Untreated Celiac Disease Patients Research Articles

Duodenal mucosa of untreated celiac disease patients has altered expression of the GAS6 and PROS1 and the negative regulator tyrosine kinase TAM receptors subfamily

Celiac disease (CD) is an immune-driven disease characterized by tissue damage in the small intestine of genetically-susceptible individuals. We evaluated here a crucial immune regulatory pathway involving TYRO3, AXL, and MERTK (TAM) receptors and their ligands PROS1 and GAS6 in duodenal biopsies of controls and CD patients. We found increased GAS6 expression associated with downregulation of PROS1 and variable TAM receptors levels in duodenum tissue of CD patients. Interestingly, CD3+ lymphocytes, CD68+, CD11c+ myeloid and epithelial cells, showed differential expressions of TAM components comparing CD vs controls. Principal component analysis revealed a clear segregation of two groups of CD patients based on TAM components and IFN signaling. In vitro validation demonstrated that monocytes, T lymphocytes and epithelial cells upregulated TAM components in response to IFN stimulation. Our findings highlight a dysregulated TAM axis in CD related to IFN signaling and contribute to a deeper understanding of the pathophysiology of CD.

The Second Highest Prevalence of Celiac Disease Worldwide: Genetic and Metabolic Insights in Southern Brazilian Mennonites.

Celiac disease (CD), despite its high morbidity, is an often-underdiagnosed autoimmune enteropathy. Using a modified version of the Brazilian questionnaire of the 2013 National Health Survey, we interviewed 604 Mennonites of Frisian/Flemish origin that have been isolated for 25 generations. A subgroup of 576 participants were screened for IgA autoantibodies in serum, and 391 participants were screened for HLA-DQ2.5/DQ8 subtypes. CD seroprevalence was 1:29 (3.48%, 95% CI = 2.16-5.27%) and biopsy-confirmed CD was 1:75 (1.32%, 95% CI = 0.57-2.59%), which is superior to the highest reported global prevalence (1:100). Half (10/21) of the patients did not suspect the disease. HLA-DQ2.5/DQ8 increased CD susceptibility (OR = 12.13 [95% CI = 1.56-94.20], p = 0.003). The HLA-DQ2.5 carrier frequency was higher in Mennonites than in Brazilians (p = 7 × 10-6). HLA-DQ8 but not HLA-DQ2.5 carrier frequency differed among settlements (p = 0.007) and was higher than in Belgians, a Mennonite ancestral population (p = 1.8 × 10-6), and higher than in Euro-Brazilians (p = 6.5 × 10-6). The glutathione pathway, which prevents reactive oxygen species-causing bowel damage, was altered within the metabolic profiles of untreated CD patients. Those with lower serological positivity clustered with controls presenting close relatives with CD or rheumatoid arthritis. In conclusion, Mennonites have a high CD prevalence with a strong genetic component and altered glutathione metabolism that calls for urgent action to alleviate the burden of comorbidities due to late diagnosis.

Gluten-free diet affects fecal small non-coding RNA profiles and microbiome composition in celiac disease supporting a host-gut microbiota crosstalk

ABSTRACT Current treatment for celiac disease (CD) is adhering to a gluten-free diet (GFD), although its long-term molecular effects are still undescribed. New molecular features detectable in stool may improve and facilitate noninvasive clinical management of CD. For this purpose, fecal small non-coding RNAs (sncRNAs) and gut microbiome profiles were concomitantly explored in CD subjects in relation to strict (or not) GFD adherence over time. In this observational study, we performed small RNA and shotgun metagenomic sequencing in stool from 63 treated CD (tCD) and 3 untreated subjects as well as 66 sex- and age-matched healthy controls. tCD included 51 individuals on strict GFD and with negative transglutaminase (TG) serology (tCD-TG-) and 12 symptomatic with not strict/short-time of GFD adherence and positive TG serology (tCD-TG+). Samples from additional 40 healthy adult individuals and a cohort of 19 untreated pediatric CD subjects and 19 sex/age matched controls were analyzed to further test the outcomes. Several miRNA and microbial profiles were altered in tCD subjects (adj. p < .05). Findings were validated in the external group of adult controls. In tCD-TG-, GFD duration correlated with five miRNA levels (p < .05): for miR-4533-3p and miR-2681-3p, the longer the diet adherence, the less the expression differed from controls. tCD-TG+ and untreated pediatric CD patients showed a similar miRNA dysregulation. Immune-response, trans-membrane transport and cell death pathways were enriched in targets of identified miRNAs. Bifidobacterium longum, Ruminococcus bicirculans, and Haemophilus parainfluenzae abundances shifted (adj. p < .05) with a progressive reduction of denitrification pathways with GFD length. Integrative analysis highlighted 121 miRNA-bacterial relationships (adj. p < .05). Specific molecular patterns in stool characterize CD subjects, reflecting either the long-term GFD effects or the gut inflammatory status, in case of a not strict/short-time adherence. Our findings suggest novel host-microbial interplays and could help the discovery of biomarkers for GFD monitoring over time.

Influence of Gluten-Free Diet on Gut Microbiota Composition in Patients with Coeliac Disease: A Systematic Review.

The aim of this study was to assess the changes in microbiota composition during a gluten-free diet (GFD) in coeliac disease (CD) patients. The systematic search followed databases such as PUBMED (MEDLINE), SCOPUS, WEB OF SCIENCE and EMBASE. Out of 843 initially screened papers, a total number of 13 research papers were included. A total of 212 patients with CD on GFD, in comparison to 174 healthy individuals and 176 untreated patients with CD, were examined. Analysis of the microbial community based primarily on faecal samples and duodenal biopsies. Bifidobacterium was noticed to be less abundant in the study group than in both control groups, while the abundance of Bacteroides was more numerous in the group of CD patients on GFD. Staphylococcaceae prevailed in untreated CD patients. Despite the fact that the GFD was not able to fully restore commensal microorganism abundance, the treatment was associated with the greater abundance of selected beneficial bacteria and lower presence of pathogenic bacteria associated with worsening of CD symptoms.

MO243: Intestinal Fatty-Acid Binding Protein: A Potential Biomarker of Enterocyte Damage in IGA Nephropathy?

Abstract BACKGROUND AND AIMS An abundance of inflammatory cells has been found in duodena of IgA nephropathy (IgAN) patients [1, 2]. The degree of intestinal inflammation was shown to correlate with the amount of proteinuria and haematuria in IgAN [3]. Serum intestinal fatty-acid-binding protein (I-FABP) has shown to correlate with the degree of enterocyte damage in untreated coeliac disease (CD) patients [4]. The median level of I-FABP in untreated CD patients was 785 pg/mL and 173 pg/mL in healthy controls [5]. We conducted this study hypothesizing that I-FABP would be elevated in IgAN as a potential biomarker for the presence of subclinical enterocyte damage and intestinal inflammation. CD was excluded with coeliac autoantibody tests. METHOD This study was carried out at the Tampere University Hospital and Tampere University, Finland. Altogether 85 IgAN patients participated (median age 55 years, 54% males). None of the patients had progressed to end-stage kidney disease, nor had they a diagnosed enteropathy. Fifteen healthy controls (median age 57 years, 47% males) were participants from our previous CD studies. Coeliac autoantibodies were determined from the serum samples by measuring IgA class endomysial antibodies (EmA) and transglutaminase antibodies (tTGAb). EmA was determined by an in-house indirect immunofluorescence method using human umbilical cord as substrate. A serum dilution of 1: ≥ 5 was considered positive. tTGAb levels were determined with EliA Celikey assay (ThermoFisher Scientific, Waltham, MA, USA, cut-off for positivity 7.0 U/mL). The serum levels of I-FABP were determined with a commercially available ELISA kit (Hycult Biotech, Uden, The Netherlands, detection limit 47 pg/mL). Current kidney function was available in 68 IgAN patients (80%), and eGFR &amp;gt;60 mL/min/1.73 m2 was regarded as preserved kidney function. RESULTS I-FABP levels among IgAN patients (median 830 pg/mL, IQR 475–1378) were higher (P &amp;lt; .001) compared with healthy controls (289 pg/mL, IQR 199–568). A total of 57% of the IgAN patients from whom the data on current kidney function were available had preserved kidney function. Also, I-FABP levels in IgAN patients with preserved kidney function (650 pg/mL, IQR 419–880) were higher compared with healthy controls (P .006). tTGAb levels in IgAN patients (1.3, 0.8–1.9 U/mL) were higher (P &amp;lt;.001) compared with healthy controls (0.6, 0.3–0.7 U/mL). One IgAN patient had a borderline elevated tTGAb of 7.1 U/mL. No one had an elevated EmA test result. I-FABP and tTGAb levels had no correlation (rS 0.182, P = .051). CONCLUSION The clear difference in the levels of I-FABP in IgAN patients with preserved kidney function compared with healthy controls was of utmost interest. Elevated I-FABP may represent enterocyte injury and intestinal inflammation present in IgAN. Even though CD was excluded serologically, also the tTGAb levels were higher among IgAN patients. These findings spur us in search for an intestinal process in the pathophysiology of IgAN.

Cell-type-specific gene expression profile by laser capture microdissection on mirror sections

Immuno-laser capture microdissection (Immuno-LCM) has been used to analyze cell-specific gene expression profiles. However, the usefulness of such a technique is frequently limited by RNA degradation. We, therefore, developed a rapid protocol of LCM on mirror sections, which allows for preserving RNA integrity. With such a procedure, we investigated cell-type-specific gene expression of γδ intraepithelial lymphocytes (IELs) in untreated celiac disease (CD).An increase in TGF-β mRNA expression levels was observed in γδ + IELs compared to intestinal enterocytes (IEs), whereas anti-inflammatory IL-10 mRNA production from γδ + IELs was lower compared to IEs.In untreated CD patients, the production of anti-inflammatory cytokines by γδ + IELs is suggestive of a regulatory function, thus playing a critical role in limiting inflammation. This work underscores the importance of LCM on mirror sections as a valuable tool to perform cell-type-specific molecular analysis in tissue.

Toward finding the difference between untreated celiac disease and COVID-19 infected patients in terms of CD4, CD25 (IL-2 R\u03b1), FOXP3 and IL-6 expressions as genes affecting immune homeostasis

BackgroundCoronavirus disease 2019 (COVID-19) is defined as an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 and celiac disease (CD) is one of the autoimmune multiorgan diseases, which can be accompanied by an increased risk of viral infections. CD patients, especially untreated subjects, may be at greater risk of infections such as viral illnesses. Interleukin (IL)-6, CD4, CD25, and FOXP3 are known as genes affecting immune homeostasis and relate to the inflammation state. This study aimed to compare the expression levels of aforementioned genes in peripheral blood samples of CD and severe COVID-19 patients.MethodsSixty newly diagnosed CD patients with median age (mean ± SD) of 35.40 ± 24.12 years; thirty confirmed severe COVID-19 patients with median age (mean ± SD) of 59.67 ± 17.22, and 60 healthy subjects with median age (mean ± SD) of 35.6 ± 13.02 years; were recruited from March to September 2020. Fresh whole blood samples were collected, total RNA was obtained and cDNA synthesis was carried out. RNA expression levels of IL-6, CD4, CD25, and FOXP3 genes were assessed using real-time quantitative RT-PCR according to the 2−∆∆Ct formula. Statistical analysis was performed using SPSS (V.21) and GraphPad, Prism (V.6).ResultsWhile increased expression of CD4, CD25, and FOXP3 was observed in CD patients compared to the control group (p = 0.02, p = 0.03, and p < 0.0001 respectively) and COVID-19 patients group (p < 0.0001 for all of them), their expression levels in COVID-19 patients decreased compared to controls (p < 0.0001, p = 0.01, p = 0.007, respectively). Increased IL-6 expression was observed in both groups of patients compared to controls (p < 0.0001 for both of them).ConclusionsAlthough untreated CD patients may be at greater risk of developing into severe COVID-19 if they are infected by SARS-CoV-2 virus (due to their high expression of IL-6), increased expression of anti-inflammatory markers in these patients may be beneficial for them with the ability of reducing the severity of COVID-19 disease, which needs to be proven in future studies involving celiac patients infected with COVID-19.

Differential expression profile of gluten-specific T cells identified by single-cell RNA-seq.

Gluten-specific CD4+ T cells drive the pathogenesis of celiac disease and circulating gluten-specific T cells can be identified by staining with HLA-DQ:gluten tetramers. In this first single-cell RNA-seq study of tetramer-sorted T cells from untreated celiac disease patients blood, we found that gluten-specific T cells showed distinct transcriptomic profiles consistent with activated effector memory T cells that shared features with Th1 and follicular helper T cells. Compared to non-specific cells, gluten-specific T cells showed differential expression of several genes involved in T-cell receptor signaling, translational processes, apoptosis, fatty acid transport, and redox potentials. Many of the gluten-specific T cells studied shared T-cell receptor with each other, indicating that circulating gluten-specific T cells belong to a limited number of clones. Moreover, the transcriptional profiles of cells that shared the same clonal origin were transcriptionally more similar compared with between clonally unrelated gluten-specific cells.

Back cover story: Eur. J. Immunol. 6'21

European Journal of ImmunologyVolume 51, Issue 6 Back CoverFree Access Back cover story: Eur. J. Immunol. 6'21 First published: 07 June 2021 https://doi.org/10.1002/eji.202170069AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract Our back cover features TRAV and TRBV gene pairing of intraepithelial CD8+ αβ lymphocytes obtained from duodenal biopsies of untreated celiac disease patients. The TRAV/TRBV gene pairing is here depicted using Circos plots. The image is taken from Eggesbø et al. (pp. 1542–1545) where the authors by single-cell TCR sequencing demonstrate that TCR repertoires of celiac disease patients do not show any obvious V gene pairing preference. Furthermore, untreated celiac disease patients display a more polyclonal and diverse TCR repertoire compared to treated patients and healthy subjects. Volume51, Issue6June 2021 RelatedInformation

Relationship between duodenal microbiota composition, clinical features at diagnosis, and persistent symptoms in adult Coeliac disease

BackgroundDuodenal dysbiosis has been suggested to possibly influence the clinical manifestations of coeliac disease (CD), both at onset and when symptoms persist despite a gluten-free diet (GFD). AIMSTo evaluate the relationship between duodenal microbiota composition and: i) clinical phenotype of untreated CD (UCD); ii) presence and type of persistent symptoms despite a satisfactory serological and histological response to a strict GFD. MethodsDuodenal microbiota was analyzed by 16S rRNA sequencing and compared with i) clinical features in 12 adult UCD patients; ii) presence/absence and type of persistent symptoms (diarrhea-predominant vs. non-diarrhea predominant) in 25 adult treated coeliac patients (TCD) on a strict GFD. ResultsUCD with iron deficiency anemia (IDA) had a pro-inflammatory shift in their duodenal microbiota (reduction of Firmicutes, p = 0.03; increase of beta-Proteobacteria, p = 0.02) than those without IDA. TCD with persistent diarrhea showed a reduction of Actinobacteria (p = 0.03) and Rothia spp (p = 0.046) compared to TCD suffering from other type of persistent symptoms. ConclusionA distinctive duodenal microbiota profile is associated with IDA in UCD, and diarrhea-predominant persistent symptoms in TCD. Clinical interventions may include reconsidering patients presenting with IDA as a specific disease subtype, and dietary rebalancing if diarrhea persists despite histological response to a GFD.

Circulating Pv-1 As A Marker of Celiac Disease-Associated Liver Injury

Aim: To investigate the role of endothelial PV-1 in patients with untreated celiac disease (CD)-associated liver injury. Materials & methods: PV-1 and PV-1 mRNA were measured in intestinal biopsies from untreated CD patients with elevated or normal alanine transaminaselevels, controls, patients with inflammatory bowel diseaseand patients with toxic liver injury. Circulating PV-1 levels were also evaluated. Results: Circulating PV-1 levels were significantly increased in the serum of patients with CD-associated liver injury and reverted to normal following a gluten-free diet. Mucosal PV-1 and PV-1 mRNA were no different in patients with CD-associated liver injury. Conclusion: Serum but not mucosal PV-1 represents a marker of gluten-dependent liver injury and response to a gluten-free diet in patients with untreated CD.

Intestinal TG3- and TG2-Specific Plasma Cell Responses in Dermatitis Herpetiformis Patients Undergoing a Gluten Challenge.

Dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is characterized by transglutaminase (TG) 3-targeted dermal immunoglobulin A (IgA) deposits. The treatment for DH is the same as for coeliac disease, namely a life-long gluten-free diet. DH patients typically have gluten-dependent circulating autoantibodies targeting TG3 and TG2, and plasma cells secreting such autoantibodies have been detected in the small intestinal mucosa. This study investigates the gluten-responsiveness of intestinal TG3 and TG2 antibody-secreting plasma cells in 16 treated DH patients undergoing a gluten challenge. The frequency of both plasma cell populations increased significantly during the challenge, and their frequency correlated with the corresponding serum autoantibody levels at post-challenge. TG3-specific plasma cells were absent in all 18 untreated coeliac disease patients and seven non-coeliac control subjects on gluten-containing diets. These findings indicate that, in DH, both intestinal TG3- and TG2-antibody secreting plasma cells are gluten-dependent, and that TG3-antibody secreting plasma cells are DH-specific.

Comparison of thyroid disease prevalence in patients with celiac disease and controls.

This study aimed to investigate the prevalence of thyroid disease (TD) in untreated CD patients and to evaluate the effect of gender and age on its prevalence. Celiac disease (CD) is a form of intestinal malabsorption syndrome which is closely related to endocrine disorders, especially autoimmune thyroid disease and diabetes. The prevalence of TD is possibly high among patients with CD which necessitates the need for screening for TD among them. This comparative cross-sectional study was conducted on 288 consecutive untreated patients with CD (mean age, 27.9±14) and 250 controls (mean age, 29.01±13.15) referred for endoscopy in a hospital located in Iran. Thyroid function was evaluated by measuring T3, T4, and TSH levels using ELISA technique, and testing anti-thyroperoxidase (anti-TPO) antibodies through electrochemiluminescence method. Data analysis was conducted in SPSS v.22 software using descriptive statistics and chi-squared test. Thyroid disease prevalence was 4-fold higher in patients than in controls (13.6% vs. 3.2%, p<0.05). Hypothyroidism was diagnosed in 30 patients and 7 controls, while hyperthyroidism was observed in 9 patients and in one control. Chi-squared test results reported a significant difference in TD prevalence between patients and controls based on gender and age (p<0.05). In both groups, women were significantly more affected than men, and the TD prevalence was higher in younger patients compared to adults. There was a strong association between thyroid dysfunction and CD. In this regard, it is necessary to screen patients for TD.

Motility Disorders in Celiac Disease and Non-Celiac Gluten Sensitivity: The Impact of a Gluten-Free Diet.

Background: There is evidence that digestive motor disorders are frequently present in untreated celiac disease (CD) patients. Similarly, non-celiac gluten sensitivity (NCGS) can be associated with gut motor disorders. In both cases, gut dysmotility can improve or be completely reversed with a gluten-free diet (GFD). Methods: A literature search for motility disorders in CD and NCGS patients was carried out using the online databases PubMed, Medline and Cochrane. Results: Esophageal, gastric, small bowel and gallbladder motor disorders are common in both children and adults with CD. Although the clinical consequences of these disorders are not clearly defined, gastric dysfunction could affect drug absorption and metabolism in the thyroid and neurological conditions associated with CD. The impact of a GFD on motility disorders is, however, controversial. No systematic studies are available on NCGS. NCGS frequently overlaps with irritable bowel syndrome (IBS) and similar pathophysiological mechanisms may be hypothesized. Conclusions: Mucosal damage may affect gut motility in untreated CD through perturbation of hormonal and neuro-immunomodulatory regulation. A persistent low-grade mucosal inflammation could explain the cases of persistent motor disorders despite a GFD. Further studies are needed to definitely assess the role of gut motor disorders in NCGS.

Analysis of IL17A and IL21 Expression in the Small Intestine of Celiac Disease Patients and Correlation with Circulating Thioredoxin Level

Th17 cells and their related cytokines play an important role in the pathogenesis of celiac disease (CD), and thioredoxin (Trx) is an extracellular TG2 activity regulator. This study evaluated Trx serum levels and the expression levels of IL17A, IL21, and Trx genes in biopsies of treated (gluten-free diet) and naïve (untreated) CD patients compared with healthy individuals. Duodenal biopsies were collected from treated CD patients (n = 60), healthy controls (n = 60), and eight newly diagnosed celiac patients. IL17A, IL21, and Trx gene expression was assessed by quantitative polymerase chain reaction (qPCR) and compared with serum Trx levels assessed by enzyme-linked immunosorbent assay (ELISA). Expression levels of the IL21 and Trx genes were not significantly modulated in the CD group compared to the control group, whereas the IL17A gene in CD patients was transcribed at significantly higher levels among the CD group. Serum concentrations of Trx were significantly increased in treated CD patients compared to the control group. We observed that IL17A gene is more highly expressed in duodenal biopsies of CD patients than controls, and that the serum levels of Trx are significantly higher in treated CD patients than controls. Therefore, the expression levels of these genes and gene products, respectively, could potentially be used as diagnostic biomarkers for CD patients, although more studies are needed to unravel the underlying molecular mechanisms.

Coeliac disease and the videocapsule: what have we learned till now.

Celiac disease is diagnosed in part by finding areas of pathology in the small bowel (SB) mucosa. This can often be difficult because the pathologic alterations, including atrophy of the small intestinal villi, can often be sparse and subtle. Some of the quantitative methods for detecting and measuring the presence of villous atrophy from videocapsule endoscopy (VCE) images are presented and discussed. These methods consist of static features of measurement including texture, gray level, and presence and abundance of fissures contained within each acquired image. The methods also consist of dynamic measurements including spectral analysis, and determining motion from a sequence of endoscopic images as obtained from a VCE clip. Thus far, several methods have been found useful to characterize the SB mucosa of untreated celiac disease patients versus control patients lacking villous atrophy, which have revealed significant differences in texture, frequency, and motion on analysis of VCE. In untreated celiac patients undergoing endoscopy, there tends to be greater magnitude of changes and spatial differences in textural descriptors, longer periodic components, indicating slower periodic activity, and differences in feature location, suggesting alterations in motility at areas of pathology as compared to patients without villous atrophy. Improvements in the quantitative analysis of VCE imaging in celiac patients is important to detect pathology in suspected patients, so that biopsies can be obtained from pertinent regions of the small intestinal mucosa. Improvements are also necessary so that patients with celiac disease can be monitored to evaluate the progress of mucosal healing after onset of treatment.

Serum Alkylresorcinols as Biomarkers of Dietary Gluten Exposure in Celiac disease

BackgroundTherapy for celiac disease (CD) mainly relies on following a gluten‐free diet (GFD); however, a serum marker for gluten intake has yet to be established.AimsTo evaluate the utility of alkylresorcinol concentrations for detecting gluten intake in studies of human and mouse.MethodsAlkylresorcinol concentrations were compared among treated CD patients (n=34), untreated CD patients (n=36), and controls (n=33). Furthermore, 7 additional CD patients whose serum samples were available at diagnosis and after GFD were evaluated. In mice studies, alkylresorcinol concentrations were compared in the serum of 5 mice fed a regular chow and 10 mice fed lifelong with a gluten‐free chow. In addition, the effect of adding gluten on changes of alkylresorcinol concentrations was also evaluated.ResultsTotal alkylresorcinol concentrations were significantly lower in treated CD patients (median [IQR], 3 (2–8) nmol/L), compared to untreated CD patients (median [IQR], 32 [11–74] nmol/L; P&lt;.0001) or healthy controls (median [IQR], 54 [23–112] nmol/L; P&lt;.0001). Moreover, alkylresorcinol concentrations in CD patients significantly decreased after introduction of a GFD (median, 34 nmol/L at diagnosis vs. 5 nmol.L after GFD, p=0.02). In the mice, median (IQR) total alkylresorcinol concentrations in serum samples of mice fed lifelong with a gluten‐free chow was 1.8 (1.6–2.3) nmol/L, which was further significantly increased to 16 (11–22) nmol/L after 8 days of feeding with the gluten free chow that had gluten added to it. (p=.008).ConclusionSerum alkylresorcinol concentrations could be a useful marker for dietary gluten in CD.Support or Funding InformationNo funding to report.

Serum alkylresorcinols as biomarkers of dietary gluten exposure in coeliac disease.

Therapy for coeliac disease (CD) mainly relies on following a gluten-free diet (GFD); however, a serum marker for gluten intake has yet to be established. To evaluate the utility of alkylresorcinol concentrations for detecting gluten intake in studies of human and mouse. Alkylresorcinol concentrations were compared among treated patients with coeliac disease (n = 34), untreated coeliac disease patients (n = 36) and controls (n = 33). Furthermore, seven additional coeliac disease patients whose serum samples were available at diagnosis and after GFD were evaluated. In mice studies, alkylresorcinol concentrations were compared in the serum of five mice fed a regular chow and 10 mice fed lifelong with a gluten-free chow. In addition, the effect of adding gluten on changes of alkylresorcinol concentrations was also evaluated. Total alkylresorcinol concentrations were significantly lower in treated with coeliac disease [median (IQR), 3 (2-8) nmol/L], compared to untreated patients [median (IQR), 32 (11-74) nmol/L; P < 0.0001] or healthy controls [median (IQR), 54 (23-112) nmol/L; P < 0.0001]. Moreover, alkylresorcinol concentrations in coeliac disease patients significantly decreased after introduction of a GFD (median, 34 nmol/L at diagnosis vs. 5 nmol/L after GFD, P = 0.02). In the mice, median (IQR) total alkylresorcinol concentrations in serum samples of mice fed lifelong with a gluten-free chow was 1.8 (1.6-2.3) nmol/L, which was further significantly increased to 16 (11-22) nmol/L after 8 days of feeding with the gluten-free chow that had gluten added to it. (P = 0.008). Serum alkylresorcinol concentrations could be a useful marker for dietary gluten in coeliac disease.

Cardiovascular involvement in celiac disease.

Celiac disease (CD) is an autoimmune response to ingestion of gluten protein, which is found in wheat, rye, and barley grains, and results in both small intestinal manifestations, including villous atrophy, as well as systemic manifestations. The main treatment for the disease is a gluten-free diet (GFD), which typically results in the restoration of the small intestinal villi, and restoration of other affected organ systems, to their normal functioning. In an increasing number of recently published studies, there has been great interest in the occurrence of alterations in the cardiovascular system in untreated CD. Herein, published studies in which CD and cardiovascular terms appear in the title of the study were reviewed. The publications were categorized into one of several types: (1) articles (including cohort and case-control studies); (2) reviews and meta-analyses; (3) case studies (one to three patient reports); (4) letters; (5) editorials; and (6) abstracts (used when no full-length work had been published). The studies were subdivided as either heart or vascular studies, and were further characterized by the particular condition that was evident in conjunction with CD. Publication information was determined using the Google Scholar search tool. For each publication, its type and year of publication were tabulated. Salient information from each article was then compiled. It was determined that there has been a sharp increase in the number of CD - cardiovascular studies since 2000. Most of the publications are either of the type “article” or “case study”. The largest number of documents published concerned CD in conjunction with cardiomyopathy (33 studies), and there have also been substantial numbers of studies published on CD and thrombosis (27), cardiovascular risk (17), atherosclerosis (13), stroke (12), arterial function (11), and ischemic heart disease (11). Based on the published research, it can be concluded that many types of cardiovascular issues can occur in untreated CD patients, but that most tend to resolve on a GFD, often in conjunction with the healing of small intestinal villous atrophy. However, in some cases the alterations are irreversible, underscoring the need for CD screening and treatment when cardiovascular issues arise of unknown etiology.

The progression of coeliac disease: its neurological and psychiatric implications.

The aim of the paper is to show the various neurological and psychiatric symptoms in coeliac disease (CD). CD is a T cell-mediated, tissue-specific autoimmune disease which affects genetically susceptible individuals after dietary exposure to proline- and glutamine-rich proteins contained in certain cereal grains. Genetics, environmental factors and different immune systems, together with the presence of auto-antigens, are taken into account when identifying the pathogenesis of CD. CD pathogenesis is related to immune dysregulation, which involves the gastrointestinal system, and the extra-intestinal systems such as the nervous system, whose neurological symptoms are evidenced in CD patients. A gluten-free diet (GFD) could avoid cerebellar ataxia, epilepsy, neuropathies, migraine and mild cognitive impairment. Furthermore, untreated CD patients have more symptoms and psychiatric co-morbidities than those treated with a GFD. Common psychiatric symptoms in untreated CD adult patients include depression, apathy, anxiety, and irritability and schizophrenia is also common in untreated CD. Several studies show improvement in psychiatric symptoms after the start of a GFD. The present review discusses the state of the art regarding neurological and psychiatric complications in CD and highlights the evidence supporting a role for GFD in reducing neurological and psychiatric complications.