Intestinal anti-transglutaminase 2 immunoglobulin A deposits in children at risk for coeliac disease (CD): data from the PreventCD study.

In coeliac disease (CD), anti-tissue transglutaminase 2 immunoglobulin (Ig)A antibodies (anti-TG2) are produced and deposited in the intestine. PreventCD (www.preventcd.com) is a European multi-centre study, which investigates the influence of infant nutrition and that of genetic, immunological and other environmental factors on the risk of developing CD. The aim of the current study was to evaluate the appearance of intestinal anti-TG2 deposits in very early intestinal biopsies from at-risk infants and their predictive value for villous atrophy. Sixty-five small bowel biopsies, performed in 62 children, were investigated for the presence of intestinal anti-TG2 extracellular IgA deposits by using double immunofluorescence. The biopsies were performed in the presence of elevated serum levels of CD-associated antibodies and/or symptoms suggesting disease. Deposits of anti-TG2 IgA were present in 53 of 53 CD patients and three of three potential CD patients. In potential CD patients, mucosal deposits showed a patchy distribution characterized by some areas completely negative, whereas active CD patients had uniformly present and evident mucosal deposits. Only one of six patients without CD (negative for serum anti-TG2 and with normal mucosa) had intestinal deposits with a patchy distribution and a weak staining. Two of the 53 CD patients received a definitive diagnosis of CD after a second or third biopsy; mucosal deposits of anti-TG2 IgA were evaluated in all samples. Before developing villous atrophy, both patients had anti-TG2 deposits in normal mucosal architecture, antibodies in one patient being absent in serum. We demonstrated that in CD the intestinal deposits of anti-TG2 are a constant presence and appear very early in the natural history of disease.

Management guidelines of eosinophilic esophagitis in childhood.

OBJECTIVES: Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. With few exceptions, 15 eosinophils per high-power field (peak value) in ≥1 biopsy specimens are considered a minimum threshold for a diagnosis of EoE. The disease is restricted to the esophagus, and other causes of esophageal eosinophilia should be excluded, specifically proton pump inhibitor-responsive esophageal eosinophilia. This position paper aims at providing practical guidelines for the management of children and adolescents with EoE. METHODS: Relevant literature from searches of PubMed, CINAHL, and recent guidelines was reviewed. In the absence of an evidence base, recommendations reflect the expert opinion of the authors. Final consensus was obtained during 3 face-to-face meetings of the Gastroenterology Committee and 1 teleconference. RESULTS: The cornerstone of treatment is an elimination diet (targeted or empiric elimination diet, amino acid-based formula) and/or swallowed, topical corticosteroids. Systemic corticosteroids are reserved for severe symptoms requiring rapid relief or where other treatments have failed. Esophageal dilatation is an option in children with EoE who have esophageal stenosis unresponsive to drug therapy. Maintenance treatment may be required in case of frequent relapse, although an optimal regimen still needs to be determined. CONCLUSIONS: EoE is a chronic, relapsing inflammatory disease with largely unquantified long-term consequences. Investigations and treatment are tailored to the individual and must not create more morbidity for the patient and family than the disease itself. Better maintenance treatment as well as biomarkers for assessing treatment response and predicting long-term complications is urgently needed.

A practical guide for the diagnosis of primary enteric nervous system disorders.

OBJECTIVE: Primary gastrointestinal neuropathies are a heterogeneous group of enteric nervous system (ENS) disorders that continue to cause difficulties in diagnosis and histological interpretation. Recently, an international working group published guidelines for histological techniques and reporting, along with a classification of gastrointestinal neuromuscular pathology. The aim of this article was to review and summarize the key issues for pediatric gastroenterologists on the diagnostic workup of congenital ENS disorders. In addition, we provide further commentary on the continuing controversies in the field. RESULTS: Although the diagnostic criteria for Hirschsprung disease are well established, those for other forms of dysganglionosis remain ill-defined. Appropriate tissue sampling, handling, and expert interpretation are crucial to maximize diagnostic accuracy and reduce interobserver variability. The absence of validated age-related normal values for neuronal density, along with the lack of correlation between clinical and histological findings, result in significant diagnostic uncertainties while diagnosing quantitative aberrations such as hypoganglionosis or ultrashort Hirschsprung disease. Intestinal neuronal dysplasia remains a histological description of unclear significance. CONCLUSIONS: The evaluation of cellular quantitative or qualitative abnormalities of the ENS for clinical diagnosis remains complex. Such analysis should be carried out in laboratories that have the necessary expertise and access to their own validated reference values.

European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease.

OBJECTIVE: Diagnostic criteria for coeliac disease (CD) from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) were published in 1990. Since then, the autoantigen in CD, tissue transglutaminase, has been identified; the perception of CD has changed from that of a rather uncommon enteropathy to a common multiorgan disease strongly dependent on the haplotypes human leukocyte antigen (HLA)-DQ2 and HLA-DQ8; and CD-specific antibody tests have improved. METHODS: A panel of 17 experts defined CD and developed new diagnostic criteria based on the Delphi process. Two groups of patients were defined with different diagnostic approaches to diagnose CD: children with symptoms suggestive of CD (group 1) and asymptomatic children at increased risk for CD (group 2). The 2004 National Institutes of Health/Agency for Healthcare Research and Quality report and a systematic literature search on antibody tests for CD in paediatric patients covering the years 2004 to 2009 was the basis for the evidence-based recommendations on CD-specific antibody testing. RESULTS: In group 1, the diagnosis of CD is based on symptoms, positive serology, and histology that is consistent with CD. If immunoglobulin A anti-tissue transglutaminase type 2 antibody titers are high (>10 times the upper limit of normal), then the option is to diagnose CD without duodenal biopsies by applying a strict protocol with further laboratory tests. In group 2, the diagnosis of CD is based on positive serology and histology. HLA-DQ2 and HLA-DQ8 testing is valuable because CD is unlikely if both haplotypes are negative. CONCLUSIONS: The aim of the new guidelines was to achieve a high diagnostic accuracy and to reduce the burden for patients and their families. The performance of these guidelines in clinical practice should be evaluated prospectively.

Coeliac disease diagnosis: ESPGHAN 1990 criteria or need for a change? Results of a questionnaire.

BACKGROUND AND OBJECTIVES: A revision of criteria for diagnosing coeliac disease (CD) is being conducted by The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). In parallel, we have performed a survey aimed to evaluate present practices for CD among paediatric gastroenterologists and to learn their views on the need for modification of present criteria for CD diagnosis. PATIENTS AND METHODS: Questionnaires were distributed to experienced paediatric gastroenterologists (ESPGHAN members) via the Internet. RESULTS: Overall, 95 valid questionnaires were available for analysis, pertaining to 28 different countries, with the majority of responders treating patients with CD for >15 years. Only about 12% of the responders comply with present criteria, noncompliance being related mainly to the challenge policy. Approximately 90% request a revision and modification of the present criteria. Forty-four percent want to omit the small bowel biopsy in symptomatic children with positive anti-tissue transglutaminase immunoglobulin (Ig) A or endomysial IgA antibodies, especially if they are DQ2/DQ8 positive. For silent cases detected by screening with convincingly positive anti-tissue transglutaminase IgA or EMA IgA, about 30% consider that no small bowel biopsy should be required in selected cases. Adding human leukocyte antigen typing in the diagnostic workup was asked for by 42% of the responders. As for gluten challenge, a new policy is advocated restricting its obligation to cases whenever the diagnosis is doubtful or unclear. CONCLUSIONS: Based on these opinions, revision of the ESPGHAN criteria for diagnosing CD is urgently needed.

Diagnostic approach and management of cow's-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines.

OBJECTIVES: This guideline provides recommendations for the diagnosis and management of suspected cow's-milk protein allergy (CMPA) in Europe. It presents a practical approach with a diagnostic algorithm and is based on recently published evidence-based guidelines on CMPA. DIAGNOSIS: If CMPA is suspected by history and examination, then strict allergen avoidance is initiated. In certain circumstances (eg, a clear history of immediate symptoms, a life-threatening reaction with a positive test for CMP-specific IgE), the diagnosis can be made without a milk challenge. In all other circumstances, a controlled oral food challenge (open or blind) under medical supervision is required to confirm or exclude the diagnosis of CMPA. TREATMENT: In breast-fed infants, the mother should start a strict CMP-free diet. Non-breast-fed infants with confirmed CMPA should receive an extensively hydrolyzed protein-based formula with proven efficacy in appropriate clinical trials; amino acids-based formulae are reserved for certain situations. Soy protein formula, if tolerated, is an option beyond 6 months of age. Nutritional counseling and regular monitoring of growth are mandatory in all age groups requiring CMP exclusion. REEVALUATION: Patients should be reevaluated every 6 to 12 months to assess whether they have developed tolerance to CMP. This is achieved in >75% by 3 years of age and >90% by 6 years of age. Inappropriate or overly long dietary eliminations should be avoided. Such restrictions may impair the quality of life of both child and family, induce improper growth, and incur unnecessary health care costs.

Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.

OBJECTIVE: Our previous coeliac disease genome-wide association study (GWAS) implicated risk variants in the human leucocyte antigen (HLA) region and eight novel risk regions. To identify more coeliac disease loci, we selected 458 single nucleotide polymorphisms (SNPs) that showed more modest association in the GWAS for genotyping and analysis in four independent cohorts. DESIGN: 458 SNPs were assayed in 1682 cases and 3258 controls from three populations (UK, Irish and Dutch). We combined the results with the original GWAS cohort (767 UK cases and 1422 controls); six SNPs showed association with p<1 x 10(-04) and were then genotyped in an independent Italian coeliac cohort (538 cases and 593 controls). RESULTS: We identified two novel coeliac disease risk regions: 6q23.3 (OLIG3-TNFAIP3) and 2p16.1 (REL), both of which reached genome-wide significance in the combined analysis of all 2987 cases and 5273 controls (rs2327832 p = 1.3 x 10(-08), and rs842647 p = 5.2 x 10(-07)). We investigated the expression of these genes in the RNA isolated from biopsies and from whole blood RNA. We did not observe any changes in gene expression, nor in the correlation of genotype with gene expression. CONCLUSIONS: Both TNFAIP3 (A20, at the protein level) and REL are key mediators in the nuclear factor kappa B (NF-kappaB) inflammatory signalling pathway. For the first time, a role for primary heritable variation in this important biological pathway predisposing to coeliac disease has been identified. Currently, the HLA risk factors and the 10 established non-HLA risk factors explain approximately 40% of the heritability of coeliac disease.

A Simple Endoscopic Score Modified for the Upper Gastrointestinal Tract in Crohn's Disease [UGI-SES-CD]: A Report From the ImageKids Study.

OBJECTIVE: There is no standardized endoscopic description of upper gastrointestinal [UGI] disease in Crohn's disease [CD]. We prospectively applied the Simple Endoscopic Score for CD [SES-CD] to the UGI tract as a planned sub-study of the multicentre prospective ImageKids study. We aimed to assess the utility of the UGI-SES-CD and its clinical significance in paediatric CD. DESIGN: Patients underwent an oesophagogastroduodenoscopy [EGD], ileocolonoscopy, and magnetic resonance enterography [MRE] with explicit clinical data recorded. SES-CD was scored at each region [oesophagus, stomach body, antrum, and duodenum]. Half of the patients were followed for 18 months, when a repeat MRE was performed. RESULTS: A total of 202 children were included 56% males, mean age 11.5 ± 3.2 years, median weighted Paediatric Crohn's Disease Activity Index [wPCDAI 25]). UGI-SES-CD score ranged 0-17, with 95 [47%] having a UGI-SES-CD ≥1; no narrowing was detected. UGI-SES-CD ≥1 was associated with higher: wPCDAI [32.5 vs 20; p = 0.03]; Physician's Global Assessment [PGA] of inflammation (45 mm visual analogue score [VAS] vs 30 mm VAS; p = 0.04); ileocolonoscopic SES-CD [10 vs 7; p = 0.004], faecal calprotectin [717 µg/g vs 654 µ/g; p= 0.046]; and radiological global assessment of damage by MRE [7 mm VAS vs 0; p = 0.04]. In all, 81 patients were followed for 18 months and no association was identified between initial UGI SES-CD and markers of disease course such as surgery, MRE assessment, or treatment escalation. CONCLUSION: UGI-SES-CD is an easily reported objective scoring system and is associated with a more severe disease phenotype but not with disease course.

[Is it time for mass screening for celiac disease?]. / Is het tijd voor bevolkingsonderzoek naar coeliakie?

Celiac disease is a common condition with a variable presentation, and is frequently not recognized by the physician. Although a gluten-free diet has a positive effect on the health of the celiac patient, prevention would be even more beneficial. In this article we outline the different possibilities for primary and secondary prevention of celiac disease. Results of recent prospective studies show that at this moment primary prevention is not possible, but secondary preventive strategies can be applied to decrease the morbidity associated with this disease; mass screening is one option. Results of recent studies concerning this topic will be discussed.

Systematic review with meta-analysis: early infant feeding and coeliac disease--update 2015.

BACKGROUND: New evidence emerged on early feeding practices and the risk of coeliac disease. AIM: To systematically update evidence on these practices to find out whether there is a need to revise current recommendations. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched from July 2012 (end of last search) to February 2015 for studies of any design that assessed the effect of gluten consumption and breastfeeding on the development of coeliac disease and/or coeliac disease-related autoimmunity. RESULTS: We identified 21 publications, including two, new, large, randomised controlled trials performed in high-risk infants. Exclusive or any breastfeeding, as well as breastfeeding at the time of gluten introduction, did not reduce the risk of developing coeliac disease during childhood. For infants at high risk of developing coeliac disease, gluten introduction at 4 months of age in very small amounts, or at 6 or 12 months of age, resulted in similar rates of coeliac disease diagnosis in early childhood. Later gluten introduction was associated with later development of coeliac specific autoimmunity and coeliac disease during childhood, but not total risk reduction. Observational studies indicate that consumption of a higher amount of gluten at weaning may increase the risk for coeliac disease development. CONCLUSIONS: Infant feeding practices (breastfeeding, time of gluten introduction) have no effect on the risk of developing coeliac disease during childhood (at least at specific timeframes evaluated in the included studies), necessitating an update of current European recommendations.

Long-term morphological and immunohistochemical observations on biopsy specimens of small intestine from children with gluten-sensitive enteropathy.

Jejunal biopsy specimens from nine Spanish children with gluten-sensitive enteropathy were studied with morphometric and immunohistochemical techniques in three stages of the diseases: the first biopsy was taken for diagnosis, when the child had a gluten-containing diet, the second after gluten withdrawal, and the third biopsy after gluten-provocation. The findings were compared with those in 10 healthy adults. The villous:crypt ratio and the length of the surface epithelium per stretched millimetre muscularis mucosae were decreased, whereas the number of interepithelial lymphocytes per millimetre surface epithelium was increased when the child had a gluten-containing diet. Although these parameters improved after withdrawal of gluten for at least seven months, they never reached the values of the healthy control group. With the indirect immunoperoxidase technique it was shown that the numbers of IgA-, IgG-, and IgM-containing cells, expressed per "mucosal tissue unit" of 4 micrometer thick and 1 mm wide, were significantly increased during the active phases of the disease. This increase was most striking for the IgM-containing cells. The most sensitive parameters for the histological diagnosis of gluten-sensitive enteropathy are the villous:crypt ratio or the length of the surface epithelium per millimetre muscularis mucosae, the number of interepithelial lymphocytes per millimetre surface epithelium, and the number of IgM-containing cells per millimetre muscularis mucosae.

Juvenile chronic arthritis and coeliac disease in The Netherlands.

OBJECTIVE: It has been suggested that juvenile chronic arthritis (JCA) is associated with coeliac disease in a frequency of 0.4-2%. In order to investigate the frequency of coeliac disease in cases of JCA and the possibility of underdiagnosis in our area, we screened 62 children with JCA (mean age 9.8 +/- 3.5 year) for coeliac disease. METHODS: All children were screened for coeliac disease by measuring the IgA-class of antigliadin, antireticulin and antiendomysium antibodies in serum and by measuring intestinal permeability by a sugar absorption test using lactulose and mannitol. In cases of at least one positive test, a small-bowel biopsy for diagnosis of coeliac disease was offered. RESULTS: Of the 62 children with JCA, 8 had an abnormal screening result and were suspected of having coeliac disease. In four of the five children in whom a small-bowel biopsy was performed, the intestinal mucosa was normal and in one child villous atrophy characteristic of coeliac disease was found. Therefore, the prevalence of coeliac disease in our study group was 1.5%, which is in agreement with the literature. CONCLUSION: These findings indicate no underdiagnosis of coeliac disease in JCA in our area.

Eating habits of young children with Down syndrome in The Netherlands: adequate nutrient intakes but delayed introduction of solid food.

OBJECTIVES: To investigate nutritional status, pattern of being breast-fed, age at introduction of solid food, and adequacy of energy and nutrient intakes in children with Down syndrome in The Netherlands. DESIGN: Nutritional status was assessed by height and weight measurements. The dietary history method was used to collect information on the diet. Data obtained from children with Down syndrome were compared with data from control subjects and from the general population of Dutch children. Adequacy of energy and nutrient intakes was assessed by comparison to US recommendations. SUBJECTS: Forty-four Dutch children with Down syndrome (newborns to 4-year-olds) and 37 healthy control subjects without this syndrome. STATISTICAL ANALYSES: The prevalence of breast-feeding of children with and without Down syndrome was compared using the chi 2 test. To compare ages at which solid food was introduced, the log-rank test and Kaplan-Meier curves were used. Anthropometric data and mean dietary intake were compared between the groups using 2-way analysis of variance. Comparison to recommended levels of dietary intake was performed using 95% confidence intervals. RESULTS: Heights and weights of the children with Down syndrome were in the normal range. Down syndrome does not affect the prevalence of breast-feeding of children or the adequacy of their energy and nutrient intakes, but it does significantly delay the age at which solid food is introduced, which can be deleterious to oral-motor development. APPLICATION: If late introduction of solid food is observed in children with Down syndrome, pre-speech therapy should be considered.

Screening for coeliac disease in Dutch children with associated diseases.

Our objective was to assess the frequency of coeliac disease in children with associated disorders in the province of "Zuid-Holland". The Netherlands. We therefore screened 115 children with Down's syndrome, 62 children with juvenile rheumatoid arthritis (JRA) and 46 children with diabetes mellitus for CD using the IgA-class of antigliadin, antiendomysium and antireticulin antibodies in serum, and a functional sugar absorption test. The antiendomysium antibody test was the screening test that performed the best. Every patient who has at least one positive test underwent a jejunal biopsy for the diagnosis of CD. No association could be demonstrated between CD and diabetes mellitus. The frequency of CD in Down's syndrome was 7.0%, which is much higher than that found from screening the general population. CD was found in one child with JRA (1.5%), who also had Down's syndrome. We recommend screening for CD in all persons with Down's syndrome using at least the antiendomysium antibody test.

[Diagnosis of celiac disease in children; guidelines for pediatric gastroenterologists. Section of Pediatric Gastroenterology, Dutch Society of Pediatrics]. / Diagnostiek van coeliakie bij kinderen; richtlijnen van kindergastro-enterologen.

For the diagnosis of coeliac disease (CD) to be made in children and for the prescription of a gluten-free diet, clear histological changes in the small bowel biopsy sample have to be found. Serological testing for antibodies against endomysium and gliadin has only a preliminary significance. In children with strong clinical suspicion of CD, histological investigation of a small bowel biopsy should be performed independently of the results of serological screening (endomysium and gliadin antibodies). In children with less clear clinical suspicion of CD, serological screening may be used to select those who need investigation of small bowel histology. The number of small bowel biopsies that should be performed has been changed. In children < 2 years with clinical symptoms and small bowel villous atrophy, CD is confirmed when symptoms and atrophy significantly improve during gluten-free diet, while small bowel histology significantly deteriorates during gluten challenge. In children > 2 years with clinical symptoms combined with abnormal serology and villous atrophy, CD is confirmed when during gluten-free diet the symptoms disappear and serology improves. In case of family screening, diseases associated with CD or Down's syndrome, CD is confirmed when symptoms (if any), and previous abnormal serology and small bowel histology significantly improve during gluten-free diet.

[Gluten as food additive in The Netherlands: cheese forbidden for celiac patients?]. / Gluten als voedingsadditivum in Nederland: kaas verboden voor coeliakiepatiënten?

A new coating for cheese, to be introduced in May, consists entirely of natural degradable components. The coating is based on wheat gluten. This increase in the amount of gluten in the Dutch diet may lead to overt coeliac disease in people with a subclinical form of it, and will limit the dietary choices of patients already suffering from the disease.

[Symptoms of disease and food allergy in children with Down syndrome]. / Gezondheidsklachten en voedselallergie bij kinderen met het syndroom van Down.

OBJECTIVE: To obtain an impression of how often parents of children with Down's syndrome suspect their children of having a food allergy and what action results from this suspicion. DESIGN: Inventorizing controlled descriptive study. 'Zuid-Holland' in the Netherlands. METHODS: An anonymous questionnaire was sent to 110 parents of children with Down's syndrome and 223 control parents. RESULTS: The parents of children with Down's syndrome reported symptoms of their child which might relate to food allergy more frequently than control parents. They reported more respiratory disease symptoms (62% and 53% respectively; pneumonia: 22% and 3%), more gastrointestinal disease symptoms (28% and 17%; constipation or diarrhoea: 28% and 13%), but fewer skin disease symptoms (12% and 26%). 34% of the parents of Down's syndrome children and 22% of the control parents suspected their child of having an allergy and 13% in both groups suspected food to be the allergenic responsible. Medical and laboratory investigations were performed in 37% and 31% and food allergy was diagnosed in 7% and 31% respectively. No elimination-reïntroduction diet was reported as used for diagnosing. Parents of children with Down's syndrome were less satisfied with their consultation of health workers. All parents in both groups who suspected their children of having a food allergy started an elimination diet, 66% found it had a beneficial effect. CONCLUSION: Compared with control parents, parents of children with Down's syndrome reported symptoms relating to food allergy more frequently, suspected their children of having a food allergy equally often, but had it diagnosed less frequently. However, neither group of parents mentioned that an elimination-provocation test was used for the diagnosis.

[Twenty years of childhood coeliac disease in the Netherlands: more diagnoses and a changed clinical picture]. / Twintig jaar coeliakie bij kinderen in Nederland: meer diagnosen en een veranderde verschijningsvorm.

OBJECTIVE: To assess the incidence of childhood coeliac disease in the Netherlands and to study the clinical features. DESIGN: Prospective. SETTING: Leiden University Medical Centre, Leiden, the Netherlands. METHOD: Cases of childhood coeliac disease in the Netherlands in 1993-1995 were identified by means of the Dutch Paediatric Surveillance Unit. Inclusion criteria were: birth in the Netherlands, diagnosis with at least one small bowel biopsy in 1993-1995 and age at diagnosis 0-14 years. The data were cross checked with the Dutch Network and National Database of Pathology and compared with data from a previous study on childhood coeliac disease, 1975-1990. RESULTS: 297 Coeliac patients were identified by means of the Surveillance Unit, another 32 through the National Database of Pathology. The mean crude incidence rate of diagnosed childhood coeliac disease was 0.51/1000 live births, which was in the range of rates found in other West European countries and significantly higher than the mean crude incidence rate of 0.18/1000 live births found in the Netherlands in 1975-1990. The clinical presentation was classic up to 1990: chronic diarrhoea, abdominal distention and growth failure. From 1993 onward, however, the number of children with chronic diarrhoea and abdominal distention decreased significantly and the number with weight loss, anaemia and abdominal pain increased. Associated disorders were present in 13.7% of the cases. CONCLUSIONS: The incidence of diagnosed childhood coeliac disease in the Netherlands showed a tendency to increase significantly during the past decade. In a period of 20 years a significant trend toward change in the clinical presentation of coeliac disease in Dutch children was observed.

[The clinical significance of anti-gliadin antibodies determination in blood of children with suspected celiac diseases]. / De klinische waarde van de bepaling van anti-gliadine antilichamen in het serum van kinderen met verdenking van coeliakie.

Screening tests for coeliac disease may be useful to select the patients who should undergo a small intestine biopsy. It has been reported that the determination of serum levels of anti-gliadin antibodies is a good screening method for small intestine damage in coeliac disease. We have retrospectively assessed the value of the anti-gliadin antibody test in detecting villous atrophy of the small bowel. Antigliadin antibodies were measured with an ELISA technique in sera of 44 children seen at the Department of Paediatrics, Leiden University Hospital, who underwent 53 small intestine biopsies because of suspected coeliac disease. The relation between the histopathological findings of the small intestine and the results of the anti-gliadin antibody quantifications in serum were studied. In 9 of the 10 children with villous atrophy high Ig total and IgG-titers were found. Five children with villous atrophy, 2 of them with a selective IgA-deficiency, had normal IgA-AGA titers in serum. 17 Children with normal biopsies had high Ig total and IgG-AGA titers, but no child with normal small intestine biopsy had high IgA-AGA titers in serum. We conclude that the determination of anti-gliadin antibodies as screening for mucosal damage must be based on the measurement of antibodies within the IgG as well as the IgA class.