Celiac disease is characterized by small intestinal damage with loss of absorptive villi and hyperplasia of the crypts, typically leading to malabsorption. In addition to nutrient deficiencies, prolonged celiac disease is associated with an increased risk for malignancy, especially intestinal T-cell lymphoma. Celiac disease is precipitated by ingestion of the protein gliadin, a component of wheat gluten, and usually resolves on its withdrawal. Gliadin initiates mucosal damage which involves an immunological process in individuals with a genetic predisposition. However, the mechanism responsible for the small intestinal damage characteristic of celiac disease is still under debate. Small intestinal biopsy with the demonstration of a flat mucosa which is reversed on a gluten-free diet is considered the main approach for diagnosis of classical celiac disease. In addition, IgA antibodies against gliadin and endomysium, a structure of the smooth muscle connective tissue, are valuable tools for the detection of patients with celiac disease and for therapy control. Incidence rates of childhood celiac disease range from 1:300 in Western Ireland to 1:4700 in other European countries, and subclinical cases detected by serological screening revealed prevalences of 3.3 and 4 per 1000 in Italy and the USA, respectively. IgA antibodies to endomysium are particularly specific indicators of celiac disease, suggesting that this structure contains one or more target autoantigens that play a role in the pathogenesis of the disease. However, the identification of the endomysial autoantigen(s) has remained elusive. We identified tissue transglutaminase as the unknown endomysial autoantigen. Interestingly, gliadin is a preferred substrate for this enzyme, giving rise to novel antigenic epitopes.

Identification of tissue transglutaminase as the autoantigen of celiac disease

Background Celiac disease (CD) is an immune-mediated enteropathic condition triggered in genetically susceptible individuals by the ingestion of gluten. Although common in Europe, CD is thought to be rare in the United States, where there are no large epidemiologic studies of its prevalence. The aim of this study was to determine the prevalence of CD in at-risk and not-at-risk groups in the United States. Methods Serum antigliadin antibodies and anti–endomysial antibodies (EMA) were measured. In EMA-positive subjects, human tissue transglutaminase IgA antibodies and CD-associated human leukocyte antigen DQ2/DQ8 haplotypes were determined. Intestinal biopsy was recommended and performed whenever possible for all EMA-positive subjects. A total of 13 145 subjects were screened: 4508 first-degree and 1275 second-degree relatives of patients with biopsy-proven CD, 3236 symptomatic patients (with either gastrointestinal symptoms or a disorder associated with CD), and 4126 not-at-risk individuals. Results In at-risk groups, the prevalence of CD was 1:22 in first-degree relatives, 1:39 in second-degree relatives, and 1:56 in symptomatic patients. The overall prevalence of CD in not-at-risk groups was 1:133. All the EMA-positive subjects who underwent intestinal biopsy had lesions consistent with CD. Conclusions Our results suggest that CD occurs frequently not only in patients with gastrointestinal symptoms, but also in first- and second-degree relatives and patients with numerous common disorders even in the absence of gastrointestinal symptoms. The prevalence of CD in symptomatic patients and not-at-risk subjects was similar to that reported in Europe. Celiac disease appears to be a more common but neglected disorder than has generally been recognized in the United States.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/215079/ioi20641.pdf

Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: A large multicenter study

https://www.gastrojournal.org/article/S0016-5085(01)25187-7/pdf

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

American Gastroenterological Association (AGA) Institute Technical Review on the Diagnosis and Management of Celiac Disease

Introduction. Although the prevalence of celiac disease (CD) has been extensively investigated in recent years, an accurate estimate of CD frequency in the European population is still lacking. The...

/pdf/the-prevalence-of-celiac-disease-in-europe-results-of-a-10cw1ba84w.pdf

The prevalence of celiac disease in Europe: Results of a centralized, international mass screening project

Coeliac disease in the year 2000: exploring the iceberg

Antigliadin antibody screening for coeliac disease.

Treatment of Childhood Obesity by a Protein-Sparing Diet: A Clinical and Metabolic Study1

SIR,-The annotation on antibiotic treatment of suspected neonatal meningitis seems to demonstrate that optimal treatment of this thankfully rare disorder is still not clear.' The suggested array of antibiotic treatment and combined routes of administration may provide cover against a wide range of organisms, but is such treatment in the best interests of every patient? In a sick hypotensive infant who may already have compromised renal function the combination of aminoglycoside and cephalosporin may exacerbate the problem. To state that 'Gentamicin should be used primarily to treat the associated septicaemia' is rather puzzling, as the implication is that cephalosporins are incapable of doing this. Is there any evidence to suggest that cefotaxime is ineffective in the treatment of bacteraemia in neonates? I am concerned by the conviction of the authors in their management proposals. To begin a paragraph stating 'there is no doubt in our minds that intraventricular treatment should be used' and end it with 'there has been no study of intraventricular treatment... and little information on the ventricular drug concentration achieved after systemic treatment alone in dilated ventricles' is perhaps a little rash in view of the finding of significantly increased mortality after intraventricular treatment in the American study.2 The conclusion of McCracken and colleagues was that 'intraventricular therapy cannot be recommended for the routine management of neonatal meningitis caused by Gram negative enteric bacilli'. In the absence of a further randomised multicentre trial it is surely ill advised to recommend the adoption of this invasive and potentially dangerous mode of treatment as the standard treatment in neonatal Gram negative meningitis with ventricular dilatation.

https://adc.bmj.com/content/archdischild/65/7/810.2.full.pdf

When should the celiac patient have an intestinal biopsy.

132 antigliadin antibody coeliac disease screening in 5280 italian students aged 11–15 years

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