specific serological tests, such as tissue transglutaminase, endomysial and deamidated gliadin peptide antibodies, have become gradually more important in the diagnostic work-up of celiac disease. Currently, the only treatment for celiac disease is a life-long, strict gluten-free diet leading to improvement in quality of life, ameliorating symptoms, and preventing the occurrence of refractory celiac disease, ulcerative jejunoileitis, and small intestinal adenocarcinoma and lymphoma. The present review is timely and provides a thorough appraisal of various aspects characterizing celiac disease. Remaining challenges include obtaining a better understanding of still-unclear phenotypes such as slow-responsive, potential (minimal lesions) and seronegative celiac disease. The identification of alternative or complementary treatments to the gluten-free diet brings hope for patients unavoidably burdened by diet restrictions.
ABSTRACT Objectives: The ESPGHAN 2012 coeliac disease (CD) diagnostic guidelines aimed to guide physicians in accurately diagnosing CD and permit omission of duodenal biopsies in selected cases. Here, an updated … ABSTRACT Objectives: The ESPGHAN 2012 coeliac disease (CD) diagnostic guidelines aimed to guide physicians in accurately diagnosing CD and permit omission of duodenal biopsies in selected cases. Here, an updated and expanded evidence‐based guideline is presented. Methods: Literature databases and other sources of information were searched for studies that could inform on 10 formulated questions on symptoms, serology, human leukocyte antigen genetics, and histopathology. Eligible articles were assessed using QUADAS2. GRADE provided a basis for statements and recommendations. Results: Various symptoms are suggested for case finding, with limited contribution to diagnostic accuracy. If CD is suspected, measurement of total serum IgA and IgA‐antibodies against transglutaminase 2 (TGA‐IgA) is superior to other combinations. We recommend against deamidated gliadin peptide antibodies (DGP‐IgG/IgA) for initial testing. Only if total IgA is low/undetectable, an IgG‐based test is indicated. Patients with positive results should be referred to a paediatric gastroenterologist/specialist. If TGA‐IgA is ≥10 times the upper limit of normal (10× ULN) and the family agrees, the no‐biopsy diagnosis may be applied, provided endomysial antibodies (EMA‐IgA) will test positive in a second blood sample. Human leukocyte antigen DQ2‐/DQ8 determination and symptoms are not obligatory criteria. In children with positive TGA‐IgA &lt;10× ULN at least 4 biopsies from the distal duodenum and at least 1 from the bulb should be taken. Discordant results between TGA‐IgA and histopathology may require re‐evaluation of biopsies. Patients with no/mild histological changes (Marsh 0/I) but confirmed autoimmunity (TGA‐IgA/EMA‐IgA+) should be followed closely. Conclusions: CD diagnosis can be accurately established with or without duodenal biopsies if given recommendations are followed.
Celiac disease is a unique autoimmune disorder in which the environmental precipitant, gluten, is known. Originally considered a rare malabsorption syndrome of childhood, celiac disease is now recognized as a … Celiac disease is a unique autoimmune disorder in which the environmental precipitant, gluten, is known. Originally considered a rare malabsorption syndrome of childhood, celiac disease is now recognized as a common condition that may be diagnosed at any age and that affects many organ systems. This review discusses the pathogenesis, diagnosis, and management of the disease.
Revised criteria for diagnosis of coeliac diseaseReport of Working Group of European Society of Paediatric Gastroenterology and NutritionIt is now 20 years since the diagnostic criteria for coeliac disease (subsequently … Revised criteria for diagnosis of coeliac diseaseReport of Working Group of European Society of Paediatric Gastroenterology and NutritionIt is now 20 years since the diagnostic criteria for coeliac disease (subsequently known as the European Society of Paediatric Gastroentero- logy and Nutrition (ESPGAN) criteria) were proposed at the Interlaken meeting of the
Celiac sprue, or gluten-sensitive enteropathy, has a wide spectrum of manifestations and is more common than was previously recognized. New, accurate serologic tests make it easier to diagnose this disease … Celiac sprue, or gluten-sensitive enteropathy, has a wide spectrum of manifestations and is more common than was previously recognized. New, accurate serologic tests make it easier to diagnose this disease and have led to changes in the strategies for clinical management.
Type 1 diabetes (T1D) and celiac disease (CeD) are two strongly associated autoimmune disorders, as they share genetic risk factors and immunopathogenic mechanisms. Several studies suggest an implication of gluten … Type 1 diabetes (T1D) and celiac disease (CeD) are two strongly associated autoimmune disorders, as they share genetic risk factors and immunopathogenic mechanisms. Several studies suggest an implication of gluten proteins, the causative antigen of CeD, in T1D pathogenesis. We investigated whether a gliadin-specific T-cell reactivity is present in the gut mucosa of children with T1D, with or without CeD comorbidity. Thirty-three young children were enrolled (median age 10 years) and divided in five groups based on T1D and/or CeD diagnosis. All patients underwent upper endoscopy for suspicion of CeD or gastrointestinal complaints, and duodenal biopsy specimens were processed for analysis of lymphoid cells phenotype and T cell–mediated reactiveness to gliadin. No substantial differences were found in the percentages of various T-cell subsets between the groups. No gliadin T-cell reactivity was found in T1D children negative for CeD, also in the presence of antibodies neutralizing regulatory cytokines interleukin 10 and transforming growth factor β. By contrast, a marked T-cell response to gliadin was detected in T1D with either potential (positive for CeD-associated autoantibodies and normal mucosa histology) or full-blown CeD (villous atrophy). In conclusion, no adaptive immunity to gluten occurs in the small intestine of T1D children in the absence of CeD comorbidity. Article Highlights It has been hypothesized that dietary proteins act as environmental factors in type 1 diabetes pathogenesis. This study investigated whether gliadin-specific T cells are present in the small intestine of children with type 1 diabetes, without or with celiac disease comorbidity. No sign of gliadin-reactive T cells, either proinflammatory or regulatory, was observed in the gut mucosa of children with type 1 diabetes negative for celiac disease autoimmunity. Interferon-γ producing T cells were detected in gut mucosa biopsy specimens of children with diabetes seropositive for antitissue transglutaminase antibodies. Our study does not support a pathogenic role of intestinal T cell–mediated immunity to gluten in type 1 diabetes pathogenesis.
This in-depth review examines the complex interactions between miRNAs and Celiac disease (CD) across various biological aspects. The discussion begins with an in-depth examination of miRNAs' biogenesis and functional pathways, … This in-depth review examines the complex interactions between miRNAs and Celiac disease (CD) across various biological aspects. The discussion begins with an in-depth examination of miRNAs' biogenesis and functional pathways, highlighting their critical regulatory roles in cellular processes. The exploration extends to CD pathogenesis, elucidating how miRNAs contribute to the aberrant immune response against gluten in the small intestine. We navigate miRNAs' regulatory influence on intestinal development and innate and adaptive immunity, providing a panoramic view of their impact on CD etiology. Some miRNAs, such as miR-449a, miR-192-5p, miR-31-5p, miR-17, miR-30a, miR-638, miR-192, miR-194-5p, and miR-197, are dysregulated in CD and are involved in various pathways, including Notch1, tight junctions, and other pathogenetic pathways. The clinical importance of miRNAs takes center stage, unveiling their potential as diagnostic and prognostic markers and reshaping CD management. Investigating miRNA-based therapeutic interventions opens avenues for precision medicine in modulating CD's immune dysregulation. With clinical advancements such as locked nucleic acid-modified antimiRs that target miR-122 for the treatment of hepatitis C and miR-34a mimics for hepatocellular carcinoma, microRNAs are promising therapeutic targets. Additionally, novel delivery systems such as lipid nanoparticles and tissue-specific conjugates address the crucial challenges of targeted miRNA modulation. Extracellular vesicle miRNAs add a layer of complexity, acting as mediators in CD's systemic effects. Finally, we outline future perspectives, envisioning how the evolving landscape of miRNA research can propel advancements in understanding, diagnosis, and treatment, marking this review as a cornerstone for researchers and clinicians in the dynamic field of miRNAs and CD.
Abstract Objectives Disorders of gut–brain interaction (DGBI) are increasing in prevalence; however, diagnosis remains challenging in the setting of organic diseases. While adult studies have shown overlap between DGBI and … Abstract Objectives Disorders of gut–brain interaction (DGBI) are increasing in prevalence; however, diagnosis remains challenging in the setting of organic diseases. While adult studies have shown overlap between DGBI and celiac disease (CeD), no United States studies have assessed DGBI prevalence using Rome IV criteria in pediatric CeD. This study aims to report DGBI prevalence in pediatric CeD patients adherent to gluten‐free diet (GFD) with declining serologies and identify common DGBI subtypes and predictive factors for developing DGBI. Methods Single‐center, retrospective study of children (4–21 years old) with biopsy‐proven CeD who were evaluated for DGBI based on Rome IV criteria. Patients who were adherent to a GFD, demonstrated tissue transglutaminase immunoglobulin A (TTG IgA) decline, and had at least one visit 9–24‐months after diagnosis with a pediatric gastroenterologist were assessed for the presence or absence of gastrointestinal symptoms at all subsequent follow‐up visits. Predictive factors associated with DGBI diagnosis were evaluated. Results Of the 191 pediatric patients included, 43% ( n = 83) met Rome IV DGBI diagnostic criteria. Functional constipation (27/83, 33%) and functional abdominal pain (24/83, 29%) were the most common DGBI. Abdominal pain, constipation, and vomiting at initial presentation as well as comorbid joint hypermobility, headaches, and chronic musculoskeletal pain increased risk of developing DGBI after serological decline. Conclusions DGBI are common in pediatric CeD patients adherent to a GFD with declining TTG IgA. Clinicians should have a high index of suspicion for DGBI in CeD patients with persistent symptoms despite strict GFD adherence to facilitate diagnosis and management.
Abstract Objectives Several studies suggest that the first immunogenic insult in celiac disease (CeD) could occur during fetal development. The placenta is a key organ that could link the environment … Abstract Objectives Several studies suggest that the first immunogenic insult in celiac disease (CeD) could occur during fetal development. The placenta is a key organ that could link the environment with the genome and future outcomes, including CeD. Our objective is to determine the involvement of placental DNA methylation (DNAm) as potential mediator of the genetic susceptibility to CeD. Methods We used Summary‐data‐based Mendelian Randomization to infer what part of the susceptibility to CeD acts through DNAm in placenta or peripheral blood. We interrogated whether DNAm of the CpGs identified correlated with the expression of adjacent genes in the same tissues, and repeated the procedure only in cases and controls carrying the HLA‐DQ2 risk haplotype. Results We identified 248 and 215 CpGs associated with CeD in placenta and blood, respectively. Among the former, the DNAm of seven CpGs correlated with the placental expression of ZFP57 . In contrast, in the latter group, the most represented gene was RNF5 , with DNAm of 11 CpGs correlating with its expression in blood. In HLA‐DQ2 positive individuals, we observed a decrease of placental CpGs associated with CeD, with a remarkable exception in chromosome 2, close to AHSA2 . In blood, we identified 44 CpGs associated with CeD in the HLA region, with HLA‐DPA1 showing the largest number of DNAm‐expression associations. Conclusions Our results suggest that placenta does not seem to be a crucial effector in CeD, and show potentially causal relationships between blood DNAm and CeD, with independent signals in the HLA, and particularly in the HLA‐DPA1 gene.
O presente artigo tem o objetivo de examinar como a doença celíaca afeta mulheres em idade fértil, incluindo aquelas grávidas ou tentando engravidar, com foco em riscos obstétricos, deficiências nutricionais … O presente artigo tem o objetivo de examinar como a doença celíaca afeta mulheres em idade fértil, incluindo aquelas grávidas ou tentando engravidar, com foco em riscos obstétricos, deficiências nutricionais e abordagens de manejo. Uma revisão bibliográfica descritiva, baseada em artigos publicados entre 2015 e 2025 nas bases PubMed, SciELO, LILACS e Cochrane Library. Foram utilizados os descritores “doença celíaca”, “gestação” e “dieta sem glúten” para identificar trabalhos relevantes. Os resultados indicam que a doença celíaca não tratada é associada a infertilidade, abortos espontâneos, parto prematuro e baixo peso ao nascer. Além disso, foram observadas deficiências nutricionais significativas, como anemia ferropriva, hipocalcemia e níveis insuficientes de vitamina D. A análise demonstrou que a adesão rigorosa à dieta sem glúten reduz significativamente complicações maternas e fetais, melhorando parâmetros nutricionais e desfechos obstétricos. Conclui-se que o diagnóstico precoce, aliado ao acompanhamento multidisciplinar e à educação nutricional, é crucial para minimizar riscos e promover gestação saudável em pacientes celíacas. Destaca-se a necessidade de protocolos clínicos padronizados e suporte psicossocial durante o pré-natal, bem como novas pesquisas para otimizar as diretrizes de manejo.
ABSTRACT Aim Determination of faecal gluten immunogenic peptides (f‐GIP) has recently been proposed as new noninvasive method to detect gluten intake in celiac disease (CD). Our aim was to evaluate … ABSTRACT Aim Determination of faecal gluten immunogenic peptides (f‐GIP) has recently been proposed as new noninvasive method to detect gluten intake in celiac disease (CD). Our aim was to evaluate the use of f‐GIP for the adherence to gluten‐free diet (GFD) and to compare this new marker with traditional methods. Methods We enrolled both newly diagnosed cases and children in follow‐up with CD. Adherence to the GFD was assessed using the Biagi score, IgA anti‐transglutaminase (tTG IgA) and f‐GIP. Results Seventy‐one CD children, 40.8% new diagnosis and 59.2% in follow‐up, were enrolled. Significant differences were found in the levels of faecal GIP between new diagnosis and follow up (median 185.7 ng/mL, IQR 67.8–318.8 ng/mL and 16.6 ng/mL, IQR 6.9–61 ng/mL respectively, p &lt; 0.001). A significant direct correlation was found between faecal GIP and tTG IgA in the total cohort of enrolled patients ( r = 0.5, p &lt; 0.001). In the follow up group, 21.4% tested positive for GIP and, of these GIP + patients, 78% had a high Biagi score. Conclusion Our data shows that faecal GIP offers a precise assessment of even occasional exposure to gluten and suggests it might represent a less invasive instrument to check dietary adherence compared to traditional methods.
Celiac disease (CeD) is an autoimmune disorder that is triggered by gluten ingestion in genetically predisposed individuals. Untreated or poorly controlled CeD leads to various disease complications, such as malnutrition, … Celiac disease (CeD) is an autoimmune disorder that is triggered by gluten ingestion in genetically predisposed individuals. Untreated or poorly controlled CeD leads to various disease complications, such as malnutrition, osteoporosis, autoimmune diseases, or refractory celiac disease (RCD). Accumulating recent research has highlighted the association between CeD and the development of malignancies, particularly enteropathy-associated T-cell lymphoma (EATL) and small bowel carcinoma (SBC), which are neoplasms with extremely poor prognoses. Genetic alterations in the JAK1-STAT3 pathway and the high prevalence of microsatellite instability may be the main drivers of CeD-associated lymphomagenesis and small bowel oncogenesis and therefore could be an attractive therapeutic target to block cancer transformation. However, to date, the risk factors and exact mechanisms underlying malignancy development in patients with CeD remain unclear, and prospective cohort studies that include molecular profiling are needed. Moreover, current guidelines on the management of CeD do not provide standardized protocols for cancer surveillance-particularly regarding screening intervals, risk stratification, and monitoring strategies for high-risk patients such as those with RCD. This paper reviews the existing knowledge on malignancies in CeD, highlights diagnostic challenges, and discusses future perspectives on the early detection, monitoring, and treatment of CeD-associated neoplasms.
Background/Objectives: Coeliac disease is an immune-mediated disorder of the gastrointestinal tract that may result in significant nutritional deficiencies. Effective management requires strict, lifelong adherence to a gluten-free diet. Both underdiagnosis … Background/Objectives: Coeliac disease is an immune-mediated disorder of the gastrointestinal tract that may result in significant nutritional deficiencies. Effective management requires strict, lifelong adherence to a gluten-free diet. Both underdiagnosis and unnecessary dietary restrictions can adversely affect patients' health and quality of life. To assess adherence to the current recommendations for the laboratory diagnosis of coeliac disease and promote evidence-based practices while reducing inter-laboratory variability, the Spanish Group on Autoimmunity of the Spanish Society of Immunology conducted a nationwide survey. Methods: A thirty-item survey was distributed to fifty autoimmune laboratories across Spain. Data were collected through a structured Excel-based questionnaire comprising multiple-choice items, which was distributed via email to the participating laboratories. It explored practices related to the diagnosis of coeliac disease in the general population and among at-risk groups as well as approaches to patient follow-up and demand management. Results: Thirty-five laboratories completed the electronic questionnaire. For the serological screening of coeliac disease, all the respondents reported using IgA anti-tissue transglutaminase (tTG-IgA) antibody testing together with total IgA measurement to assess IgA competence. However, consistent use of anti-endomysial antibody testing and HLA genotyping and adherence to pre-analytical recommendations for accurate interpretation of results were not uniform across centres. Conclusions: At the time these data were collected (the third trimester of 2021), the 2020 ESPGHAN guidelines for the diagnosis of coeliac disease in the paediatric population had not yet been fully implemented in most of the laboratories surveyed. For diagnosing adults, most laboratories adhered to local and European guidelines.
Infections caused by carbapenem-resistant Enterobacterales have steadily multiplied over time, becoming a major threat to healthcare systems due to limited therapeutic options and high case-fatality rates. We studied a patient … Infections caused by carbapenem-resistant Enterobacterales have steadily multiplied over time, becoming a major threat to healthcare systems due to limited therapeutic options and high case-fatality rates. We studied a patient who, after being discharged from an ICU, developed salmonellosis caused by an antibiotic-susceptible S. enteritidis. After undergoing treatment with ciprofloxacin, the patient presented an episode of asymptomatic bacteriuria originated by a carbapenem and ciprofloxacin-resistant S. enteritidis. Whole genome sequencing analysis revealed that both Salmonella isolates belonged to the same strain, and that isolate SEn_T2 acquired a plasmid carrying both blaNDM-1 and qnrA1 genes (pIncCSEn) which was previously present in the patient's gut in at least one Enterobacter cloacae isolate. Additionally, pIncCSEN was identified as a putatively new sub-lineage of IncC2 plasmids which lacked the first copy of the methyltransferase gene dcm and the rhs gene. The resistance genes blaNDM-1 and qnrA1 were incorporated into a Tn21-derived transposon that included a complex class 1 integron whose genetic arrangement was: intI1- dfrA12- orfF- aadA2- qacEΔ1-sul1-ISCR1- trpF- ble- blaNDM-1 (in reverse direction)- ISAba125-ISCR1- qnrA- cmlA1- qacEΔ1-sul1. Antimicrobial persistence and co-selection of antibiotic resistance play an important role in the dissemination of antimicrobial resistance genes; in this regard, a joint effort involving the infection control team, effective antibiotic stewardship, and genomic surveillance could help mitigate the spread of these multidrug resistant microorganisms.
Krisztián Birtalan , Dóra Csikós , János Izer +4 more | Magyar Belorvosi Archívum
A 33 éves nő két olyan betegség miatt járt rendszeresen szakambulanciára, amelyek fogyáshoz is vezethetnek, de mindkét betegsége megfelelően kezeltnek látszott. A szerzők a kivizsgálás buktatóira és a tünetek újraértékelésének … A 33 éves nő két olyan betegség miatt járt rendszeresen szakambulanciára, amelyek fogyáshoz is vezethetnek, de mindkét betegsége megfelelően kezeltnek látszott. A szerzők a kivizsgálás buktatóira és a tünetek újraértékelésének fontosságára hívják fel a figyelmet, de egyben bemutatják a refrakter coeliakia diagnosztikájának nehézségeit is.
This study aimed to determine the efficacy of the De Ritis ratio, which is cheaper and easily accessible compared to celiac antibodies, in the diagnosis of celiac disease and in … This study aimed to determine the efficacy of the De Ritis ratio, which is cheaper and easily accessible compared to celiac antibodies, in the diagnosis of celiac disease and in predicting dietary compliance in follow-up. 152 patients over 18 years of age who were diagnosed with celiac disease during a 4-year period in the gastroenterology department of a tertiary care regional hospital and 237 patients without celiac disease as control group were included. Endoscopy and pathology results, laboratory values and pre-diagnostic De Ritis ratios of both groups were compared. Patients with celiac disease were divided into 2 groups as diet-compliant and diet-incompliant. Laboratory values and De Ritis ratios of these 2 groups at diagnosis and at the end of the first year were compared. There were 152 patients in the celiac group and 237 patients in the control group. AST (p<0.001) and AST/ALT mean value (p<0.001) were higher in the celiac patient group compared to the control group. AST/ALT ratio at the time of diagnosis was similar to the AST/ALT ratio at the end of first year in the diet non-compliant group, but the difference between them was not statistically significant (p=0.945). However, AST/ALT ratio at the end of the first year in diet-compliant celiac patient group was lower than at the time of diagnosis (1.17; 1.02, p<0.001). De Ritis ratio may be a promising inexpensive, simple and easily accessible candidate to help clinicians differentiate Celiac disease and assess disease activity and dietary adherence.
Background : The prevalence of food intolerances (FIs) in 1679 individuals over 18 years of age from Bulgaria and some cross-reactivities between the intolerances to different foods were studied. Method … Background : The prevalence of food intolerances (FIs) in 1679 individuals over 18 years of age from Bulgaria and some cross-reactivities between the intolerances to different foods were studied. Method : A blood test was used: Food Detective – CNS (Cambridge Nutrition Sciences Ltd.) to identify the foodstuffs to which the body exhibits intolerance. The basis of the study is the formation of antibodies of class IgG, which are markers for intolerance to different food groups and food products. Individuals were tested for 46 foods. Results : The most common food intolerances are to cereals (60–90% of the subjects), probably related to the high consumption of such products in Bulgaria; to milk and eggs (about 50–68%); legumes (about 24–43%) and nuts (24–40%); and fish and shellfish (about 12–25%). Gluten intolerance is shown by 41.2% of the subjects. Intolerance to vegetables, fruits, and meat has the lowest relative share in the study. Significant correlations were found for 20 pairs of foods, with a high degree of correlation between simultaneous intolerance to soy, tomatoes, and legumes; peppers and mushrooms; and eggs with peppers, mushrooms, and tomatoes. Conclusion : Specific features of the Bulgarian population in the prevalence of food intolerances and the correlations between them have been identified, contributing to the prevention and treatment of nutritional diseases, overweight, and other eating disorders; optimization of dietary regimens at the individual level; prescription of healthy individual diets; and maintenance of individual health.
Systemic lupus erythematosus (SLE) is an autoimmune disorder branded via over-activation of the immune system, resulting in atypical roles of natural and adaptive immune cells and the making of numerous … Systemic lupus erythematosus (SLE) is an autoimmune disorder branded via over-activation of the immune system, resulting in atypical roles of natural and adaptive immune cells and the making of numerous autoantibodies against nuclear components. The causes and pathogenesis of this disease are not completely realized. The gut microbiota plays a significant character in human health and disorder, particularly in autoimmune diseases.Gut microbiome dysbiosis can affect the host immune system as suggested by several recent studies, balance and activity of the gut microbiome, which are influenced by daily diet, might be associated with disease activity in SLE. There are rising signs to support the immunomodulatory abilities of certain probiotics. Numerous investigational and clinical surveys have demonstrated the useful effects of certain probiotic bacteria, mainly strains of Lactobacillus and Bifidobacterium, in patients with SLE. Various species of bacteria were found to be positively or negatively associated with SLE gut microbiomes. A better comprehension of the Studying the gut microbiota will provide a good opportunity to identify microbes involved in tolerance in systemic lupus patients. The purpose of this study is to review the existing literature on probiotics that have the ability to restore tolerance and modulate the levels of inflammatory or anti-inflammatory cytokines that play a role in SLE.
Мета дослідження – визначити частоту і особливості клінічного перебігу автоімунного тиреоїдиту у сполученні із автоімунною патологією тонкого кишківника (целіакія, непереносимість глютену без целіакії). Матеріали та методи. Обстежено 173 пацієнти (три … Мета дослідження – визначити частоту і особливості клінічного перебігу автоімунного тиреоїдиту у сполученні із автоімунною патологією тонкого кишківника (целіакія, непереносимість глютену без целіакії). Матеріали та методи. Обстежено 173 пацієнти (три вікові групи: І – 5-20, ІІ – 21-45, ІІІ – 46-60 років) з рівнем антитіл до тиреоїдної пероксидази (АТПО) у крові понад 600 мкМО/мл: n=35 чол./138 жін. Статус щитоподібної залози (ЩЗ) оцінювали за рівнями тиреотропного гормону (ТТГ), вільного тироксину (вТ4) та вільного трийодтироніину (вТ3). Для візуалізації ЩЗ також використовували ультразвукову діагностику. Для верифікації целіакії імунофлюороферментним методом на аналізаторі «ELIA Phadia» визначали антитіла IgA до тканинної трансглютамінази (АТ-tTG IgA) (Од/мл), антитіла IgG до тканинної трансглютамінази (АТ-тtTG IgG) (Од/мл), антитіла IgА до гліадину (деамінізовані пептиди) (АТ-G IgА) (Од/мл), антитіла IgG до гліадину (деамінізовані пептиди) (АТ-G IgG) (Од/мл) та вміст сироваткового імуноглобуліну A (IgA) (г/л) імунотурбідиметричним методом. Статистичну обробку результатів проводили за допомогою Package for Social Sciences v.19.0 (SPSS Inc., США). Результати та висновки. Встановлено, що 32,4% хворих на автоімунний тиреоїдит усіх вікових груп мають високий титр антитіл до тканинної трансглутамінази і/або гліадину. При скринінговому обстеженні в групі хворих на АІТ віком до 20 років позитивний титр АТ-тtTG IgG виявлено у 14,3%, АТ-G IgG у 17,9%, в групі хворих 21-45 років – у 10,5 та 27,6% відповідно; в групі хворих 46-60 років – у 5,8 та 23,2% відповідно. Одночасно позитивний титр IgG та IgA АТ-тtTG і АТ-G спостерігається у 2,3% хворих, що за наявності виразної активності антитиреоїдного імунітету, гіпотиреозу середнього ступеня тяжкості, стертих гастроінтестинальних симптомів та інших неспецифічних позакишкових клінічних ознак дозволяє з високим ступенем вірогідності встановити діагноз «Целіакія». У інших випадках, за наявності тільки підвищеного титру АТ-G IgG, діагностують «Непереносимість глютену без целіакії». Враховуючи низьку частоту (2,89%) високого титру АТ-тtTG та АТ-G класу IgA, застосування їх в якості діагностичних критеріїв при скринінговому обстеженні пацієнтів з АІТ не є доцільним. За наявності поєднаної полігландулярної автоімунної ендокринної патології у сполученні з іншими автоімунними неендокринними захворюваннями проводити діагностику целіакії необхідно з використанням АТ-тtTG та АТ-G як класу IgA, так і IgG. Встановлений лінійний позитивний сильний кореляційний зв’язок (r= 0,83, p=0,01) між рівнями АТ-G IgG і АТ-ТПО доводить, що за високих титрів АТ-ТПО у пацієнтів з АІТ збільшується виразність імунної відповіді на патологічний вплив глютену.
ABSTRACT Stool gluten immunogenic peptide (s‐GIP) measurement is an innovative tool for detecting voluntary and involuntary gluten exposure in patients with coeliac disease. However, the optimal strategy for its clinical … ABSTRACT Stool gluten immunogenic peptide (s‐GIP) measurement is an innovative tool for detecting voluntary and involuntary gluten exposure in patients with coeliac disease. However, the optimal strategy for its clinical use remains unclear. This longitudinal, prospective study evaluated stool sampling twice a week over 28 days, comparing average s‐GIP concentrations with reduced sampling strategies to optimise its clinical application. Testing stool twice within 7 days was practical and accurate for monitoring dietary adherence. This approach effectively balances patient convenience with diagnostic accuracy for routine clinical use.
Four different yeast strains were isolated from industrial gluten-free bread (GFB) purchased from a local supermarket. These strains, including Hyphopichia burtonii, Wickerhamomyces anomalus, Saccharomycopsis fibuligera, and Cyberlindnera fabianii, are responsible … Four different yeast strains were isolated from industrial gluten-free bread (GFB) purchased from a local supermarket. These strains, including Hyphopichia burtonii, Wickerhamomyces anomalus, Saccharomycopsis fibuligera, and Cyberlindnera fabianii, are responsible for spoilage, which consists of white powdery and filamentous colonies due to the fragmentation of hyphae into short-length fragments (dust-type spots) that is typical of the spoilage produced by chalk yeasts. The isolated strains were identified using genomic analysis. Among them, C. fabianii was also isolated, which is a rare ascomycetous opportunistic yeast species with low virulence attributes, uncommonly implicated in bread spoilage. The yeast growth was studied in vitro on Malt Extract Agar (MEA) at two temperatures (20 and 25 °C) and at different Aws (from 0.99 to 0.90). It was inferred that the temperature did not influence the growth. On the contrary, different Aws reduced the growth, but all the yeast strains could grow until a minimum Aw of about 0.90. Different preservatives (ethanol, hop extract, and sorbic and propionic acids) were used to prevent the growth. In MEA, the growth was reduced but not inhibited. In addition, the vapor-phase antimicrobial activity of different preservatives such as ethanol and hop extract was studied in MEA. Both preservatives completely inhibited the yeast growth either at 20 or at 25 °C. Both preservatives were found in GFB slices. Contrary to hop extract, 2% (v/w) ethanol completely inhibited all the strains. The spoilage was also confirmed by the presence of various compounds typically present in yeasts, derived from sugar fermentation and amino acid degradation. These compounds included alcohols, ketones, organic acids, and esters, and they were identified at higher concentrations in the spoiled samples than in the unspoiled samples. The concentration of acetic acid was low only in the spoiled samples, as this compound was consumed by yeasts, which are predominately present in the spoiled samples, to produce acetate esters.
Celiac disease is a gluten-sensitive, immune-mediated enteropathy that occurs in people with a genetic predisposition and leads to inflammation in the small intestine. During its course, characteristic antibodies are produced, … Celiac disease is a gluten-sensitive, immune-mediated enteropathy that occurs in people with a genetic predisposition and leads to inflammation in the small intestine. During its course, characteristic antibodies are produced, which together with histopathological examination of material taken from the intestine, are the main elements of the diagnostic process. Depending on the symptoms present and microscopic changes, we distinguish classical, non-classical, subclinical and potential forms. The most typical presentation, in the form of gastrointestinal symptoms includes diarrhea, abdominal pain and weight disturbances. Atypical symptom, which may involve multiple other systems, are also increasingly observed. The cornerstone of treatment is a lifelong gluten-free diet that excludes all products containing wheat, barley and rye. In most cases, it helps alleviate or resolve symptoms and regenerate the intestinal mucosa. The long diagnostic process, non-adherence to the diet and resistance to treatment pose a high risk of complications at various stages of the disease, so it is important for the patient to cooperate appropriately with the doctor and nutritionist. The purpose of this paper is to review the most common complications of celiac disease and evaluate the impact of an appropriate diet on their course.
Introduction and Objective: Celiac disease (CD) is a common comorbidity in children with type 1 diabetes mellitus (T1DM). Guidelines suggest screening children for CD with IgA antibodies against tissue transglutaminase … Introduction and Objective: Celiac disease (CD) is a common comorbidity in children with type 1 diabetes mellitus (T1DM). Guidelines suggest screening children for CD with IgA antibodies against tissue transglutaminase (anti-tTGA) at time of time T1DM diagnosis. It is known that mildly elevated anti-tTGA can be present in children with T1DM in the absence of diagnosis of CD. We aimed to determine the rate of false positive anti-tTGA in patients with T1DM and to examine the association between patient characteristics and likelihood of having CD. Methods: An IRB-approved retrospective chart review was conducted on children &amp;lt;18 years old receiving care at the University of Chicago. In cohort 1, data was collected via systemic sampling of patient records 01/01/2004 to 5/31/2019. In cohort 2, data was collected from every patient record from 6/1/2020-10/31/2022. Using statistical software (R version 3.6.0), Chi-square, Mann-Whitney U Test, and Fisher's Exact two-tailed tests analysis were performed, and differences were considered significant at values of p &amp;lt; 0.05. Results: Of 373 children with T1DM, 21% had elevated levels of anti-tTGA. Of these, 73% were diagnosed with CD. The false positive rate was 7%. Individuals with a true positive CD screening were more likely to have positive endomysial antibodies (EMA). Individuals with a false positive CD screening were more likely to have CD screening within 6 months of T1DM diagnosis. Age and gender did not affect overall rates of false positivity. Conclusion: Results are consistent with prior studies demonstrating that those with T1DM with a positive EMA are more likely to have CD. In addition, children who were screened for CD closer to their initial diagnosis of T1DM were more likely to falsely screen positive. This suggests guidelines regarding the timing of initial CD screening may need to be adjusted. Disclosure C. Lockwood: None. D. Judkins: None. T. Abbey: None. A. Cherian: None. M. Williams: None. R. Verma: None. K.L. O'Sullivan: None.
Various enteropathies, including immune-mediated (IME) and infection-related conditions, can lead to small intestinal mucosal injury and malabsorption. While immune dysregulation plays a central role in diseases like celiac disease and … Various enteropathies, including immune-mediated (IME) and infection-related conditions, can lead to small intestinal mucosal injury and malabsorption. While immune dysregulation plays a central role in diseases like celiac disease and autoimmune enteropathy, other conditions such as small intestinal bacterial overgrowth (SIBO) and tropical sprue (TS) involve infectious or microbial pathogenesis. Common clinical manifestations include weight loss, chronic diarrhea, and nutritional deficiencies. While celiac disease (CD) remains the most prevalent IME in adults, an expanding spectrum of non-celiac enteropathies has been recognized, including autoimmune enteropathy (AIE), common variable immunodeficiency disease (CVID), olmesartan-induced enteropathy, tropical sprue, and small intestinal bacterial overgrowth. These conditions often present with overlapping clinical, serological, and histological features, complicating their differentiation from CD. Accurate diagnosis is critical for the timely initiation of effective treatment to prevent disease progression and associated complications such as severe malabsorption and enteropathy-associated T-cell lymphoma (EATL). The small intestine plays a dual role in nutrient absorption and immune regulation, making it uniquely vulnerable to immune dysregulation. In IMEs, hyperactive immune responses disrupt intestinal homeostasis, leading to mucosal damage and impaired nutrient absorption. Although CD is the prototypical IME, increasing the recognition of non-celiac IMEs, it highlights the need for a more nuanced approach to small bowel biopsy interpretation. This review explores the histopathological and clinical features of common IMEs, with a focus on distinguishing non-celiac disorders that mimic CD. By enhancing the understanding of these conditions, this review aims to improve diagnostic accuracy, facilitate appropriate therapeutic interventions, and mitigate complications associated with delayed or misdiagnosis. A multidisciplinary approach involving gastroenterologists and pathologists is emphasized to optimize outcomes for patients with IMEs. Immune-mediated enteropathies result from an abnormal immune response of the small intestinal mucosa to non-pathogenic molecules, often leading to malabsorption syndrome. The most common symptoms include weight loss, chronic diarrhea, and nutritional deficiencies. While celiac disease (CD) is the most well-known immune-mediated enteropathy (IME) in adults, other related disorders have been identified in recent years. These conditions share many clinical and histopathological features, therefore making differentiations between them challenging. This study aims to review the most common immune-mediated enteropathies, with a focus on non-celiac disorders that should be considered in the differential diagnosis of celiac disease in small bowel biopsies.
This study explores the causal link between celiac disease (CeD) and osteoporosis and measures the intermediary role of thyroid dysfunction in this relationship. Using genome-wide association studies summary data, we … This study explores the causal link between celiac disease (CeD) and osteoporosis and measures the intermediary role of thyroid dysfunction in this relationship. Using genome-wide association studies summary data, we performed two-sample Mendelian randomization (MR) studies on genetically predicted CeD (11,812 cases, 23,649 individuals) and osteoporosis (462,933 samples, 7547 cases). We applied two-step MR to quantify the influence of CeD on osteoporosis, two-sample MR to validate the effects of potential mediators (type 1 and 2 diabetes, hyperthyroidism, hypothyroidism), and multivariate MR to estimate the effects of hyperthyroidism and hypothyroidism, and their joint influence. CeD contributes to the risk of osteoporosis (OR: 1.001, 95% CI: 1.000–1.001, P = 4.36E-07) and promotes both hyperthyroidism (OR: 1.001, 95% CI: 1.000–1.002, P = .0003) and hypothyroidism (OR: 1.004, 95% CI: 1.002–1.005, P = 2.24E-06). Hyperthyroidism and hypothyroidism account for 3.17% (95% CI: 2.29%, 5.19%) and 2.24% (95% CI: 1.61%, 3.65%) of the total effect of CeD on osteoporosis, respectively. Together, they explain 34.31% (95% CI: 24.72%, 56.05%) of the total effect. Our study confirms the causal effect between CeD and osteoporosis risk, in which thyroid dysfunction plays a mediating role. Increasing population-level thyroid function screening may lower this risk.
Introduction Celiac disease (CD) is a chronic autoimmune disorder that requires strict adherence to a gluten-free diet (GFD) initiated after diagnosis. This limited diet may lead to nutritional deficiencies. The … Introduction Celiac disease (CD) is a chronic autoimmune disorder that requires strict adherence to a gluten-free diet (GFD) initiated after diagnosis. This limited diet may lead to nutritional deficiencies. The aim of this study was to evaluate nutritional intake and dietary adequacy of children with CD having good adherence to a GFD compared with their healthy peers and to assess the contribution of commercial gluten-free products on the daily energy and macronutrient intakes. Methods This cross-sectional case-control study included children with CD (age range, 2–18 years) and age- and sex-matched healthy controls. Demographic characteristics, anthropometric measurements and food consumption (3-day food record) were recorded. The groups were compared for dietary compositions, dietary adequacy, and anthropometric parameters. Results The study compared 51 patients with 54 controls. The patients had significantly lower height-for-age Z-scores and body mass index-for-age Z-scores ( p &amp;lt; 0.05). The dietary daily energy, protein, fat and fiber intakes were significantly lower in the patients than in the healthy controls ( p &amp;lt; 0.05). The mean nutrient adequacy ratio (NAR) for protein, thiamine, calcium, magnesium, iron, zinc and fiber was significantly lower in the patients for both sexes ( p &amp;lt; 0.05 for all) and the mean NAR for vitamin A and folate was lower in the patients in females ( p &amp;lt; 0.05 for all). The mean nutrient adequacy ratio (MAR) of protein, thiamine, calcium, magnesium, iron, zinc and fiber was lower in the patients than in the controls ( p &amp;lt; 0.05 for all). Conclusion A comprehensive dietary assessment for patients with CD may enhance their adaptation to healthy nutrition and facilitate their optimal growth.
Introduction and Objective: Children with a personal and/or family history of celiac disease (CeD) are at increased risk of type 1 diabetes. However, contemporary evidence is needed to inform potential … Introduction and Objective: Children with a personal and/or family history of celiac disease (CeD) are at increased risk of type 1 diabetes. However, contemporary evidence is needed to inform potential routine screening for islet autoantibodies (IA) in this high-risk population. We sought to determine the prevalence of IA in general population children with CeD or a family history of CeD. Methods: The Autoimmunity Screening for Kids (ASK) study screened for GAD, IA-2, insulin, and ZnT8 autoantibodies in 31,968 children from the general Colorado population. Of those, 344 children reported preexisting CeD and 2,082 children had a family history of CeD. Radiobinding and electrochemiluminescence assays were used for screening and confirmation. Results: Of the 344 children with CeD, 6 (1.8%, 95% CI 0.6-3.8%)) were positive for multiple IA and 7 (2.0%, 95% CI 0.8-4.2%)) were positive for a single IA. Of the 2,082 children with a family history of CeD, 25 children (1.2%, 95% CI 0.8-1.8% ) were positive for multiple IA and 39 children (1.9%, 95% CI 1.3-2.6% ) were positive for a single IA. Multiple IA were more likely among children with CeD (OR 3.3, 95% CI 1.4-7.5, p=0.005) or with a family history of CeD (OR 2.1, 95% CI 1.4-3.1, p= 0.0007) compared to children without these characteristics, adjusting for age and sex. Conclusion: The high prevalence of islet autoimmunity among children with a personal or family history of CeD supports a routine screening in these at-risk groups. More studies are needed to determine the optimal cadence of such a screening and effective follow-up of screen-positive children. Disclosure M. Stahl: Other Relationship; Pfizer Inc. Advisory Panel; Takeda Pharmaceutical Company. Consultant; UpToDate. K.M. Simmons: Consultant; Sanofi. Research Support; Sanofi. Advisory Panel; Sanofi, Shoreline Biosciences. F. Dong: None. D. Felipe-Morales: None. E. Liu: Consultant; Takeda Pharmaceutical Company. Other Relationship; UpToDate. M. Rewers: Consultant; Sanofi. Research Support; Sanofi. Funding Collaboration between Breakthrough T1D and The Leona M. And Harry B. Helmsley Charitable Trust (3-SRA-2024-1590-M-B)
Actuality The state of the intestinal barrier has crucial importance in the pathogenesis of celiac disease (CD). Fecal zonulin (FZ) and intestinal fatty acid binding protein (i-FABP) are important components … Actuality The state of the intestinal barrier has crucial importance in the pathogenesis of celiac disease (CD). Fecal zonulin (FZ) and intestinal fatty acid binding protein (i-FABP) are important components in maintaining physiological processes in the intestine and potential biomarkers of enterocyte damage. Aim of study To evaluate FZ and i-FABP levels as markers of small intestine injury in children with CD, depending on the clinical forms and histomorphological changes in the small intestinal mucosa. Materials and methods In 2021–2023 yy, a single-center observational study was conducted among children with newly diagnosed CD.The level of FZ in stool and I-FABP in serum were determined using the Immundiagnostik ELISA kits (Germany). Results Study included 75 patients,control group was 37 healthy children. The intestinal form of the CD was established in 51 (68.0%) patients,the remaining 24 (32.0%) children have CD with extraintestinal manifestations. Among children with classical CD, the mean values of FZ were 157.9 ± 29.8 ng/ml ( p &amp;lt; 0.02 with control), in second group the mean values of FZ were 136.7 ± 17.0 ng/ml, ( p &amp;lt; 0.05 with the control), and a statistically significant difference between the groups was p &amp;lt; 0.02. The i-FABP values in the first group were 2476.9 ± 297.4 pg/ml ( p &amp;lt; 0.05 with control),and in the second −2061.47 ± 291.5 pg/ml. In the group of children with intestinal manifestations of CD, a weak positive correlation relationship was found between FZ and stool frequency ( r = 0.35). In the second group: weak inverse correlations were between FZ and weight, and height ( r = −0.37 and r = −0.36 respectively). I-FABP values in the first group moderately correlated with stool frequency ( r = 0.53). In the group with extraintestinal manifestations, a moderate negative relationship was found between the i-FABP2 level and BMI ( r = −0.53) and a moderate positive relationship between the i-FABP level and antibodies to tissue transglutaminase IgA ( r = 0.58) and a weak positive correlation with histological assessment according to Marsh criteria ( r = 0.34). Conclusions Our study demonstrated a relationship between the clinical manifestations of CD and the levels of FZ and i-FABP. The increase in the values also can serve as marker of increased permeability and damage of the intestinal barrier, which will open up new possibilities for understanding the processes of restoration of the small intestinal mucosa.
ABSTRACT Objective We aimed to evaluate the prevalence of celiac disease (CeD) autoimmunity among young adult individuals in northwest China based on their relevant demographics, clinical characteristics, and laboratory data. … ABSTRACT Objective We aimed to evaluate the prevalence of celiac disease (CeD) autoimmunity among young adult individuals in northwest China based on their relevant demographics, clinical characteristics, and laboratory data. Methods We conducted a cross‐sectional survey of serum CeD prevalence among young students aged 18–23 years who underwent routine physical examinations at the Xinjiang Second Medical College from September 2022 to December 2023. All subjects were tested for total serum immunoglobulin (Ig) A levels. Those with normal total IgA levels were tested for anti‐tissue transglutaminase (tTG)‐IgA and anti‐endomysial antibody (EMA)‐IgA. Individuals with IgA deficiency were tested for anti‐deamidated gliadin peptide (DGP) IgG and anti‐EMA‐IgG. CeD autoimmunity was defined as positivity for both EMA and tTG/DGP antibodies. Results Among the 1464 participants, CeD seropositivity rates were 0.41% for tTG‐IgA and 0.55% for EMA‐IgA, and CeD autoimmunity was prevalent in 0.34%. All seropositive patients had a normal body mass index. The incidence of seropositivity was highest in Tajiks (1.28%), followed by Kazakhs (0.97%), Hans (0.29%), and Uygurs (0.22%) ( p &gt; 0.05). CeD was most frequently associated with elevated transaminase levels (1.87%; p = 0.005). Biochemical tests showed significantly higher alanine aminotransferase levels in CeD‐positive patients ( p = 0.027). Conclusions The prevalence of CeD autoimmunity in the young adult population of northwest China was 0.34%. Since young individuals often lack typical clinical and laboratory features, screening for CeD in the population with gastrointestinal symptoms, related comorbidities, or atypical manifestations is essential for early diagnosis and effective management of the disease.
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