Cohort Of Celiac Disease Patients Research Articles

Celiac Disease: A Forty-Year Analysis in an Italian Referral Center.

Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion. Herein, we assessed clinical, serological and histopathological findings of a single-center, large cohort of CD patients diagnosed and followed-up over forty years. From January 1980 to December 2020, 1547 CD patients (1170 females; age range: 8-81 years; F:M ratio = 3.1:1) were diagnosed in an Italian tertiary referral center. Comorbidities and complications were recorded at diagnosis and during follow-up. CD diagnoses quadrupled after 2000. The most frequent phenotype was the non-classical CD (63.3%), and the most prevalent histotype was Marsh 3C (44.7%). Gastrointestinal manifestations, detectable in 51% of patients, were diarrhea (24.3%), bloating (28%) and aphthous stomatitis (19.7%). The most common CD-associated disorder was osteopenia (59.9%), predominant in females (64.3%); extraintestinal manifestations included anemia (35.8% iron-deficiency; 87% folic acid malabsorption), cryptogenic hypertransaminasemia (27.9%), and recurrent miscarriages (11.5%). Thyroiditis (26.9%), type 1 diabetes mellitus (2.9%), and dermatitis herpetiformis (1.4%) were the most common CD-related autoimmune disorders. Six patients had inflammatory bowel disease. Complications and mortality rate occurred in 1.8% and 1.9%, respectively. This single-center, large cohort analysis confirmed that CD presentation changed over the years, with an increase of non-classical and subclinical clinical phenotypes.

Coeliac disease in the Trøndelag Health Study (HUNT), Norway, a population-based cohort of coeliac disease patients

PurposeCoeliac disease (CD) is a common disorder and affects about 1% of the population worldwide. CD in the Trøndelag Health Study (HUNT) is a population-based cohort study which was established...

Compliance with Gluten Free Diet Is Associated with Better Quality of Life in Celiac Disease.

The quality of life (QOL) of patients with celiac disease (CD) can be altered by both symptoms of the disease and by the restrictions of the gluten-free diet (GFD). The objective was to determine the factors associated with better QOL in a large cohort of CD patients. A link to an online survey was sent to the members of the French Association of Gluten Intolerant People (AFDIAG). The French-Celiac Disease Questionnaire (F-CDQ), scoring from 0 to 100, was used to measure the QOL. Other data collected were sociodemographic characteristics, information on CD, purchasing and consumption habits of gluten-free products, and a self-assessment scale (ranging from 0 to 10) to determine the compliance with the GFD. Among the 907 CD patients who returned the questionnaire, 787 were analyzed (638 women (81%); median age: 49 years; 71% with self-assessed GFD compliance > 8). Their median F-CDQ was 73 (range: 59–82). In multivariate analysis, the main factors associated with a better quality of life were the long duration of the GFD, good compliance with the GFD, and the number of follow-up visits. Compliance with and duration of the GFD are associated with a better quality of life in patients with CD. Taking this into consideration would offset its restrictive aspect and improve its adherence.

Association between Elevated TGA-IgA Titers and Older Age at Diagnosis with Absence of HBV Seroconversion in Celiac Children.

Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, “responders” and “non-responders” were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of “non-responders”, aiming to organize surveillance and eventual revaccination strategy.

Elimination of Omega-1,2 Gliadins From Bread Wheat (Triticum aestivum) Flour: Effects on Immunogenic Potential and End-Use Quality.

The omega-1,2 gliadins are a group of wheat gluten proteins that contain immunodominant epitopes for celiac disease (CD) and also have been associated with food allergies. To reduce the levels of these proteins in the flour, bread wheat (Triticum aestivum cv. Butte 86) was genetically transformed with an RNA interference plasmid that targeted a 141 bp region at the 5′ end of an omega-1,2 gliadin gene. Flour proteins from two transgenic lines were analyzed in detail by quantitative two-dimensional gel electrophoresis and tandem mass spectrometry. In one line, the omega-1,2 gliadins were missing with few other changes in the proteome. In the other line, striking changes in the proteome were observed and nearly all gliadins and low molecular weight glutenin subunits (LMW-GS) were absent. High molecular weight glutenin subunits (HMW-GS) increased in this line and those that showed the largest increases had molecular weights slightly less than those in the non-transgenic, possibly due to post-translational processing. In addition, there were increases in non-gluten proteins such as triticins, purinins, globulins, serpins, and alpha-amylase/protease inhibitors. Reactivity of flour proteins with serum IgG and IgA antibodies from a cohort of CD patients was reduced significantly in both transgenic lines. Both mixing time and tolerance were improved in the line without omega-1,2 gliadins while mixing properties were diminished in the line missing most gluten proteins. The data suggest that biotechnology approaches may be used to create wheat lines with reduced immunogenic potential in the context of gluten sensitivity without compromising end-use quality.

Hypersomnolence in Patients With Celiac Disease

SESSION TITLE: Sleep 1 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: Celiac disease is one of the most prevalent auto-immune disorders. It is induced by gluten exposure in genetically susceptible individuals. It is associated with DQ2 (DQA1*05; DQB1*02) and DQ8 (DQA1*03; DQB1*0302) human leukocyte antigen (HLA) genotypes. As narcolepsy also has associations with certain HLA loci (DQB1*0602), we aimed to investigate prevalence of sleep disorders associated with hypersomnolence in a cohort of patients with celiac disease. METHODS: Using Advanced Cohort Explorer software, we retrospectively searched the electronic medical records of patients evaluated at Mayo Clinic in Rochester, MN, between 2000 and mid-2014. We identified 750 cases of biopsy confirmed celiac disease and/or dermatitis herpetiformis. We completed manual search of these medical charts, looking for subjective complaints of hypersomnolence, diagnoses of sleep apnea, restless legs syndrome (RLS), and periodic limb movements of sleep, as well as sleep testing. We defined obstructive sleep apnea (OSA) as confirmed diagnosis, nocturnal positive pressure therapy, or clinical suspicion plus oxygen desaturation index > 8. RESULTS: Out of 750 patients we identified 73 (~10%) had known sleep disorder, sleep consultation, polysomnography, and/or overnight pulse oximetry. The most prevalent disorder was OSA (30 cases). The patients with OSA had median age of 55 years (interquartile range (IQR) 46-65), 53% were male, median body mass index was 35 (IQR 28-41), median ODI was 9.3 (IQR 4-17) and median apnea-hypopnea index was 9 (IQR 6-15). In addition, there were 6 patients with periodic limb movements of sleep, 4 patients with RLS, 2 patients with central sleep apnea, and one patient with diagnosis of narcolepsy with cataplexy (proposed prevalence of 0.13%). Compared to the reported OSA prevalence our cohort of celiac disease patients had somewhat lower prevalence with 4% patients affected. Clinically significant RLS prevalence in literature is about 2-3%, while 0.5% patients in our cohort carried the diagnosis of RLS. The previously reported prevalence of narcolepsy with cataplexy in the literature ranges from 25 to 50 per 100,000 people (0.025%-0.05%). Celiac patient cohort evaluated at Mayo Clinic in Rochester therefore had higher prevalence of narcolepsy, though it was only one patient. CONCLUSIONS: While prevalence of sleep apnea and RLS was somewhat lower in our cohort of celiac patients, narcolepsy was more frequent. However, this needs to be confirmed in the future epidemiological and case-control studies. CLINICAL IMPLICATIONS: Our findings suggest that narcolepsy might be more prevalent in patients with celiac disease than general population. Physicians managing patients with celiac disease therefore should pay attention to complaints of hypersomnolence. DISCLOSURE: The following authors have nothing to disclose: Gaja Shaughnessy, Ali Alsaad, Carl Ruthman, Norlalak Jiramethee, Jose Yataco, Emir Festic No Product/Research Disclosure Information

Determination of B-Cell Epitopes in Patients with Celiac Disease: Peptide Microarrays.

BackgroundMost antibodies recognize conformational or discontinuous epitopes that have a specific 3-dimensional shape; however, determination of discontinuous B-cell epitopes is a major challenge in bioscience. Moreover, the current methods for identifying peptide epitopes often involve laborious, high-cost peptide screening programs. Here, we present a novel microarray method for identifying discontinuous B-cell epitopes in celiac disease (CD) by using a silicon-based peptide array and computational methods.MethodsUsing a novel silicon-based microarray platform with a multi-pillar chip, overlapping 12-mer peptide sequences of all native and deamidated gliadins, which are known to trigger CD, were synthesized in situ and used to identify peptide epitopes.ResultsUsing a computational algorithm that considered disease specificity of peptide sequences, 2 distinct epitope sets were identified. Further, by combining the most discriminative 3-mer gliadin sequences with randomly interpolated3- or 6-mer peptide sequences, novel discontinuous epitopes were identified and further optimized to maximize disease discrimination. The final discontinuous epitope sets were tested in a confirmatory cohort of CD patients and controls, yielding 99% sensitivity and 100% specificity.ConclusionsThese novel sets of epitopes derived from gliadin have a high degree of accuracy in differentiating CD from controls, compared with standard serologic tests. The method of ultra-high-density peptide microarray described here would be broadly useful to develop high-fidelity diagnostic tests and explore pathogenesis.

Prevalence of associated disorders in Indian patients with celiac disease

Celiac disease (CD) is an immune-mediated disorder that may be associated with various diseases that share a similar pathogenic immune mechanism. This study reports on the prevalence of various diseases in a cohort of CD patients in northern India. Patients diagnosed with CD based on modified ESPGHAN criteria were prospectively evaluated for associated concomitant diseases. Of the 363 patients evaluated, 207 (57.0 %) were male. The mean age was 19 years. Seventy-one percent of patients presented with typical diarrheal disease, while 29 % presented with atypical nondiarrheal disease. One or more associated diseases were noted in 70 (19.2 %) patients. Liver diseases were the most common association. Portal hypertension was present in 33 (9 %) patients; chronic liver disease was the underlying cause in 17 patients, while noncirrhotic causes were noted in 16 patients. Type 1 diabetes was seen in 13 and hypothyroidism in 11 patients. Other unreported or rarely reported associated diseases were also found in some of the patients. Associated comorbid diseases are common, and may need to be actively screened, in Indian CD patients.

Season of birth in a nationwide cohort of coeliac disease patients

Background and objectiveGenetic factors alone cannot explain the risk of developing coeliac disease (CD). Children born in summer months are likely to be weaned and introduced to gluten during winter...

Oats in a strictly gluten-free diet is associated with decreased gluten intake and increased serum bilirubin

Summary Background and aims To investigate clinical, nutritional, and laboratory parameters during oats challenge and to cross-sectionally examine the levels of plasma bilirubin in a cohort of coeliac disease patients. Methods Intestinal biopsies, gastrointestinal symptom registration, standard blood tests, anthropometry, weighed food records, and calculations of nutrients and gluten were performed in 19 patients before and after oats challenge (50 g/day). To further investigate bilirubin levels, blood samples were analysed in 136 patients (82 oats consumers) and 141 healthy controls. Results Three of 19 patients developed gastrointestinal symptoms during oats challenge. Compliance with gluten-free diet was good. Dietary fibre intake increased after oats inclusion ( p p Conclusions Gluten-free oats were associated with recommended levels of dietary fibre, and calculated gluten intake was reduced by more than 50%. Gluten-free oats induced higher levels of the anti-oxidant bilirubin in treated coeliac disease patients. This may have positive health implications.

Association of polymorphisms of immune response modifier genes with celiac disease and its clinical forms in the Tomsk population

Association of different alleles of immune response modifier genes IL1B (+3953A1/A2), IL1RN (VNTR), IL4 (3′-UTR G/C), IL4RA (I50V), IL12B (1188A/C), and VDR (F/f and B/b) with celiac disease (CD) and its clinical forms was investigated in a family cohort of CD patients from the Tomsk region (N = 139, including 49 probands, i.e., affected children). The control group comprised 129 healthy Russians from Tomsk. A case-control study did not associate any of the polymorphic markers with CD. In a family-based study, the 3′-UTR G/C polymorphism of IL4 was associated with CD (P = 0.024), its atypical form (P = 0.001), and its complications such as osteopenia (P = 0.039) and autoimmune thyroiditis (P = 0.042). IL4RA and VDR polymorphisms I50V and F/f were associated with the typical form of CD (P = 0.001 and P = 0.009, respectively). In general, associations with CD phenotypes were shown primarily for polymorphisms of the genes involved in Th2 immunity.

The Celtic coincidence — the frequency and clinical characterisation of hereditary haemochromatosis in patients with coeliac disease

Hereditary Haemochromatosis (HH) and Coeliac disease (CD) are common disorders in Northern European populations, particularly the Irish population. To investigate whether there was increased frequency of the two common HFE gene mutations, C282Y and H63D, associated with HH amongst a cohort of CD patients, and to determine the penetrance of the HH associated genotypes in this cohort. HFE genotypes of a cohort of CD patients were determined using standard PCR techniques. HFE allele frequencies were compared to those of a previously reported, ethnically similar, cohort of 800 neonates, using Fishers exact test. Patients with HH-associated genotypes were subsequently evaluated. The C282Y and H63D allele frequencies, 24/222 (11%) and 28/222 (13%) respectively, in the CD patients were similar to those of the neonatal group, 171/1600 (11%) and 242/1600 (15%). Eight patients had HH-associated genotypes, of which two demonstrated biochemical evidence of iron overload. The HFE mutations associated with Hereditary Haemochromatosis are not more common in Irish CD patients.

Fatigue in adult coeliac disease

Fatigue is reported by many adults at the moment of diagnosis of coeliac disease and during follow-up. To evaluate the prevalence, characteristics and associations of fatigue in adult coeliac disease patients. The investigated sample comprised adults from Campania, Italy. A total of 130 coeliac disease patients were consecutively recruited in both treated (59 on gluten-free diet) and untreated conditions (71 on normal diet). The control group was made up of 80 healthy controls. Coeliac disease patients and healthy controls underwent laboratory tests, a set of questionnaires for studying fatigue: visual analogue scale for fatigue, chronic fatigue syndrome questionnaire, fatigue severity scale and a modified version of the Zung self-rating depression scale. Coeliac disease patients showed a significantly lower body mass index than controls (P = 0.0001), lower serum iron (P = 0.04). The entire cohort of coeliac disease patients reported greater modified version of the Zung self-rating depression scale score (P = 0.001), greater visual analogue scale for fatigue score (P = 0.0001) and greater chronic fatigue syndrome questionnaire score (P = 0.0001) compared with healthy controls. Coeliac disease patients on a gluten-free diet had a significantly higher modified version of the Zung self-rating depression scale score than coeliacs on a normal diet (P = 0.001). The prevalence of pathological modified version of the Zung self-rating depression scale score was 17% in all coeliac disease patients and 0% in healthy controls. A significant correlation was found between modified version of the Zung self-rating depression scale score and fatigue scale scores in coeliacs on a normal diet. Presence/absence of gastrointestinal symptoms did not show any significant correlation with modified version of the Zung self-rating depression scale score and fatigue scale scores. In coeliacs on a gluten-free diet, modified version of the Zung self-rating depression scale and fatigue scales scores did not significantly differ from coeliacs on a normal diet and were not related to dietetic compliance. In coeliacs, fatigue is a common finding, which ameliorates with the gluten-free diet and is strictly correlated to depression although coeliacs on a gluten-free diet showed more frequent and more severe depression symptoms than coeliacs on a normal diet.