The effects of oats on the function of gut microflora in children with coeliac disease.

BACKGROUND: Faecal short chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported high faecal SCFA levels in children with coeliac disease (CD), indicating alteration in gut microfloral metabolism. Data accumulated over recent decades by us and others suggest that wheat-free oats can safely be included in a gluten-free diet (GFD). However, concerns have been raised with respect to the safety of oats in a subset of coeliacs. AIM: To describe faecal SCFA patterns in children with newly diagnosed CD treated for 1 year with a GFD with or without oats. METHODS: This report is part of a randomised, double-blind study on the effect of a GFD containing oats (GFD-oats) vs. a standard GFD (GFD-std). Faecal samples were received from 34 children in the GFD-oats group and 37 in the GFD-std group at initial diagnosis and/or after 1 year on a GFD. Faecal SCFAs were analysed. RESULTS: The GFD-std group had a significantly lower total faecal SCFA concentration at 12 months compared with 0 months (P < 0.05). In contrast, total SCFA in the GFD-oats group remained high after 1 year on the GFD. The children in the GFD-oats group had significantly higher acetic acid (P < 0.05), n-butyric acid (P < 0.05) and total SCFA concentration (P < 0.01) after 1-year diet treatment compared to the GFD-std group. CONCLUSIONS: Our results indicate that oats do affect the gut microflora function, and that some coeliac children receiving oats may develop gut mucosal inflammation, that may present a risk for future complications.

Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes.

Up-regulation of interleukin (IL)-17 in small intestinal mucosa has been reported in coeliac disease (CD) and in peripheral blood in type 1 diabetes (T1D). We explored mucosal IL-17 immunity in different stages of CD, including transglutaminase antibody (TGA)-positive children with potential CD, children with untreated and gluten-free diet-treated CD and in children with T1D. Immunohistochemistry was used for identification of IL-17 and forkhead box protein 3 (FoxP3)-positive cells and quantitative polymerase chain reaction (qPCR) for IL-17, FoxP3, retinoic acid-related orphan receptor (ROR)c and interferon (IFN)-γ transcripts. IL-1ß, IL-6 and IL-17 were studied in supernatants from biopsy cultures. Expression of the apoptotic markers BAX and bcl-2 was evaluated in IL-17-stimulated CaCo-2 cells. The mucosal expression of IL-17 and FoxP3 transcripts were elevated in individuals with untreated CD when compared with the TGA-negative reference children, children with potential CD or gluten-free diet-treated children with CD (P < 0·005 for all IL-17 comparisons and P < 0·01 for all FoxP3 comparisons). The numbers of IL-17-positive cells were higher in lamina propria in children with CD than in children with T1D (P < 0·05). In biopsy specimens from patients with untreated CD, enhanced spontaneous secretion of IL-1ß, IL-6 and IL-17 was seen. Activation of anti-apoptotic bcl-2 in IL-17-treated CaCo-2 epithelial cells suggests that IL-17 might be involved in mucosal protection. Up-regulation of IL-17 could, however, serve as a biomarker for the development of villous atrophy and active CD.

Children with screening-detected coeliac disease show increased levels of nitric oxide products in urine.

AIM: Increased concentration of nitric oxide (NO) metabolites, nitrite and nitrate, in the urine is a strong indication of ongoing small intestinal inflammation, which is a hallmark of the enteropathy of coeliac disease (CD). It has previously been shown that children with symptomatic, untreated CD have increased levels of NO oxidation products in their urine. The aim of this study was to investigate whether screening-detected, asymptomatic coeliac children display the same urinary nitrite/nitrate pattern. METHODS: In a multicenter screening study, serum samples were collected from 7208 12-year-old children without previously diagnosed CD. Sera were analysed for anti-human tissue transglutaminase (tTG) of isotype IgA. Small bowel biopsy was performed in antibody-positive children, yielding 153 new cases of CD. In the screening-detected individuals, the sum of nitrite and nitrate concentrations in the urine was analysed and used as an indicator of NO production. For comparison, 73 children with untreated, symptomatic CD were studied. RESULTS: The nitrite/nitrate levels in children with screening-detected CD and those with untreated symptomatic CD did not differ significantly. Both groups had significantly increased urinary nitrite/nitrate concentrations compared to the children with normal small bowel biopsy (p < 0.001). CONCLUSION: Children with screening-detected CD have increased production of NO just as children with untreated symptomatic CD. High NO metabolite levels in the urine may indicate a pathogenetic feature of CD and be a marker of major clinical importance.

Are children from Crete abandoning a Mediterranean diet?

INTRODUCTION: Mediterranean countries such as Greece have experienced rapid social change in the last decade. These community changes affect nutritional habits and there is a tendency for the traditional healthy Mediterranean diet to be abandoned. METHODS: The parents of children from one rural Greek village on Crete (Neapolis), and one rural village in Sweden (Kisa) were invited to their primary health care centers for an interview and to fill in a validated nutrition questionnaire, KidMed. RESULTS: There were no differences (p = 0.48) in total KidMed score between the Cretan and Swedish children, adjusted for gender and age. However, there were some significant differences in scores on certain KidMed questions. Parents of the Cretan children reported significantly higher daily use of olive oil at home and more regular nut consumption, but also more commercially baked goods or pastries for breakfast. The parents of Swedish children reported significantly higher use of cereals, grains or bread for breakfast. The mean BMIs were similar for the Cretan (Neapolis mean 16.8, 95% CI 13.5-23.0) and for the Swedish children (Kisa mean 17.4, 95% CI 13.7-25.5) CONCLUSION: The results suggest the possibility of changing nutritional habits, measurable among young children in rural areas. The study raises the question of whether Cretan children may have abandoned some aspects of the traditional Mediterranean diet. It may also be that Swedish children have changed their diet in favor of a more Mediterranean food choice. The major limitation of the study is the small sample size, and further, larger studies are warranted.

IgA endomysium antibodies--an early predictor for celiac disease in children without villous atrophy.

AIM: To evaluate possible differences between children with anti-endomysium antibodies (EMA) positivity and normal small bowel mucosa and children with positive EMA and an enteropathy diagnosed as celiac disease (CD). METHODS: Children with suspected CD and positive EMA (>or=1/10) undergoing small bowel biopsy during 1996 to 2002, were investigated (n=133). Data registered were: year and month of birth, timing of the first biopsy, sex, heredity for CD, dermatitis herpetiformis and diabetes mellitus and outcome of the anti-gliadin antibody test (AGA). The case group, with EMA positivity and normal histology (n=39; 59% female, mean age at the first biopsy 7.3 years, range 1.4-16), was compared with the disease control group, with positive EMA and a biopsy suggestive and further on diagnosed as CD (n=94; 56% female; mean age 7.6 years at the first biopsy, range 0.70-17). RESULTS: AGA positivity and heredity for CD were found to predict the outcome of a pathological jejunal mucosa. Nineteen of the 39 children in the case group were rebiopsied of whom 11 had developed an enteropathy during a follow-up period of 2-7 years (median 4.5 years). CONCLUSIONS: EMA positivity in the absence of small bowel enteropathy could be a very early predictor for later overt CD, and necessitates further follow-up, especially if the child is AGA positive and there is a family history of CD.

Combinations of common chronic paediatric diseases deviate the immune response in diverging directions.

The cytokine pattern of T lymphocytes has not been characterized in children with combinations of paediatric immunological disorders. We describe cytokine secretion in children with type 1 diabetes, coeliac disease and allergy and combinations of two of these diseases after stimulation with 'disease-specific' antigens. Peripheral blood mononuclear cells (PBMC) were collected from 68 children with type 1 diabetes, allergy or coeliac disease, two of these diseases in combination or none of these diseases. Using the enzyme-linked immunospot (ELISPOT) technique, interferon (IFN)-gamma and interleukin (IL)-4 were analysed from fresh PBMC spontaneously and after in vitro stimulation with antigens associated with one or more of these diseases (insulin, gluten, birch and cat extract, beta-lactoglobulin, ovalbumin and phytohaemagglutinin) in order to divide T helper (Th)1- from Th2-like lymphocytes. Stimulation with birch and cat extract caused increased IL-4 secretion in allergic children. A low IFN-gamma response to insulin was found in type 1 diabetic children, whereas allergic children responded to insulin by increased IL-4 secretion. Children suffering from both type 1 diabetes (Th1-prone) and allergy (Th2-prone) reacted distinctly to general mitogen stimulation. Children suffering from two Th1-dominated diseases (type 1 diabetes and coeliac disease) showed hardly any response to either food or inhalation allergens. Our results indicate an important interplay between common immunological diseases in children. The combination of two Th1-deviated diseases is associated with a suppressed immune response, whereas a combination of Th1- and Th2-dominated diseases appears to increase the general immune response.

Radiation risk and cost-benefit analysis of a paediatric radiology procedure: results from a national study.

A national study was performed to investigate radiation doses and associated risks to patients during X-ray fluoroscopy-guided small intestinal biopsies in the investigation of coeliac disease. Thermoluminescent dosemeters (TLD) and questionnaires were sent to 42 of the 43 paediatric departments in Sweden performing these biopsies. During the study period (2 x 3 weeks) 257 biopsies were recorded, representing about 10% of annually performed paediatric investigations. The results show that the absorbed dose during biopsy ranged from 0.04 mGy to 23.8 mGy (mean 1.87 mGy). The fluoroscopy time ranged from 2 s to 663 s (mean 60 s). The collective dose from the procedure amounts to 4.7 manSv year(-1). Thus, the annual excess cancer mortality, including severe hereditary effects, can be estimated at 0.6-0.7 cases per year. However, significant dose saving can be obtained by proper choice of sedation and biopsy equipment.

Gut microflora associated characteristics in children with celiac disease.

OBJECTIVES: The aim of the study was to investigate the metabolic function of intestinal microflora in children with celiac disease (CD) in order to find out if there is a deviant gut flora in CD patients compared to healthy controls. METHODS: The study group comprised children with CD, consecutively diagnosed according to current criteria given by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition. Thirty-six children were studied at presentation, i.e., on a normal gluten-containing diet, with clinical symptoms and signs indicative of CD, positive celiac serology markers, and a small bowel biopsy showing severe enteropathy. Forty-seven patients were studied when they had been on a gluten-free diet (GFD) for at least 3 months. For comparison, a group of 42 healthy controls (HC) were studied. The functional status of the intestinal microflora was evaluated by gas-liquid chromatography of short chain fatty acids (SCFAs) in fecal samples. RESULTS: There was a significant difference between untreated CD children and HC as well as between treated CD children and HC regarding acetic, i-butyric, i-valeric acid, and total SCFAs. The propionic and n-valeric acids differed significantly between CD children on GFD and HC. Moreover, there was a strong correlation between i-butyric and i-valeric acids in all study groups. CONCLUSIONS: This is the first study of the SCFA pattern in fecal samples from children with CD. The results indicate that there is a difference in the metabolic activity of intestinal microbial flora in children with CD compared to that in HC. The finding of a different pattern of some SCFAs in celiacs both at presentation and during treatment with GFD indicates that it is a genuine phenomenon of CD not affected by either the diet, the inflammation, or the autoimmune status of the patient.

Increasing prevalence of coeliac disease in Swedish children: influence of feeding recommendations, serological screening and small intestinal biopsy activity.

BACKGROUND: The prevalence of coeliac disease (CD) in Swedish children has attracted considerable interest over the past few decades, and especially the influence of feeding habits on the increased incidence. A national study has reported a trend towards a decrease in incidence after a change in infant feeding recommendations was introduced in 1996. The aim of this study was to evaluate, in a geographically defined area, the change in incidence with time and the influence of the introduction of antibody analysis. METHODS: Cases of suspected paediatric CD between 1980 and 2003 were studied for prevalence, biopsy findings and antibody analyses. RESULTS: A total of 2029 children were investigated by small intestinal biopsy, yielding 554 CD cases. The area initially showed the same trend as the national study, but the annual incidence rate is now increasing again. Median age at diagnosis has increased significantly since 1997 from less than 2 years of age to above 5 years. Cumulative incidence at 2 years of age is much higher for the birth cohorts 1983-96 than 1980-82 or 1997-2001. Diagnostic accuracy was significantly higher after the introduction of antigliadin (AGA) analysis, and especially after antiendomysium (EMA) analysis. CONCLUSIONS: The incidence rate of CD in small children in our region has varied widely over the 24-year period observed. Feeding practice and methods of investigation have changed during this period. The annual incidence rate for the total child population in 2003 was almost equal to the peak value observed in 1994. There were no conclusive results on whether antibody analysis had an influence on diagnostic activity, but this seems to have increased diagnostic accuracy.

Oats to children with newly diagnosed coeliac disease: a randomised double blind study.

BACKGROUND: Treatment of coeliac disease (CD) requires lifelong adherence to a strict gluten free diet (GFD) which hitherto has consisted of a diet free of wheat, rye, barley, and oats. Recent studies, mainly in adults, have shown that oats are non-toxic to CD patients. In children, only open studies comprising a small number of patients have been performed. AIM: To determine if children with CD tolerate oats in their GFD. PATIENTS AND METHODS: In this double blind multicentre study involving eight paediatric clinics, 116 children with newly diagnosed CD were randomised to one of two groups: one group was given a standard GFD (GFD-std) and one group was given a GFD with additional wheat free oat products (GFD-oats). The study period was one year. Small bowel biopsy was performed at the beginning and end of the study. Serum IgA antigliadin, antiendomysium, and antitissue transglutaminase antibodies were monitored at 0, 3, 6, and 12 months. RESULTS: Ninety three patients completed the study. Median (range) daily oat intake in the GFD-oats group (n = 42) was 15 (5-40) g at the six month control and 15 (0-43) g at the end of the study. All patients were in clinical remission after the study period. The GFD-oats and GFD-std groups did not differ significantly at the end of the study regarding coeliac serology markers or small bowel mucosal architecture, including numbers of intraepithelial lymphocytes. Significantly more children in the youngest age group withdrew. CONCLUSIONS: This is the first randomised double blind study showing that the addition of moderate amounts of oats to a GFD does not prevent clinical or small bowel mucosal healing, or humoral immunological downregulation in coeliac children. This is in accordance with the findings of studies in adult coeliacs and indicates that oats, added to the otherwise GFD, can be accepted and tolerated by the majority of children with CD.

Antibodies to oat prolamines (avenins) in children with coeliac disease.

BACKGROUND: The use of oats in a gluten-free diet for children with coeliac disease is presently under investigation. In this study we measured the content of antibodies to oat prolamines (avenin) in sera from coeliac children and reference children. METHODS: Crude avenin was prepared by extraction with ethanol and salt-solution and used as antigen in a three-step ELISA. Sera from 81 children, including 34 children with verified coeliac disease, were analysed for both IgA and IgG antibodies to avenin and gliadin. Sera were also incubated with gliadin before exposure to avenin, and vice versa, to assess a possible cross-reaction between the species. Keyhole limpet hemocyanin (KLH) was used as a negative control. RESULTS: Children with coeliac disease on a normal diet had significantly higher levels of antibodies to avenin, both IgG and IgA, than reference children (P < 0.001) and the levels correlated positively with gliadin antibodies, especially of IgA-type (r = 0.798). Both anti-avenin and anti-gliadin antibodies were only absorbed by the corresponding protein. CONCLUSIONS: Children with coeliac disease have antibodies to oat proteins at significantly higher levels than reference children. The absorption test did not indicate a cross-reactivity between the prolamines of wheat and oats. The method will be employed for repeated sampling of anti-avenin antibodies during a prospective interventional study with a gluten-free diet supplemented with oats.

Conscious or deep sedation: a questionnaire regarding the experience of parents, children and staff during small bowel biopsy.

AIM: The paediatric clinics of Linköping and Norrköping, Sweden, have different procedures regarding premedication and sedation during small bowel biopsy in children with suspected or diagnosed coeliac disease. In Linköping deep sedation using intravenous propofol is the method of sedation being used and parents are not present during the biopsy procedure. In Norrköping conscious sedation using intravenous midazolam is the routine and parents stay with their child throughout the whole biopsy procedure. The aim of this study was to find out whether the preprocedural and procedural differences between the clinics affected the way in which the parents and children experienced the time before and during the biopsy procedure. METHODS: A questionnaire was used to ask the parents of 102 children who had undergone small bowel capsule biopsy for their opinion regarding the discomfort experienced by their children. The parents' and children's experience was also compared with that of the paediatric nurse caring for the family during the biopsy procedure, and the paediatric gastroenterologist performing the biopsy. RESULTS: The differences regarding premedication and sedation between the two groups did not seem to affect the parents' or the children's total experience of the biopsy procedure, nor did the presence or absence of the parents throughout the biopsy procedure. As regards the sedation given, 95% of the parents did not think that their children suffered any discomfort at all. The total experience of the biopsy procedure on a five-grade scale (5 being very good, 1 being very bad) was 5 for the parents and 4 for the children in both centres. Parents and children in both centres were very satisfied with the way in which they were taken care of during their visit to the hospital. In both units there was an obvious correlation between how the paediatric nurse experienced the biopsy procedure and how the paediatric gastroenterologist did, but only a weak correlation between the experience of the parents and that of the paediatric gastroenterologist and paediatric nurse. The anxiety of the parents was similarly estimated by the paediatric gastroenterologist and the paediatric nurse in both centres. There was no correlation between their assessment and the experience reported by the parents. CONCLUSION: The children undergoing small bowel biopsy and their parents felt well taken care of during their visit to the two hospitals. The differences between the clinics regarding method of sedation and presence or absence of the parents did not seem to affect how the parents and children experienced the biopsy procedure.

Increase in nitric oxide urinary products during gluten challenge in children with coeliac disease.

BACKGROUND: Coeliac disease is a gluten-sensitive enteropathy where pro-inflammatory cytokines and excess nitric oxide (NO) production can contribute to mucosal damage. NO urinary products are elevated in coeliac children on a gluten diet, but it is not known how rapidly this increase develops after gluten exposure. METHODS: Oral gluten challenge was performed in 25 children whose families kept a daily record of gluten intake and symptoms. Blood was analysed monthly for antigliadin (AGA) and endomysium antibodies (EMA). Urine was analysed every second week for NO products, i.e. the sum of nitrite and nitrate was measured with a colorimetric method. We performed a third biopsy when clinical symptoms indicated a relapse. Median age at the post-challenge biopsy was 3.8 (2.7-8.8) years. RESULTS: Signs of morphological or serological relapse were seen in all children. Mean daily gluten intake was 0.10 (range 0.02-0.26) g/kg bodyweight. Median NO level was doubled and significantly higher after 4 weeks of challenge but not after 2 weeks. EMA, but not AGA levels, correlated positively with NO. Intraepithelial lymphocyte count was significantly higher in the post-challenge biopsy, but did not correlate with the NO levels. CONCLUSIONS: NO products in urine increased during gluten challenge. EMA levels reflected severity of mucosal damage, and NO products reflected the inflammatory response, which was doubled after 4 weeks of challenge. The NO analysis is simple and non-traumatic for the child. It can be performed repeatedly during investigation of children with suspected coeliac disease.

Familial prevalence of coeliac disease: a twenty-year follow-up study.

BACKGROUND: The genetic predisposition of coeliac disease (CD) is well known. Previous studies of first-degree relatives of coeliac patients have shown that as many as 10% have the disease. In 1981, we published a study in which all first-degree relatives of 32 index patients with CD were investigated by small-bowel biopsy. We found 2 relatives (2%) with CD. The present study is a re-investigation of all first-degree relatives of the same index patients performed 20-25 years after the first study to reveal any new cases of CD in this high-risk population. METHODS: All 120 first-degree relatives were screened for CD by means of serological markers of CD. The relatives with positive markers were submitted to small-bowel biopsy. RESULTS: Eight new cases of CD were found among the relatives. Two had been investigated by small-bowel biopsy 20 years previously, when they had only minor mucosal changes not classified as CD. The other six new cases of CD were found among offspring of the index patients and were born after completion of the previous study. Thus no new case of CD was found among those relatives who had a completely normal small-bowel biopsy 20-25 years previously. CONCLUSIONS: The high prevalence of CD among first-degree relatives of coeliac patients (8.3% in this study) supports the need to screen for CD in this high-risk population. Even relatives with only mild enteropathy should be followed carefully, since some may subsequently develop CD.

Variation in the CTLA4/CD28 gene region confers an increased risk of coeliac disease.

Susceptibility to coeliac disease involves HLA and non-HLA-linked genes. The CTLA4/CD28 gene region encodes immune regulatory T-cell surface molecules and is a strong candidate as a susceptibility locus. We evaluated CTLA4/CD28 in coeliac disease by genetic linkage and association and combined our findings with published studies through a meta-analysis. 116 multiplex families were genotyped across CTLA4/CD28 using eight markers. The contribution of CTLA4/CD28 to coeliac disease was assessed by non-parametric linkage and association analyses. Seven studies were identified that had evaluated the relationship between CTLA4/CD28 and coeliac disease and a pooled analysis of data undertaken. In our study there was evidence for a relationship between variation in the CTLA4/CD28 region and coeliac disease by linkage and association analyses. However, the findings did not attain formal statistical significance (p = 0.004 and 0.039, respectively). Pooling findings with published results showed significant evidence for linkage (504 families) and association (940 families): p values, 0.0001 and 0.0014 at D2S2214, respectively, and 0.0008 and 0.0006 at D2S116, respectively. These findings suggest that variation in the CD28/CTLA4 gene region is a determinant of coeliac disease susceptibility. Dissecting the sequence variation underlying this relationship will depend on further analyses utilising denser sets of markers.

Skin prick test in duplicate: is it necessary?

BACKGROUND: Duplicate skin prick testing has previously been recommended because of reports that accidental negative tests are common. However, duplicate tests also mean an extra allergen load, which may increase the risk of inducing a generalized reaction at the test situation, at least in the youngest infants. OBJECTIVE: To investigate whether the occurrence of both a positive and negative test result is a common feature when performing duplicate skin prick tests and can therefore justify the duplicate method. METHODS: A retrospective analysis of all skin prick tests performed in duplicate at the pediatric clinic at University Hospital in Linköping, Sweden, in 1997. RESULTS: Of 1,087 skin prick tests, 14 resulted in one positive and one negative test, or 1.3%. The corresponding figure in the youngest age group, (ie, <2 years of age) was 3 of 340 (0.9%). CONCLUSIONS: Considering the risk of inducing a summation of the reactions, and thereby a generalized allergic reaction, when applying an extra allergen load on the limited surface of the small arm, we conclude that the results of this study justify using single prick test, at least in the youngest age group and probably when testing children of all ages.

New automated immunoassay measuring immunoglobulin A antigliadin antibodies for prediction of celiac disease in childhood.

The prevalence of celiac disease (CD) in Sweden is about 4 cases per 1,000 people. Screening for CD with serological tests indicates similar high prevalences in many other countries. Between 1 November 1992 and 30 April 1995, 133 children (9 months to 16.7 years of age) with suspected CD were studied. The predictive value (PV) of immunoglobulin A antigliadin antibodies (IgA-AGA) in the serum as assayed with two new commercial automated immunoassays--the Pharmacia CAP System Gliadin IgA FEIA (CAP) and the UNICAP-100 (UNICAP)--and with three "in-house" methods was evaluated using assessment of the small intestinal mucosa morphology as the "gold standard." All serum samples were analyzed for total serum IgA. At presentation the diagnostic sensitivities and specificities of the different tests varied from 0.72 to 0.88 and 0.67 to 0.87, respectively. All methods showed a higher sensitivity for CD in younger children. The area under each assay's receiver operating characteristic curve was calculated and varied between 0.82 and 0.89. The positive and negative PVs for the CAP and UNICAP, which were assays with a high sensitivity and a high specificity, respectively, were estimated. In the clinically selected population (prevalence of CD, 1 in 3) the positive PV was about 55%, and in the general population (prevalence, 1 in 250) it was about 1%. The negative PVs for both CAP and UNICAP were close to 100%; thus, when the AGA test was negative, the risk for CD was small. Interestingly, five children had serum IgA levels below the detection limit (<0.07 g/liter) when on a gluten-free diet, whereas they had normal levels at the time of the first biopsy. In conclusion, the automated immunoassays--based on ImmunoCAP technology--for analysis of IgA-AGA had a reliability comparable to that of the in-house methods.

Tissue transglutaminase auto-antibodies in cord blood from children to become celiacs.

BACKGROUND: Determination of tissue transglutaminase auto-antibodies (tTGAA) has been shown to be a sensitive and specific diagnostic tool for large-scale screening for celiac disease. The purpose of this study was to measure tissue tTGAA in cord blood in infants that later developed celiac disease to evaluate if this assay could serve as a predictive tool for later development of celiac disease. METHODS: IgG tTGAA were analyzed in cord blood through immunoprecipitation from 51 future celiac patients and 102 age-matched controls. Cut-off level was set at 0.040. RESULTS: No difference in tTGAA levels was found between cord blood from infants who later developed celiac disease and controls (P = 0.746). 2/51 future celiac patients (3.9%) had levels above cut-off-value in cord blood, while 3/102 controls were positive (2.9%) (P = 1.000). tTGAA levels were higher in the 1980s and at the beginning of the 1990s than they have been in recent years (P = 0.003). CONCLUSIONS: Determination of tissue tTGAA in cord blood does not predict future celiac disease in children. tTGAA levels vary with time, which should be considered in retrospective studies analyzing tTGAA.