Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet.

BACKGROUND: The gluten-free diet (GFD) has limitations, and there is intense research in the development of adjuvant therapies. AIM: To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult celiac disease (CeD) patients following their usual GFD. METHODS: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled CeD patients on a long-term GFD. After a 4-wk run-in period, patients were randomized to 4 wk of two AN-PEP capsules (GliadinX; AVI Research, LLC, United States) at each of three meals per day or placebo. Outcome endpoints were: (1) Average weekly stool gluten immunogenic peptides (GIP) between the run-in and end of treatments and between AN-PEP and placebo; (2) celiac symptom index (CSI); (3) CeD-specific serology; and (4) quality of life. Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments. RESULTS: Forty patients were randomized for the intention-to-treat analysis, and three were excluded from the per-protocol assessment. Overall, 628/640 (98.1%) stool samples were collected. GIP was undetectable (< 0.08 µg/g) in 65.6% of samples, and no differences between treatment arms were detected. Only 0.5% of samples had GIP concentrations sufficiently high (> 0.32 µg/g) to potentially cause mucosal damage. Median GIP concentration in the AN-PEP arm was 44.7% lower than in the run-in period. One-third of patients exhibiting GIP > 0.08 µg/g during run-in had lower or undetectable GIP after AN-PEP treatment. Compared with the run- in period, the proportion of symptomatic patients (CSI > 38) in the AN-PEP arm was significantly lower (P < 0.03). AN-PEP did not result in changes in specific serologies. CONCLUSION: This exploratory study conducted in a real-life setting revealed high adherence to the GFD. The AN-PEP treatment did not significantly reduce the overall GIP stool concentration. However, given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm, further clinical research is warranted.

Celiac Disease-Related Conditions: Who to Test?

Celiac disease (CeD) is a chronic immune-mediated condition triggered by gluten consumption in genetically predisposed individuals. Approximately 1% of the general population is affected by the disorder. Disease presentation is heterogeneous and, despite growing awareness among physicians and the public, it continues to be underestimated. The most effective strategy for identifying undiagnosed CeD is proactive case finding through serologic testing in high-risk groups. We reviewed the most recent evidence on the association between CeD and more than 20 conditions. In light of this review, CeD screening is recommended in individuals with (1) autoimmune disease and accompanying symptoms suggestive of CeD; (2) diseases that may mimic CeD (eg, irritable bowel syndrome [IBS], inflammatory bowel disease [IBD], and microscopic colitis); and (3) among patients with conditions with a high CeD prevalence: first-degree relatives, idiopathic pancreatitis, unexplained liver enzyme abnormalities, autoimmune hepatitis, primary biliary cholangitis, hyposplenism or functional asplenia with severe bacterial infection, type 1 diabetes mellitus, Hashimoto's thyroiditis and Graves' disease, Sjögren's syndrome, dermatitis herpetiformis, recurrent aphthous syndrome and enamel defects, unexplained ataxia, peripheral neuropathy, delayed menarche or premature menopause, Down syndrome, Turner syndrome, Williams syndrome, chronic fatigue syndrome, IgA nephropathy, and IgA deficiency. CeD serology should be the initial step in the screening process. However, for patients with any of the aforementioned disorders who are undergoing upper endoscopy, biopsies should be performed to rule out CeD.

Guidelines for best practices in monitoring established coeliac disease in adult patients.

Coeliac disease (CeD) is an immunological disease triggered by the consumption of gluten contained in food in individuals with a genetic predisposition. Diagnosis is based on the presence of small bowel mucosal atrophy and circulating autoantibodies (anti-type 2 transglutaminase antibodies). After diagnosis, patients follow a strict, life-long gluten-free diet. Although the criteria for diagnosis of this disease are well defined, the monitoring phase has been studied less and there is a lack of specific guidelines for this phase. To develop a set of clinical guidelines for CeD monitoring, we followed the Grading of Recommendations Assessment, Development and Evaluation methodology. Statements and recommendations with the level of evidence were developed and approved by the working group, which comprised gastroenterologists, pathologists, dieticians and biostatisticians. The proposed guidelines, endorsed by the North American and European coeliac disease scientific societies, make recommendations for best practices in monitoring patients with CeD based on the available evidence. The evidence level is low for many topics, suggesting that further research in specific aspects of CeD would be valuable. In conclusion, the present guidelines support clinicians in improving CeD treatment and follow-up and highlight novel issues that should be considered in future studies.

Comparison of weekly gluten immunogenic peptide measurement and conventional tools to assess adherence to the gluten-free diet in celiac disease: An observational prospective study.

BACKGROUND: Adherence to the gluten-free diet (GFD) is critical to achieving symptom control and mucosal healing in celiac disease (CeD), but its assessment is difficult. OBJECTIVES: We sought to compare stool gluten immunogenic peptides (GIPs) measurements over a 4-wk period with conventional tools commonly used to monitor compliance with a GFD. METHODS: Consecutive adult patients with CeD attending the Small Bowel Section of the Buenos Aires Gastroenterology Hospital were invited to this observational study and were instructed to collect stool samples on Fridays for 4 consecutive weeks. Weekly mean stool GIP concentration was measured was estimated. GIP results were compared with a self-assessment scale of adherence, specific CeD serology, the celiac symptom index, and the assessment by an expert dietitian. RESULTS: Fifty-three CeD patients were enrolled and those with stool GIP ≥0.65 µg/g/wk (n = 13; 24.5%) had higher serum concentrations of IgA deamidated gliadin peptides (DGPs) antibodies [69 (29-109) compared with 14 (13-29); P = 0.0005] and IgA tissue transglutaminase [42 (14-200) compared with 10 (7-16); P = 0.02], higher proportion of cases with IgA DGP antibodies >20 AU/mL (84.6% compared with 33.3%; P = 0.002), and a higher self-estimated adherence score [5 (4-9) compared with 9 (7-10); P = 0.003]. GIP did not correlate with celiac symptom index scores (55.6% compared with 30.8%; P = 0.9). Expert dietitian assessment identified 69% [odds ratio (OR): 5.25; 95% CI: 1.1-27.2; P = 0.01] of nonadherent cases when high stool GIP. Logistic regression analysis determined that IgA DGP (adjusted OR: 1.1; 95% CI: 1.01-1.11; P = 0.02) and males (adjusted OR: 28.3; 95% CI: 1.1-722.6; P = 0.04) were independently associated with excessive gluten exposure. CONCLUSIONS: Weekly stool GIP identifies gluten exposure that is not always detected by commonly used GFD adherence assessment methods. The higher the concentration of stool GIP, the better the predictive value of serology and dietitian interviews. Stool GIP is a useful and practical test for GFD monitoring, particularly for risky gluten exposure in real-life scenarios.

Serum anti-tissue transglutaminase IgA and prediction of duodenal villous atrophy in adults with suspected coeliac disease without IgA deficiency (Bi.A.CeD): a multicentre, prospective cohort study.

BACKGROUND: Whether coeliac disease in adults can be diagnosed with serology alone remains controversial. We aimed to evaluate the accuracy of serum anti-tissue transglutaminase IgA (tTG-IgA) in the diagnosis of coeliac disease. METHODS: In this multicentre, prospective cohort study, adult participants (aged ≥18 years) with suspected coeliac disease without IgA deficiency who were not on a gluten-free diet and who had a local serum tTG-IgA measurement, were enrolled from Feb 27, 2018, to Dec 24, 2020, by 14 tertiary referral centres (ten from Europe, two from Asia, one from Oceania, and one from South America) to undergo local endoscopic duodenal biopsy. Local serum tTG-IgA was measured with 14 different test brands and concentration expressed as a multiple of each test's upper limit of normal (ULN), and defined as positive when greater than 1 times the ULN. The main study outcome was the reliability of serum tests for the diagnosis of coeliac disease, as defined by duodenal villous atrophy (Marsh type 3 or Corazza-Villanacci grade B). Histology was evaluated by the local pathologist, with discordant cases (positive tTG-IgA without duodenal villous atrophy or negative tTG-IgA with duodenal villous atrophy) re-evaluated by a central pathologist. The reliability of serum tests for the prediction of duodenal villous atrophy was evaluated according to sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) for categorical and continuous data. FINDINGS: We enrolled 436 participants with complete local data on serum tTG-IgA and duodenal histology (296 [68%] women and 140 [32%] men; mean age 40 years [SD 15]). Positive serum tTG-IgA was detected in 363 (83%) participants and negative serum tTG-IgA in 73 (17%). Of the 363 participants with positive serum tTG-IgA, 341 had positive histology (true positives) and 22 had negative histology (false positives) after local review. Of the 73 participants with negative serum tTG-IgA, seven had positive histology (false negatives) and 66 had negative histology (true negatives) after local review. The positive predictive value was 93·9% (95% CI 89·2-98·6), the negative predictive value was 90·4% (85·5-95·3), sensitivity was 98·0% (95·3-100·0), and specificity was 75·0% (66·6-83·4). After central re-evaluation of duodenal histology in 29 discordant cases, there were 348 true positive cases, 15 false positive cases, 66 true negative cases, and seven false negative cases, resulting in a positive predictive value of 95·9% (92·0-99·8), a negative predictive value of 90·4% (85·5-95·3), a sensitivity of 98·0% (95·3-100·0), and a specificity of 81·5% (73·9-89·1). Either using the local or central definition of duodenal histology, the positive predictive value of local serum tTG-IgA increased when the serological threshold was defined at increasing multiples of the ULN (p<0·0001). The AUC for serum tTG-IgA for the prediction of duodenal villous atrophy was 0·87 (95% CI 0·81-0·92) when applying the categorical definition of serum tTG-IgA (positive [>1 × ULN] vs negative [≤1 × ULN]), and 0·93 (0·89-0·96) when applying the numerical definition of serum tTG-IgA (multiples of the ULN). Additional endoscopic findings included peptic gastritis (nine patients), autoimmune atrophic gastritis (three), reflux oesophagitis (31), gastric or duodenal ulcer (three), and Barrett's oesophagus (one). In the 1-year follow-up, a midgut ileum lymphoma was diagnosed in a woman on a gluten-free diet. INTERPRETATION: Our data showed that biopsy could be reasonably avoided in the diagnosis of coeliac disease in adults with reliable suspicion of coeliac disease and high serum tTG-IgA. FUNDING: None.

The role of serology in the diagnosis of coeliac disease.

Serology has significantly revolutionized the knowledge of celiac disease (CD), leading to the identification of unsuspected patients in at-risk CD groups, thereby increasing the number of CD diagnoses compared to the pre-screening era. Several markers for CD with a progressive diagnostic accuracy have been identified over the years, but only three of them, i.e. anti-tissue transglutaminase (anti-tTG), anti-endomysial (EmA) and anti-deamidated gliadin antibodies (DGP) are currently assessed in the daily clinical practice. A thorough review of the literature identified 44 original studies published between 1998 to 2022 for a total of 5098 pediatric and adult CD patients (without selective IgA deficiency) and 11930 disease controls. The results highlighted that anti-tTG IgA exhibited a higher sensitivity for CD (93.4%) than EmA IgA (92.8%), DGP IgG (81.8%) and DGP IgA (83.8%). The specificity of EmA IgA (99%) resulted to be higher than those of anti-tTG IgA (95.8%), DGP IgG (96.4%) and DGP IgA (92.1%). In patients with selective IgA deficiency, a condition closely related to CD, serological screening should include one of the three antibodies of IgG class, since anti-tTG, DGP and EmA have a very similar diagnostic accuracy in this clinical setting. According to age, there are two main diagnostic strategies for CD detection. In children, the revised ESPGHAN 2020 guidelines established that CD could be diagnosed in both symptomatic and asymptomatic children by high anti-tTG IgA titers (>10 times the cut-off) and EmA positivity with no need to obtain duodenal biopsy and HLA typing. In adult patients, although high tTG IgA titers (confirmed by EmA IgA positivity) correlate with villous atrophy, an intestinal biopsy is still considered mandatory for confirming CD diagnosis. Currently, a case finding approach in at-risk groups is preferred to mass screening for CD detection.

Upper gastrointestinal endoscopic findings in celiac disease at diagnosis: A multicenter international retrospective study.

BACKGROUND: Gastroduodenal endoscopy and biopsy following positive specific serology is considered the gold standard to diagnose celiac disease (CeD) in adults. Whether upper endoscopy helps detect comorbid conditions is unknown. AIM: To investigate the prevalence of non-celiac endoscopic findings in patients in whom endoscopy was performed to confirm CeD diagnosis. METHODS: This is an observational, descriptive, multicenter, retrospective study that reports endoscopic findings obtained in adult patients enrolled in local registries from four tertiary centers. We collected data reported on first endoscopy, indicated for investigation of CeD. Diagnosis of CeD was performed by histology (≥ Marsh 2 type mucosal damage) and specific serology. Two European and one North American center included biopsy-confirmed CeD following positive serology. A fourth center (South America) included symptomatic patients undergoing endoscopy, irrespective of CeD serology. The latter cohort included a non-CeD control group. RESULTS: A total of 1328 patients (80% female; 35 years median age) were enrolled, of whom 95.6% had positive specific serology. In 135 patients, endoscopy revealed 163 abnormalities unrelated to CeD (prevalence: 10.1%). Erosive reflux esophagitis (6.4%), gastric erosions (2.0%), and suspicion of esophageal metaplasia (1.2%) were the most common findings. Biopsy-confirmed Barrett's esophagus was infrequent (0.2%). No endoscopic cancer was detected. Older patients (≥ 51 years of age) had a higher prevalence of endoscopic findings than those ≤ 50 (P < 0.01). Within the South American cohort, CeD was associated with a lower rate (8.2%) of comorbid endoscopic findings compared with controls (29.1%; P < 0.001). In the adjusted multivariate analysis of this cohort, having CeD was associated with a 72% reduction in the risk of any endoscopic abnormality (P < 0.0001), and having alarm symptoms was associated with a 37% reduction in the risk of finding at least one endoscopic lesion (P < 0.02). CONCLUSION: In this large multicenter study, young adults with positive CeD serology had few comorbid endoscopic findings. Although patients over 51 years had a high prevalence of non-CeD gastroduodenal mucosal damage, no malignancy or premalignant lesions were found.

Coeliac disease.

Coeliac disease is an autoimmune disorder that primarily affects the small intestine, and is caused by the ingestion of gluten in genetically susceptible individuals. Prevalence in the general population ranges from 0·5% to 2%, with an average of about 1%. The development of the coeliac enteropathy depends on a complex immune response to gluten proteins, including both adaptive and innate mechanisms. Clinical presentation of coeliac disease is highly variable and includes classical and non-classical gastrointestinal symptoms, extraintestinal manifestations, and subclinical cases. The disease is associated with a risk of complications, such as osteoporosis and intestinal lymphoma. Diagnosis of coeliac disease requires a positive serology (IgA anti-transglutaminase 2 and anti-endomysial antibodies) and villous atrophy on small-intestinal biopsy. Treatment involves a gluten-free diet; however, owing to the high psychosocial burden of such a diet, research into alternative pharmacological treatments is currently very active.

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in µm), crypt depth (CrD, in µm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

The global burden of coeliac disease: opportunities and challenges.

Coeliac disease is a systemic disorder characterized by immune-mediated enteropathy, which is caused by gluten ingestion in genetically susceptible individuals. The clinical presentation of coeliac disease is highly variable and ranges from malabsorption through solely extra-intestinal manifestations to asymptomatic. As a result, the majority of patients with coeliac disease remain undiagnosed, misdiagnosed or experience a substantial delay in diagnosis. Coeliac disease is diagnosed by a combination of serological findings of disease-related antibodies and histological evidence of villous abnormalities in duodenal biopsy samples. However, variability in histological grading and in the diagnostic performance of some commercially available serological tests remains unacceptably high and confirmatory assays are not readily available in many parts of the world. Currently, the only effective treatment for coeliac disease is a lifelong, strict, gluten-free diet. However, many barriers impede patients' adherence to this diet, including lack of widespread availability, high cost, cross-contamination and its overall restrictive nature. Routine follow-up is necessary to ensure adherence to a gluten-free diet but considerable variation is evident in follow-up protocols and the optimal disease management strategy is not clear. However, these challenges in the diagnosis and management of coeliac disease suggest opportunities for future research.

Determination of gluten immunogenic peptides for the management of the treatment adherence of celiac disease: A systematic review.

BACKGROUND: Gluten is a complex mixture of proteins with immunogenic peptide sequences triggering the autoimmune activity in patients with celiac disease (CeD). Gluten immunogenic peptides (GIP) are resistant to gastrointestinal digestion and are then excreted via the stool and urine. Most common detection methods applied in the follow-up visits for CeD patients such as serology tests, dietetic interviews, questionnaires, and duodenal biopsy have been proved to be inefficient, invasive, or inaccurate for evaluating gluten-free diet (GFD) compliance. Determination of excreted GIP in stool and urine has been developed as a non-invasive, direct, and specific test for GFD monitoring. AIM: To summarize published literature about the clinical utility of GIP determination in comparison to the tools employed for GFD monitoring. METHODS: PubMed and Web of Science searches were performed using the keywords "gluten immunogenic peptides" or "gluten immunogenic peptide" and a combination of the previous terms with "feces", "stools", "urine", "celiac disease", "gluten-free diet", and "adherence" to identify relevant clinical studies published in English and Spanish between 2012 to January 2021. Reference lists from the articles were reviewed to identify additional pertinent articles. Published articles and abstracts reporting the clinical use of GIP determination in stool and/or urine for the follow-up of patients with CeD in comparison with other tools in use were included. Case reports, commentaries, reviews, conference papers, letters, and publications that did not focus on the aims of this review were excluded. RESULTS: Total of 15 publications were found that involved the use of GIP determination in stool and/or urine to monitor the adherence to the GFD in comparison to other tools. Studies included both children and adults diagnosed with CeD and healthy volunteers. Overall, these preliminary studies indicated that this novel technique was highly sensitive for the detection of GFD transgressions and therefore could facilitate the follow-up of patients with CeD. Tools identified in this work included the CeD-specific serology, dietetic questionnaires, symptomatology, and the duodenal biopsy. Review of the literature revealed that the rates of GFD adherence may vary between 30%-93% using either stool or urine GIP determination, 49%-96% by the serology, 59%-94% using the dietetic questionnaires, 56%-95% by the reported symptoms and 44%-76% with the duodenal biopsy. In addition, the association between the different methods and histological abnormalities (Marsh II-III) was found to be 33%-100% for GIP determination (stool and urine), 25%-39% for CeD-specific serology, 3%-50% for dietetic questionnaires, and 22%-28% for the symptomatology. CONCLUSION: Excreted GIP detection is the precise approach for determining voluntary or involuntary gluten consumption in CeD patients preventing future complications arising from gluten exposure.

Risk perception and knowledge of COVID-19 in patients with celiac disease.

BACKGROUND: We recently demonstrated that the odds of contracting coronavirus disease 2019 (COVID-19) in patients with celiac disease (CeD) is similar to that of the general population. However, how patients with CeD perceive their COVID-19 risk may differ from their actual risk. AIM: To investigate risk perceptions of contracting COVID-19 in patients with CeD and determine the factors that may influence their perception. METHODS: We distributed a survey throughout 10 countries between March and June 2020 and collected data on demographics, diet, COVID-19 testing, and risk perceptions of COVID-19 in patients with CeD. Participants were recruited through various celiac associations, clinic visits, and social media. Risk perception was assessed by asking individuals whether they believe patients with CeD are at an increased risk of contracting COVID-19 when compared to the general population. Logistic regression was used to determine the influencing factors associated with COVID-19 risk perception, such as age, sex, adherence to a gluten-free diet (GFD), and comorbidities such as cardiac conditions, respiratory conditions, and diabetes. Data was presented as adjusted odds ratios (aORs). RESULTS: A total of 10737 participants with CeD completed the survey. From them, 6019 (56.1%) patients with CeD perceived they were at a higher risk or were unsure if they were at a higher risk of contracting COVID-19 compared to the non-CeD population. A greater proportion of patients with CeD perceived an increased risk of contracting COVID-19 when compared to infections in general due to their CeD (56.1% vs 26.7%, P < 0.0001). Consequently, 34.8% reported taking extra COVID-19 precautions as a result of their CeD. Members of celiac associations were less likely to perceive an increased risk of COVID-19 when compared to non-members (49.5% vs 57.4%, P < 0.0001). Older age (aOR: 0.99; 95%CI: 0.99 to 0.99, P < 0.001), male sex (aOR: 0.84; 95%CI: 0.76 to 0.93, P = 0.001), and strict adherence to a GFD (aOR: 0.89; 95%CI: 0.82 to 0.96, P = 0.007) were associated with a lower perception of COVID-19 risk and the presence of comorbidities was associated with a higher perception of COVID-19 risk (aOR: 1.38; 95%CI: 1.22 to 1.54, P < 0.001). CONCLUSION: Overall, high levels of risk perceptions, such as those found in patients with CeD, may increase an individual's pandemic-related stress and contribute to negative mental health consequences. Therefore, it is encouraged that public health officials maintain consistent communication with the public and healthcare providers with the celiac community. Future studies specifically evaluating mental health in CeD could help determine the consequences of increased risk perceptions in this population.

Real-World Gluten Exposure in Patients With Celiac Disease on Gluten-Free Diets, Determined From Gliadin Immunogenic Peptides in Urine and Fecal Samples.

BACKGROUND & AIMS: It is not clear how often patients who are on gluten-free diets (GFDs) for treatment of celiac disease still are exposed to gluten. We studied levels of gluten immunogenic peptides (GIP) in fecal and urine samples, collected over 4 weeks, from patients with celiac disease on a long-term GFD. METHODS: We performed a prospective study of 53 adults with celiac disease who had been on a GFD for more than 2 years (median duration, 8 y; interquartile range, 5-12 y) in Argentina. At baseline, symptoms were assessed by the celiac symptom index questionnaire. Patients collected stool each Friday and Saturday and urine samples each Sunday for 4 weeks. We used a commercial enzyme-linked immunosorbent assay to measure GIP in stool and point-of-care tests to measure GIP in urine samples. RESULTS: Overall, 159 of 420 stool and urine samples (37.9%) were positive for GIP; 88.7% of patients had at least 1 fecal or urine sample that was positive for GIP (median, 3 excretions). On weekends (urine samples), 69.8% of patients excreted GIP at least once, compared with 62.3% during weekdays (stool). The number of patients with a sample that was positive for GIP increased over the 4-week study period (urine samples in week 1 vs week 4: P < .05). Patients with symptoms had more weeks in which GIP was detected in stool than patients without symptoms (P < .05). The number of samples that were positive for GIP correlated with titers of deamidated gliadin peptide IgA in patients' blood samples, but not with levels of tissue transglutaminase. CONCLUSIONS: Patients with celiac disease on a long-term GFD still frequently are exposed to gluten. Assays to detect GIP in stool and urine might be used to assist dietitians in assessment of GFD compliance.

Gluten-Free Diet Reduces Symptoms, Particularly Diarrhea, in Patients With Irritable Bowel Syndrome and Antigliadin IgG.

BACKGROUND & AIMS: Many patients with irritable bowel syndrome (IBS) perceive that their symptoms are triggered by wheat-containing foods. We assessed symptoms and gastrointestinal transit before and after a gluten-free diet (GFD) in unselected patients with IBS and investigated biomarkers associated with symptoms. METHODS: We performed a prospective study of 50 patients with IBS (ROME III, all subtypes), with and without serologic reactivity to gluten (antigliadin IgG and IgA), and 25 healthy subjects (controls) at a university hospital in Hamilton, Ontario, Canada, between 2012 and 2016. Gastrointestinal transit, gut symptoms, anxiety, depression, somatization, dietary habits, and microbiota composition were studied before and after 4 weeks of a GFD. HLA-DQ2/DQ8 status was determined. GFD compliance was assessed by a dietitian and by measuring gluten peptides in stool. RESULTS: There was no difference in symptoms among patients at baseline, but after the GFD, patients with antigliadin IgG and IgA reported less diarrhea than patients without these antibodies (P = .03). Compared with baseline, IBS symptoms improved in 18 of 24 patients (75%) with antigliadin IgG and IgA and in 8 of 21 patients (38%) without the antibodies. Although constipation, diarrhea, and abdominal pain were reduced in patients with antigliadin IgG and IgA, only pain decreased in patients without these antibodies. Gastrointestinal transit normalized in a higher proportion of patients with antigliadin IgG and IgA. Anxiety, depression, somatization, and well-being increased in both groups. The presence of antigliadin IgG was associated with overall reductions in symptoms (adjusted odds ratio compared with patients without this antibody, 128.9; 95% CI, 1.16-1427.8; P = .04). Symptoms were reduced even in patients with antigliadin IgG and IgA who reduced gluten intake but were not strictly compliant with the GFD. In controls, a GFD had no effect on gastrointestinal symptoms or gut function. CONCLUSIONS: Antigliadin IgG can be used as a biomarker to identify patients with IBS who might have reductions in symptoms, particularly diarrhea, on a GFD. Larger studies are needed to validate these findings. ClinicalTrials.gov: NCT03492333.

Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts.

OBJECTIVE: We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients. DESIGN: The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD. RESULTS: Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively. CONCLUSION: Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.

The Risk of Contracting COVID-19 Is Not Increased in Patients With Celiac Disease.

The World Health Organization declared coronavirus disease-2019 (COVID-19) a global pandemic in March 2020. Since then, there are more than 34 million cases of COVID-19 leading to more than 1 million deaths worldwide. Numerous studies suggest that celiac disease (CeD), a chronic immune-mediated gastrointestinal condition triggered by gluten, is associated with an increased risk of respiratory infections.1-3 However, how it relates to the risk of COVID-19 is unknown. To address this gap, we conducted a cross-sectional study to evaluate whether patients with self-reported CeD are at an increased risk of contracting COVID-19.

Probiotics for Celiac Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Many patients with celiac disease (CD) experience persistent symptoms despite adhering to the gluten-free diet. Different studies have assessed the use of probiotics as an adjuvant treatment for CD. We performed a systematic review and meta-analysis to evaluate the efficacy of probiotics in improving gastrointestinal (GI) symptoms and quality of life (QOL) in patients with CD. METHODS: We searched EMBASE, MEDLINE, CINAHL, Web of Science, CENTRAL, and DARE databases up to February 2019 for randomized controlled trials (RCTs) evaluating probiotics compared with placebo for treating CD. We collected data on GI symptoms, QOL, adverse events, serum tumor necrosis factor-α, intestinal permeability, and microbiota composition. RESULTS: We screened 2,831 records and found that 7 articles describing 6 RCTs (n = 279 participants) were eligible for quantitative analysis. Probiotics improved GI symptoms when assessed by the GI Symptoms Rating Scale (mean difference symptom reduction: -28.7%; 95% confidence interval [CI] -43.96 to -13.52; P = 0.0002). There was no difference in GI symptoms after probiotics when different questionnaires were pooled. The levels of Bifidobacteria increased after probiotics (mean difference: 0.85 log colony-forming units (CFU) per gram; 95% CI 0.38-1.32 log CFU per gram; P = 0.0003). There were insufficient data on tumor necrosis factor-a levels or QOL for probiotics compared with placebo. No difference in adverse events was observed between probiotics and placebo. The overall certainty of the evidence ranged from very low to low. DISCUSSION: Probiotics may improve GI symptoms in patients with CD. High-quality clinical trials are needed to improve the certainty in the evidence (see Visual abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B595).

Measurement of Forearm Bone Density by Dual Energy X-Ray Absorptiometry Increases the Prevalence of Osteoporosis in Men With Celiac Disease.

BACKGROUND & AIMS: Guidelines advise measurement of bone mineral density (BMD) in patients with a diagnosis of celiac disease. The lumbar spine (LS) and hip sites are usually measured. Although skeletal sites rich in trabecular bone are believed to be vulnerable to osteoporosis in patients with celiac disease, most studies have not measured the cortical distal 1/3-radius. METHODS: We collected data from 721 patients (mean age, 43.6 years; 68.4% female) with celiac disease who underwent 3-site dual energy x-ray absorptiometry (DXA, at a median 1.22 years after diagnosis). We assessed skeletal site- and sex-specific osteoporosis prevalence and the incremental utility of 1/3-radius measurement by DXA. RESULTS: Mean T- and Z-scores were normal in patients, but 43.3% had osteopenia and 19.6% had osteoporosis. Osteoporosis was found in 12.1% of patients at the LS, 5.3% of patients at the total hip, 7.6% of patients at the femoral neck, and 11.5% of patients at the 1/3-radius. A greater degree of villous atrophy at diagnosis was associated with male sex and lower T-scores at the 1/3-radius (P = .03), but not other skeletal sites. Isolated forearm osteoporosis was detected in 4.9% of patients. A higher proportion of patients with isolated forearm osteoporosis were male and had a greater weight and body mass index (all P < .01, compared to patients with osteoporosis only at other sites). Z-scores were lower at the LS and 1/3-radius and osteoporosis was more common in men than women. In men, the 1/3-radius was the most frequent site for osteoporosis. Among patients 50 years or older, isolated forearm osteoporosis was present in 10.7%. CONCLUSIONS: Based on DXA analysis of patients with celiac disease, the prevalence of osteoporosis appears to be underestimated-particularly in men when BMD at the 1/3-radius is not measured. Degree of villous atrophy is associated with BMD at the 1/3-radius and nearly 5% of patients have osteoporosis limited to that site. Recommendations for osteoporosis screening in patients with celiac disease should include measurement of the distal 1/3-radius in addition to the hip and LS.