Current approaches to diagnosis and treatment of celiac disease: An evolving spectrum

doi:10.1053/gast.2001.22123

Gastroenterology

Volume 120, Issue 3, February 2001, Pages 636-651

https://doi.org/10.1053/gast.2001.22123 Get rights and content

Abstract

Celiac disease (CD) is a syndrome characterized by damage of the small intestinal mucosa caused by the gliadin fraction of wheat gluten and similar alcohol-soluble proteins (prolamines) of barley and rye in genetically susceptible subjects. The presence of gluten in these subjects leads to self-perpetuating mucosal damage, whereas elimination of gluten results in full mucosal recovery. The clinical manifestations of CD are protean in nature and vary markedly with the age of the patient, the duration and extent of disease, and the presence of extraintestinal pathologic conditions. In addition to the classical gastrointestinal form, a variety of other clinical manifestations of the disease have been described, including atypical and asymptomatic forms. Therefore, diagnosis of CD is extremely challenging and relies on a sensitive and specific algorithm that allows the identification of different manifestations of the disease. Serologic tests developed in the last decade provide a noninvasive tool to screen both individuals at risk for the disease and the general population. However, the current gold standard for the diagnosis of CD remains histologic confirmation of the intestinal damage in serologically positive individuals. The keystone treatment of CD patients is a lifelong elimination diet in which food products containing gluten are avoided.

GASTROENTROLOGY 2001;120:636-651

Section snippets

Clinical presentations

The clinical manifestations of CD vary markedly with the age of the patient, the duration and extent of disease, and the presence of extraintestinal pathology (Table 1).Depending on the features at the time of presentation, together with the histologic and immunologic abnormalities at the time of diagnosis, CD can be subdivided into the following clinical forms.

Associated diseases

A number of medical conditions are significantly associated with CD (Table 1). For some of these conditions, sensitivity to gliadin has been conclusively proven or may be implicated (Table 1).

Epidemiology of CD in Europe

In the past 3 decades, a substantial number of epidemiologic studies have been conducted in Europe to establish the frequency of CD, and interesting controversies have arisen. Earlier investigations measured the incidence of CD, namely the number of “new” diagnoses in the study population during a certain period. One of the oldest epidemiologic studies on CD conducted in 1950 established that the cumulative incidence of the disease in England and Wales was 1/8000, whereas an incidence of 1/4000

How to diagnose CD?

The diagnosis of CD is based on 3 key parameters: (1) case identification, (2) screening tests, and (3) definitive tests. These parameters have substantially changed during the past 50 years, thanks to better understanding of the clinical presentation of the disease and the advent of more sensitive and specific diagnostic tools and confirmative tests.

The treatment

Total lifelong avoidance of gluten ingestion remains the cornerstone treatment for the disease. The diet requires ongoing education of patients and their families by both doctors and dieticians. Regional CD support groups are instrumental sources of information and support. One of the major controversies in the treatment of CD relates to the amount of gluten allowed in the diet of CD patients. The National Food Authority has recently redefined the term “gluten-free.” Previously, <0.02% gluten

Future directions

A multidisciplinary research effort to understand the pathogenesis of CD is currently taking place worldwide. This effort is fueled by the appreciation that CD represents a unique example of an autoimmune disease in which the environmental factor(s) that induce the immune response has been identified. Therefore, scientists view CD as a model to tackle key questions on the pathogenic mechanisms involved in other autoimmune diseases (i.e., multiple sceloris, diabetes mellitus, rheumatoid

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It has been proposed that zonulin, a tight junction protein regulator, is involved in the pathogenesis of celiac disease (CD). In this regard, various studies compared the mean serum zonulin in patients with CD and healthy controls. However, this remains a subject of controversy due to contradictory results. Therefore, the goal of the present study was to summarize the findings of studies comparing CD patients’ serum zonulin levels to healthy controls.
We searched PubMed, Scopus, and ISI Web of Science databases up to May 2022. All observational studies measured serum zonulin in adult patients with CD and healthy controls were included without language or date restrictions. The standardized mean differences (SMDs) and standard deviations were pooled using a random-effects model.
Of 708 studies, six studies with 184 CD and 206 control participants were included in the systematic review and meta-analysis. According to a pooled analysis, CD patients had significantly higher zonulin levels than healthy controls (SMD = 1.08 ng/mL; 95% CI = 0.64, 1.52; P < 0.001). Subgroup analyses were performed according to adherence to a gluten-free diet (GFD), zonulin assessment method, and CD diagnosis. The significant effect was maintained in all subgroups.
CD is significantly correlated with a higher level of serum zonulin. Thus, zonulin could be a potential biomarker for the diagnosis of CD, which deserves further investigation.
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The purpose of this study was for the first time to explore the feasibility of terahertz (THz) spectral imaging for the detection of gluten contents in food samples. Based on the obtained 80 THz spectrum data, Gaussian process regression (GPR) and support vector machine (SVM) models were established to predict wheat gluten concentrations in 40 potato starch mixture samples. The prediction performances of GPR and SVM obtained were $R^{2}$ = 0.859 and RMSE = 0.070, and $R^{2}$ = 0.715 and RMSE = 0.101 in the gluten concentration range of 1.3%-100%, respectively, showing that the linear SVM algorithm had better prediction performance. The results indicated that THz spectral imaging combined with GPR could be used to predict the gluten content in food samples. It is thus hoped that this research should provide a novel technique for gluten content detection to ensure gluten-free food samples.
Enhancing zein-starch dough and bread properties by addition of hydrocolloids
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Similar to gluten, zein can form a viscoelastic network upon hydration and shear. This makes zein a promising protein to develop gluten-free bakery products. In this study, the effect of addition of different hydrocolloids (hydroxypropyl methylcellulose (HPMC), guar and xanthan gum), and the inclusion of pregelatinized starch (PG starch) and lactic acid (LA) on zein-corn starch dough and bread properties was examined. The addition of HPMC, and to a lesser extent guar gum, significantly changed the viscoelastic zein dough properties and resulted in bread samples with improved loaf volume and sensory properties. Scanning electron microscopy revealed the formation of a continuous fine foam-like structure in the zein-starch dough when HPMC and guar gum were added. This finer structure translated in a lower dough stiffness and resistance to deformation, and a higher degree of deformation characterized by lower complex moduli and increased creep compliance values. Xanthan gum addition, conversely, had an adverse effect on zein bread loaf volume which was attributed to potential weak repulsion between xanthan and zein molecules. In addition, the amount of α-helix and β-sheet secondary structures in bread samples was altered upon hydrocolloid and PG starch addition and played a role in bread crumb hardness. Overall, the zein bread with HPMC showed textural properties most similar to gluten bread. This research sheds light on different structure levels of zein-based gluten-free recipes as affected by inclusion of hydrocolloids, PG starch and LA, and provides a sound basis for the rational development of zein-based gluten-free breads.
Biogeographic Variation and Functional Pathways of the Gut Microbiota in Celiac Disease
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Genes and gluten are necessary but insufficient to cause celiac disease (CeD). Altered gut microbiota has been implicated as an additional risk factor. Variability in sampling site may confound interpretation and mechanistic insight, as CeD primarily affects the small intestine. Thus, we characterized CeD microbiota along the duodenum and in feces and verified functional impact in gnotobiotic mice.
We used 16S rRNA gene sequencing (Illumina) and predicted gene function (PICRUSt2) in duodenal biopsies (D1, D2 and D3), aspirates, and stool from patients with active CeD and controls. CeD alleles were determined in consented participants. A subset of duodenal samples stratified according to similar CeD risk genotypes (controls DQ2^–/– or DQ2^+/– and CeD DQ2^+/–) were used for further analysis and to colonize germ-free mice for gluten metabolism studies.
Microbiota composition and predicted function in CeD was largely determined by intestinal location. In the duodenum, but not stool, there was higher abundance of Escherichia coli (D1), Prevotella salivae (D2), and Neisseria (D3) in CeD vs controls. Predicted bacterial protease and peptidase genes were altered in CeD and impaired gluten degradation was detected only in mice colonized with CeD microbiota.
Our results showed luminal and mucosal microbial niches along the gut in CeD. We identified novel microbial proteolytic pathways involved in gluten detoxification that are impaired in CeD but not in controls carrying DQ2, suggesting an association with active duodenal inflammation. Sampling site should be considered a confounding factor in microbiome studies in CeD.
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Citation Excerpt :
Amylopectin is a highly branched polymer containing α-1,6-glucosidic linkages, and controls the formation of starch granules as well as paste stickiness (Wani et al., 2012). Because rice does not contain gluten as a storage protein, rice flour is a suitable ingredient for people with gluten allergies or who suffer from celiac disease, which is often triggered by the ingestion of gluten-containing foods such as wheat, barley, and rye (Fasano and Catassi, 2001; Heo et al., 2013). However, rice storage proteins lack the viscoelastic properties that are typical of wheat gluten.
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Persons with Coeliac disease (CD) need to keep a lifelong diet without gluten and therefore need to know which foods are safe to eat. The objective of this study was to analyse ordinary foods products without gluten containing ingredients (PWG) with or without the precautionary allergen statement (PAL) “May contain wheat/gluten” or similar wording and use these data to perform a probabilistic risk assessment. Foods with and without PAL were analysed for gluten. Inputs for the risk assessment were analytical results, daily food consumption and data from a 90-days challenge study in coeliac patients (Catassi et al., 2007).20/77 products with PAL and 10/51 without PAL had gluten ≥5 mg/kg 3/77 with PAL and 3/51 without PAL had gluten ≥20 mg/kg. A coconut cookie brand was outlier with 421 mg gluten/kg. The likelihood of developing mucosal damage in the CD population when eating the same PWG for 90 days in addition to certified gluten-free products was low (0.2–3.2%) with little difference between with or without PAL. Including the coconut cookie results increased the risk to 3.8–9.2%.
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^☆: Address requests for reprints to: Alessio Fasano, M.D., Center for Celiac Research, University of Maryland School of Medicine, 685 West Baltimore Street HSF Building, Room 465, Baltimore, Maryland 21201. e-mail: [email protected]; fax: (410) 328-1072.

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Gastroenterology 2001: Diagnostics & TherapeuticsCurrent approaches to diagnosis and treatment of celiac disease: An evolving spectrum☆

Abstract

Section snippets

Clinical presentations

Associated diseases

Epidemiology of CD in Europe

How to diagnose CD?

The treatment

Future directions

Gastroenterology

Lancet

Baillières Clin Gastroenterol

Lancet

J Pediatr

J Pediatr

Lancet

Lancet

Am J Gastroenterol

Lancet

Pediatr Clin North Am

Lancet

Lancet

Lancet

Lancet

Gastroenterology

Gastroenterology

Lancet

Lancet

Lancet

J Clin Epidemiol

J Pediatr

Pediatr Res

Am J Gastroenterol

Lancet

Gastroenterology

Gastroenterology

J Pediatr

J Pediatr

Am J Gastroenterol

Current concepts of celiac disease pathogenesis

Gastroenterology

Structural abnormalities of jejunal epithelial cell membranes in celiac sprue

Lab Invest

Epithelial tight junction structure in the jejunum of children with acute and treated celiac sprue

Pediatr Res

Human zonulin, a potential modulator of intestinal tight junctions

J Cell Sci

Duration of exposure to gluten and risk for autoimmune disorders in celiac patients

Gastroenterology

The foreign antigen binding site and T-cell recognition regions of class I immunohistocompatibility antigens

Nature

Histopathology of intestinal inflammation related to reactive arthritis

Gut

Role of tissue transglutaminase in celiac disease

J Pediatr Gastroenterol Nutr

Identification of tissue transglutaminase as the autoantigen of celiac disease

Nat Med

Changing pattern of childhood coeliac disease in Finland

Acta Paediatr Scand

Changes in clinical features of coeliac disease in adults in Edinburgh and the Lothians 1960-79

BMJ

Is coeliac disease underdiagnosed?

BMJ

Adult coeliac sprue: changes in the pattern of clinical recognition

Gastroenterology

Differences of celiac disease's clinical presentation among pediatric and adults relatives of CD patients in U.S.A

J Invest Med

Diseases associated with dermatitis herpetiformis

Br J Dermatol

Sideropenic anemia and celiac disease: one study, two points of view

Dig Dis Sci

Celiac disease in children of short stature without gastrointestinal symptoms

Eur J Pediatr

Growth failure from symptomless coeliac disease

Helv Paediatr Acta

Catch-up growth in coeliac disease

Acta Paediatr Scand

Gastroenterology, coeliac disease and enamel hypoplasia

Br Dent J

Gastroenterology 2001: Diagnostics & Therapeutics
Current approaches to diagnosis and treatment of celiac disease: An evolving spectrum☆