Overt Celiac Disease Research Articles

Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children

BackgroundThe relationship between the risk of celiac disease and both the age at which gluten is introduced to a child’s diet and a child’s early dietary pattern is unclear.MethodsWe randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years. Patients with positive serologic findings underwent intestinal biopsies. The primary outcome was the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age.ResultsOf the 707 participants who remained in the trial at 36 months, 553 had a standard-risk or high-risk HLA genotype and completed the study. At 2 years of age, significantly higher proportions of children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P=0.002) and overt celiac disease (12% vs. 5%, P=0.01). At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P=0.59) or overt disease (16% and 16%, P=0.78 by the log-rank test). At 10 years, the risk of celiac disease autoimmunity was far higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P=0.001), as was the risk of overt celiac disease (26% vs. 16%, P=0.05). Other variables, including breast-feeding, were not associated with the development of celiac disease.ConclusionsNeither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease. (Funded by the Fondazione Celiachia of the Italian Society for Celiac Disease; CELIPREV ClinicalTrials.gov number, NCT00639444.)

Monitoring the gluten free diet in children with celiac disease: Evaluation of fecal gliadin 33-mer equivalent in feces

s / Digestive and Liver Disease 46 (2014) e71–e84 e75 MONITORING THE GLUTEN FREE DIET IN CHILDREN WITH CELIAC DISEASE: EVALUATION OF FECAL GLIADIN 33-MER EQUIVALENT IN FECES Tiziana Galeazzi1, Simona Gatti 1,∗, Alice Guazzarotti 1, Sara Quattrini2, Veronica Albano1, Carlo Catassi1 1 Dipartimento di Clinica Pediatrica, Universita Politecnica delle Marche, Ancona, Italy 2 Scienze dell’Alimentazione, Universita degli Studi di Firenze, Firenze, Italy Objective: Methods of evaluating gluten free diet (GFD) compliance include clinical, serological and histological tests, but currently a sensitive, specific and non-invasive method is lacking. Detection of gliadin immunopeptides in faeces has recently been described as a good method for short-term assessment of gluten intake. We aimed to investigate clinical usefulness of this test in a group of CD children. Methods: CD children on at least 6-months-GFD and healthy children on normal diet were enrolled. 3-day food diary was used to monitor the diet before the enrollment and adherence to “anticontamination rules” was evaluated by a 16 points questionnaire. Gastrointestinal symptomswere evaluated through theGSRS scale. iVYLISA GIP test (Biomedal, Sevilla) was used to analyze stool samples, collected after 3 days of food-record. Correlation between symptoms, food diary and questionnaire analysis were found. Results: 63 CD children (mean age: 10.63 years, SD: 4.78 years) and 17 controls (mean age: 7.97 years, SD: 4.66 years) were enrolled.MeanGFDdurationwas 3.66 years, SD: 2.73 years. Overall 36.51% of CD children have detectable amount of gluten in stools compared to 100% of controls. Mean GIP values in CD group were significantly lower compared to controls (p<0.0001). Conclusions: First results identify a high percentage of CD children with detectable traces of gluten in faeces. This may indicate incomplete GFD compliance; however, food diary and questionnaire results need tobe correlated. iVYLISAGIP test doesnot require sophisticate instruments and is a non-invasive test, resulting a promisingmethod to assessGFDcompliance, especially in children. http://dx.doi.org/10.1016/j.dld.2014.07.029 INFANT FEEDING PATTERN, HLA STATUS, AND PREVALENCE OF CELIAC DISEASE Elena Lionetti 1,∗, Stefania Castellaneta2, Ruggiero Francavilla3, Alfredo Pulvirenti4, Elio Tonutti 5, Sergio Amarri6, Maria Barbato7, Cristiana Barbera8, Graziano Barera9, Antonella Bellantoni10, Emanuela Castellano11, Maria Giovanna Limongelli 12, Salvatore Pellegrino13, Carlo Polloni14, Claudio Ughi15, Giovanna Zuin16, Graziella Guariso17, Alessio Fasano18, Carlo Catassi19 1 Department of Pediatrics, University of Catania, Catania, Italy 2 Department of Pediatrics, San Paolo Hospital, Bari, Italy 3 Department of Developmental Biomedicine, University of Bari, Bari, Italy 4 Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy 5 Department of Immunology and Allergology, Udine Hospital, Udine, Italy 6 Department of Pediatrics, AO-IRCCS Santa Maria Nuova Hospital, Reggio Emilia, Italy 7 Department of Pediatrics, La Sapienza University, Roma, Italy 8 Department of Pediatrics, University of Torino, Torino, Italy 9 Department of Pediatrics, San Raffaele Hospital, Milano, Italy 10 Department of Pediatrics, Bianchi-Melacrino Morelli Hospital, Reggio Calabria, Italy 11 Department of Pediatrics, Gaslini Institute, Genova, Italy 12 Department of Pediatrics, Federico II University of Naples, Napoli, Italy 13 Cystic Fibrosis and Pediatric Gastroenterology Unit, University Hospital “G. Martino”, Messina, Italy 14 Department of Pediatrics, Rovereto Hospital, Rovereto, Italy 15 Department of Pediatrics, University of Pisa, Pisa, Italy 16 Department of Pediatrics, Buzzi Children Hospital, Milano, Italy 17 Department of Pediatrics, University of Padova, Padova, Italy 18 Division of Pediatric Gastroenterology and Nutrition and Center for Celiac Research, Harvard Medical School, Boston, USA 19 Department of Pediatrics, Universita Politecnica delle Marche, Ancona, Italy Objective: The relationship between age at gluten introduction, early dietary pattern and risk of celiac disease (CD) is unclear. The primary aim of the studywas to evaluate in a large cohort of infants at increased risk for CD the role of age at gluten introduction on the risk of CD-autoimmunity (CDA) and of overt CD. Methods: Newborns with a CD-affected first-degree relative were randomly assigned to be introduced to gluten at 6 months (group A) or at 12 months (group B). HLA genotype was determined at 15 months, and CD serology was evaluated at 15, 24, 36, and 60months, and at 8 and 10 years. Intestinal biopsies were performed in cases with positive serology. The primary outcome was the prevalence of CDA and overt CD by trial arm at five years of age. Results: The proportion of children developing CDA and overt CD was significantly higher in group A than in group B at 2 years

Infant feeding pattern, HLA status, and prevalence of celiac disease

Objective: The relationship between age at gluten introduction, early dietary pattern and risk of celiac disease (CD) is unclear. The primary aim of the study was to evaluate in a large cohort of infants at increased risk for CD the role of age at gluten introduction on the risk of CD-autoimmunity (CDA) and of overt CD.

Beyond the Intestinal Celiac Mucosa: Diagnostic Role of Anti-TG2 Deposits, a Systematic Review.

Aim: To review the existing literature on the role and significance of intestinal transglutaminase 2 immunoglobulin A deposits (TG2 deposits) in patients with overt celiac disease (CD), potential celiac disease (PCD), and other autoimmune or gluten-related conditions.Methods: We conducted a systematic review of studies published in English, evaluating presence and characteristics of TG2 deposits in subjects with overt CD, PCD, gluten-related diseases [dermatitis herpetiformis (DH), gluten-ataxia (GA)], autoimmune disorders (type-1 diabetes), and other conditions. Studies were identified through a MEDLINE search (1950–2013).Results: Twenty-three studies were included in the review. Eleven studies were performed in children. Overall TG2 deposits were present in 100% of adults with overt CD, while in children prevalence ranged from 73.2 to 100%. Six studies with an established definition of PCD were considered, prevalence of deposits ranging from 64.7 to 100%. A single study followed-up PCD patients with repeated biopsies and identified presence of intestinal deposits as the best marker to reveal progression toward villous atrophy. Two studies investigated presence of deposits in DH, reporting prevalence between 63 and 79%. A single study documented TG2 deposits in 100% of patients with GA. In children with type-1 diabetes (T1D), positivity of intestinal TG2 deposits ranged from 25 to 78%.Conclusion: Transglutaminase 2 IgA deposits seem to be a constant feature in overt CD patients and are frequently detectable in other gluten-related conditions (DH and GA). The vast majority of PCD patients express TG2 deposits at the intestinal level, but no sufficient data are available to exactly define their prognostic role as a marker of evolution toward overt CD. The frequent finding of TG2 deposits in the intestinal mucosa of patients with T1D is an interesting observation deserving further evaluation.

Serum level of celiac disease-associated antigliadin antibodies in psoriatic patients

Background Antigliadin antibodies (AGA) are markers of celiac disease (CD). Elevated levels of these antibodies are also seen in many other autoimmune, neurological, hematological, collagen vascular, and cutaneous disorders, even in the absence of clinically overt gastrointestinal disease. The possible relationship between psoriasis and CD has been attributed to the common pathogenic mechanisms of the two diseases. Aim of work The aim of the study was to assess the prevalence of serum level of immunoglobulin A [(IgA); AGA] in psoriatic patients and its correlation with disease severity. Patients and methods This study included 60 patients with psoriasis in whom severity was assessed with the Psoriasis Area and Severity Index (PASI) score, in addition to 30 healthy individuals who served as controls. Blood samples were taken from all patients and controls for detection of serum IgA (AGA) level by means of the enzyme-linked immunosorbent assay. Results A highly significant increase was found in the mean serum level of IgA (AGA) in psoriatic patients compared with controls. The serum level of IgA (AGA) was significantly correlated with the severity of psoriasis and with a history for food intolerance. Conclusion A high serum IgA (AGA) positivity rate was detected in severe psoriatic patients, and therefore these patients are at risk for latent and/or overt CD. Serological evaluation for serum level of IgA (AGA) should be considered in patients with severe psoriasis and a gluten-free diet must be prescribed.

New Aspects of the Diagnosis of Celiac Disease in Children, Adolescents, and Adults

of n spital, pital, .); and e, ology epartayo T he perception of celiac disease (CD) has changed in the past decade from a rare intestinal disease primarily recognized in childhood to a common, genetically determined disease with autoimmune components that affects people of all ages and involves several organs. Part of this change has been based on improved diagnostic measures and screening possibilities in the general population and particularly in at-risk populations, such as family members, patients with type 1 diabetes mellitus, and those with autoimmune thyroid disease. Several suggestions for new definitions of CD have recently been published; complete consensus has as yet not been obtained, but a framework is apparent (Table 1). All the published definitions agree on the presence of overt CD; silent CD, which is CD without recognized symptoms; and potential CD, which is the presence of CD antibodies and a normal duodenal biopsy result. The diagnostic criteria for CD have changed in practice because of these concepts and technological developments. The European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) recently developed and launched new ESPGHAN guidelines for the diagnosis of CD. These guidelines not only represent a sea change in thinking about how to reach the diagnosis of CD but also propose, for the first time, basing the diagnosis of an immune disorder largely, if not completely, on serologic tests. This comes at a time when the detection and largely the management of CD increasingly involve general practice. At the same time, the diagnostic algorithms are becoming complicated, necessitating specialized knowledge apart from procedures and biopsies. The diagnosis and indeed definition of CD have for decades been based on histologic damage to the small intestine. Previous diagnostic criteria promulgated by ESPGHAN and other organizations, such as the American Gastroenterology Association and a consensus group convened in Europe, pertinent to adults all

The Pediatric Symptom Checklist as screening tool for neurological and psychosocial problems in a paediatric cohort of patients with coeliac disease

To screen for neurological and behavioural disorders in a paediatric cohort of patients with coeliac disease (CD) in order to detect possible differences related to compliance with gluten-free diet (GFD). We recruited a cohort of 139 patients divided into three groups: A (40 patients with newly diagnosed CD), B (54 patients with CD in remission after GFD) and C (45 patients with potential CD). Patients first underwent a screening neurological visit, detecting signs associated with CD, and then were evaluated with Pediatric Symptom Checklist (PSC), a psychosocial screen for cognitive, emotional and behavioural problems. In the group B as compared to group A, there was a statistically significant decrease (p < 0.05) in the incidence of chronic fatigue, headache and inattention. The same applied to patients compliant to GFD vs. non-compliant. Potential coeliacs turning into overt CD had a higher incidence of headache and inattention compared with potential coeliacs showing normal mucosa. The PSC mean score in group A was statistically higher than in group B. Gluten-free diet had a positive impact on neuropsychiatric symptoms. We suggest the use of PSC in the routine follow-up of coeliacs in order to allow an early detection of psychosocial problems.

Plasmacytoid dendritic cells are scarcely represented in the human gut mucosa and are not recruited to the celiac lesion.

Celiac disease (CD) is a chronic small intestinal inflammation precipitated by gluten ingestion. According to case reports, interferon (IFN)-α administration may induce development of overt CD. Plasmacytoid dendritic cells (PDCs) were thought to be the source of IFN-α and promote a T helper type 1 response leading to lesion formation. Surprisingly and contradicting to earlier findings, PDCs were described as the main antigen-presenting cells (APCs) in human duodenal mucosa and particularly in CD. Here we show that when assessed by flow cytometry and in situ staining, PDCs represent < 1% of APCs in both normal duodenal mucosa and the celiac lesion. Low levels of IFN-α were detected in the celiac lesion assessed by western blot, reverse transcriptase (RT)-PCR, and immunohistochemistry. In four cell populations sorted from the celiac lesion (based on their expression of HLA-DR and CD45), we found that equally low levels of mRNA for IFN-α were distributed among these cell populations. Together, these results suggest that relatively small amount of IFN-α, produced by a variety of cell types, is present in the celiac mucosa. IFN-λ, a type III IFN important in intestinal antiviral defense, was produced mainly by APCs, but its expression was not increased in the celiac lesion.

Coeliac disease and C virus-related chronic hepatitis: a non association

BackgroundA higher prevalence of coeliac disease has recently been reported among patients with HCV-related chronic hepatitis. Moreover, development of clinically overt coeliac disease has been described in a number of HCV-related chronic hepatitis patients during α-interferon therapy. This prospective study was designed to evaluate 1) the prevalence of coeliac disease in patients with HCV-related chronic hepatitis; 2) the prevalence of HCV infection in patients with coeliac disease; 3) whether PEG interferon-α treatment might favour the development of coeliac disease in patients with chronic hepatitis C.Materials and methodsTwo hundred-ten consecutive patients (M/F = 140/70, range of age 35–58 years, median age 46.5 years) with biopsy proven chronic hepatitis C underwent serological screening for antiendomysial and tissue transglutaminase IgA antibodies. One hundred ninety-four coeliac patients (M/F = 52/142, range of age 18–74 years, median age 34 years) were screened for HCV antibodies. Positivity for HCV antibodies in coeliac disease patients was confirmed by detection of serum HCV-RNA by RT-PCR. This work was carried out in accordance to ethical guidelines of Declaration of Helsinki and was approved by Institutional Ethics Committee of the Second University of Naples. All patients gave informed written consent.Results1) none of the 210 HCV-related chronic hepatitis patients were positive for coeliac disease serologic screening; 2) prevalence of HCV infection among coeliac patients was 1.54% (3/194) which is comparable to that reported in the Southern Italy population; 3) PEG interferon-α treatment was not associated with development of coeliac disease either clinical or serological.Conclusions1) coeliac disease is not associated with HCV infection; 2) PEG interferon-α does not trigger celiac disease.

Prevalence and Natural History of Potential Celiac Disease in At-Family-Risk Infants Prospectively Investigated from Birth

To evaluate the frequency and the natural history of potential (serology positive/Marsh 0-1 histology) celiac disease (CD) in children with a family risk of CD and factors associated with potential instead of overt (serology positive/Marsh 2-3 histology) CD expression. Two-year follow-up study of 96 children (57 females; mean age: 29 ± 12 months) prospectively investigated from birth with: (1) a CD-affected first-degree relative; (2) positivity of serum IgA anti-tissue transglutaminase (tTG) or IgG antigliadin and IgA deficiency; and (3) the results of small intestinal biopsy. Children with potential CD were advised to remain on a gluten containing diet, repeat the celiac antibodies every 6 months, and to have an intestinal biopsy performed in case of persistently high anti-tTG level. Factors discriminating between potential and overt CD were analyzed by decision tree analysis based on the C4.5 algorithm. Twenty-four children had potential and 72 overt CD. The stronger predictors of potential CD were lack of symptoms, anti-tTG level lower than 11-fold the upper normal limit, age lower than 24 months, and breastfeeding longer than 8 months. Eighteen out of 21 (86%) patients with potential CD continuing a gluten-containing diet became antibody negative, 1/21 (5%) developed overt CD, and 2/21 (9%) had fluctuating antibodies levels after 2 years. The prevalence of potential CD and the percentage of short-term loss of CD-related-antibodies are high in infants at-family-risk for CD. In symptomless children with a positive celiac serology, the decision of performing an intestinal biopsy should be preceded by a period of repeated serological testing.

PTU-159 Self reporting of gluten sensitive GI symptoms in primary care: should we accept the diagnosis of coeliac disease without further investigations?

IntroductionMany unselected patients presenting to gastrointestinal (GI) clinics self-report that they have symptoms related to the ingestion of gluten. For this reason we undertook a prospective and systematic evaluation of...

Persistently positive gliadin antibodies without transglutaminase antibodies in the elderly: Gluten intolerance beyond coeliac disease

Background The specificity of the conventional gliadin antibody test is considered low. Aims We explored whether gliadin antibody(AGA)-positivity without tissue transglutaminase antibodies (tTGA) is persistent in the elderly population and whether such positivity indicates overt or potential coeliac disease in genetically predisposed individuals. Methods AGA and tissue transglutaminase antibody were measured in 2089 elderly individuals twice with a three-year interval. AGA-positive but tissue transglutaminase antibody-negative subjects with coeliac-type human leucocyte antigen (HLA) were examined and underwent gastroduodenal endoscopy (cases). Small-bowel mucosal villous morphology and densities of CD3+ and γδ+ intraepithelial lymphocytes and the occurrence of tissue transglutaminase-specific IgA deposits were analysed. Randomly selected persistently AGA-negative age- and sex-matched subjects served as controls. Results AGA-positivity was persistent in 81% of those initially positive. Amongst the 49 clinically studied and 36 endoscopied cases only one (2.8%) had coeliac disease. Many (54%) showed signs of inflammation in the biopsy, without villous atrophy. Coeliac-type HLA was not over-represented in the persistently AGA-positive compared to the general population. Persistently AGA-positive coeliac-type HLA-positive subjects had more gastrointestinal symptoms than AGA-negative controls. Conclusions AGA-positivity is often persistent. Overt coeliac disease is seldom found behind persistent AGA-positivity, but this characteristic is associated with mucosal inflammation and gastrointestinal symptoms at least in HLA-positive individuals.

Are Patients with Potential Celiac Disease Really Potential? The Answer of Metabonomics

Celiac disease (CD) is an autoimmune disorder caused by a permanent sensitivity to gluten in genetically susceptible individuals. Accurate diagnosis of CD at an early stage and its treatment with a gluten-free diet (GFD) are important for optimum treatment and prognosis. Recently, by employing a noninvasive metabonomic approach, we have shown that CD has a well-defined metabonomic signature. Here we address potential CD patients, defined as subjects who do not have, and have never had, a jejunal biopsy consistent with clear CD, and yet have immunological abnormalities similar to those found in celiac patients. Sixty-one overt CD patients at diagnosis, 29 patients with potential CD, and 51 control subjects were examined by (1)H NMR of their serum and urine: out of 29 potential CD patients, 24 were classified as CD and 5 as control subjects. Potential CD largely shares the metabonomic signature of overt CD. Most metabolites found to be significantly different between control and CD subjects were also altered in potential CD. Our results demonstrate that metabolic alterations may precede the development of small intestinal villous atrophy and provide a further rationale for early institution of GFD in patients with potential CD, as recently suggested by prospective clinical studies.

Gluten‐dependent Small Bowel Mucosal Transglutaminase 2–specific IgA Deposits in Overt and Mild Enteropathy Coeliac Disease

In coeliac disease, immunoglobulin (Ig)A-class autoantibodies against transglutaminase-2 are produced in the small intestinal mucosa, where they are deposited extracellularly. It remains unclear whether positive intestinal transglutaminase-2-targeted IgA deposits in subjects having normal small bowel mucosal morphology are signs of early-stage coeliac disease. We evaluated the gluten dependency of these deposits in overt and mild enteropathy coeliac disease. All together 48 subjects suspected of coeliac disease but having normal small bowel mucosal villi were enrolled; 28 of them had latent coeliac disease. The remaining 20 having positive intestinal IgA deposits adopted a gluten-free diet before villous atrophy had developed. For comparison, 13 patients with overt coeliac disease and 42 noncoeliac controls were studied. Small bowel mucosal transglutaminase-2-specific autoantibodies were compared with villous morphology, intraepithelial lymphocyte densities, and serum coeliac autoantibodies. Intestinal IgA deposits were seen in all but 1 of the patients with latent coeliac disease, when the morphology was still intact; the intensity of these deposits increased as villous atrophy developed and decreased again on a gluten-free diet. In 20 patients with intestinal IgA deposits in normal villi, the intensity of the deposits decreased with the diet similarly to that seen in patients with overt coeliac disease. Mucosal IgA deposits were seen initially only in 5% of noncoeliac controls and in 8% after extended gluten consumption. The response of small bowel mucosal transglutaminase-2-specific IgA deposits for dietary intervention was similar in overt and mild enteropathy coeliac disease. Detection of such IgA deposits thus offers a good diagnostic tool to uncover early-stage coeliac disease.

Flow cytometric analysis reveal an expansion of CD4+CD25+FOXP3+ regulatory T cells in overt celiac disease and in vitro challenged mucosa

Flow cytometric analysis reveal an expansion of CD4+CD25+FOXP3+ regulatory T cells in overt celiac disease and in vitro challenged mucosa

Urinary Stone Disease in Adults With Celiac Disease: Prevalence, Incidence and Urinary Determinants

Intestinal diseases may cause urinary stone disease via hyperoxaluria or diarrhea induced hyperconcentrated acidic urine. Data are missing on urinary stone disease in celiac disease, a common malabsorptive disorder. In this study we analyzed urinary stone disease and urine composition in adults with celiac disease. Study patients were 18 years or older, untreated, and newly diagnosed with celiac disease by serum markers and jejunal biopsy. Clinical presentation of celiac disease was assessed focusing on 5 disorders of diarrhea, and deficiency of calorie (low body mass index or weight loss), lipid (low prothrombin time or low serum lipids), iron (low hemoglobin or low serum ferritin) and calcium (low serum calcium or low bone densitometry). Urinary stone disease history was assessed by questionnaire (imaging, stone excretion, stone disruption/removal). Urinary variables were measured in a 24-hour collection in a subgroup of patients. Under untreated conditions (baseline) urinary stone disease was independent of celiac disease presentation and more prevalent in patients with celiac disease than in a population sample used as a control (608 and 3,540, 7.9% and 5.0%, sex and age adjusted odds ratio 4.0, 95% CI 2.7-5.9). Excluding from analysis individuals with baseline urinary stone disease, the incidence of urinary stone disease history was not significantly different between the treated celiac disease (gluten-free diet) and control population (458 and 3,003, 2.4% vs 3.9%). The urine of untreated patients with celiac disease differed from that of healthy volunteers with 120% higher oxalate and 43% lower calcium (in 45 and 45, p <0.001). A gluten-free diet corrected urinary abnormalities (p <0.01). Urinary stone disease risk is high in untreated patients with celiac disease independent of overt malabsorption. Hyperoxaluria is likely the underlying disorder. A gluten-free diet reduces urinary stone disease risk and oxaluria.

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

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). 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). 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). 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.

Hyperamylasemia, Reactive Plasmacytosis, and Immune Abnormalities in a Patient with Celiac Disease

Celiac disease (CD) is an autoimmune disease that occurs in genetically predisposed individuals, characterized by a permanent intolerance to ingested wheat gluten or related proteins from rye and barley, and immunologically mediated inflammatory damage of the small intestinal mucosa [1]. Environmental factors such as gluten administration in childhood and breastfeeding play a synergetic role in the induction of disease. Serologic surveys have shown that CD is a common disease, possibly affecting ∼ 1% of the population [2], whereas overt CD is rare, suggesting a high proportion of subclinical disease. Here we report a case of CD who demonstrated persistently elevated levels of serum amylase and lipase, reactive plasmacytosis in the bone marrow, and hypergammaglobulinemia characterized by increased levels of serum immunoglobulin (Ig) A and IgG. Immunoprecipitation assay showed that amylase was bound to polyclonal

Occurrence of overt celiac disease in the elderly following total thyroidectomy

We report the case of a female patient in whom gluten-induced entheropathy was revealed at the age of 71 yr by resistance to treatment with levothyroxine (L-T4), calcium carbonate and alfacalcidol. Hypothyroidism and hypoparathyroidism were the consequence of a total thyroidectomy performed at the age of 65 yr for a large multinodular goiter. Six months after thyroid ablation the patient started to complain of abdominal pain, diarrhea and weight loss. Following, anemia and osteopenia were documented. A progressive increase of replacement therapy for hypothyroidism and hypoparathyroidism was necessary. The clinical presentation suggested a malabsorption syndrome: celiac disease (CD) was diagnosed by serological markers and duodenal biopsy. Following gluten-free diet a normalization of clinical and serological findings was observed, bone mass density improved and a reduction of L-T4, calcium and vitamin D requirements was observed.

EARLY EPITHELIAL ALTERATIONS IN "LATENT/AT RISK" CELIAC PATIENTS WITH NORMAL HISTOLOGY

Background: Celiac disease (CD) is an intestinal inflammatory disease induced in genetically susceptible people by gluten ingestion. A known mechanism is the adaptive response to immunodominant peptides of α-gliadin recognized by gliadin specific CD4+ T cells in the LP driving the anti-tissue transglutaminase (TTG) antibody response. Mucosal damage is mediated by CD8+ intraepithelial lymphocytes recognizing innate epithelial stress ligands. The α-gliadin p31-49 peptide, unrecognized by CD4+ T cells, triggers epithelial stress. Hypothesis: A subset of "latent/at risk" CD patients with normal histology display markers of stress precluding T cell activation. Methods: 42 underwent duodenal biopsies for GI symptoms, family history(FH) of CD or positive anti-TTG abs. 37 pts with normal histology were divided into controls or "latent/at risk" CD based on HLA-DQ2 or DQ8, presence of anti-TTG abs, or 1st or 2nd-degree FH. Controls did not have a FH or anti-TTG abs. Biopsies were stained for IL-15 and Hsp70 and interpreted by GI path in a blinded manner scoring Hsp70 from 0-3 and IL-15 from 0-4. Results: Increased IL-15 (P < 0.007) and Hsp70 (P < 0.00008) expression was seen in the latent group versus controls. HLA type made no significant difference in expression of either marker. Surprisingly, when analyzed based on TTG ab, epithelial IL-15 (P < 0.006) and Hsp70 (P < 0.001) scores were higher among the TTG neg versus TTG pos and controls, suggesting IL-15 and Hsp70 expression are not linked to the CD4+ response. Conclusions: These results indicate latent CD patients with apparent normal histology and CD4+ response display markers of epithelial cell stress. Aberrant innate responses may play a role without CD4+ activation. Future studies will determine whether high levels of IL-15 and Hsp70 is predictive of overt CD.