Celiac Disease Antibodies Research Articles

Atypical presentations of celiac disease

Abstract In this study we evaluated the association of celiac disease in 81 children with autoimmune disease and genetic syndromes over a two years periods (January 2014 to July 2016) in Pediatric Clinic in Constanta. Because the extraintestinal symptoms are an atypical presentation of celiac disease we determined in these children the presence of celiac disease antibodies: Anti-tissue Transglutaminase Antibody IgA and IgA total serum level as a screening method followeds in selective cases by Anti-tissue Transglutaminase Antibody IgG, anti-endomysial antibodies, deamidated gliadin antibodies IgA and IgG and intestinal biopsia. In our study 8 patients had been diagnosed with celiac disease with extraintestinal symptoms, of which 4 with type 1 diabetes, 1 patient with ataxia, 2 patients with dermatitis herpetiformis and 1 patient with Down syndrome that associate also autoimmune thyroiditis, alopecia areata, enamel hypoplasia.

Screening for Coeliac Disease: Are We Good at It?

Department of Paediatrics, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland Coeliac disease (CD) is an immune reaction to gluten in genetically predisposed subjects. CD is likely to affect approximately 1% of the population of England [1]. The age of presentation is influenced by the age of introduction of gluten into the diet. CD may present as a large variety of non-specific signs and symptoms. Children with CD may experience unexplained poor growth following the introduction of gluten, delay puberty, abnormal stools and constipation. General irritability, chronic abdominal pain, abnormal liver biochemistry, abdominal distension and buttock wasting have been reported. CD should be considered in children presented with iron deficiency anaemia, growth failure with or without gastrointestinal symptoms. Patients with CD may experience low bone mineral density [2], but similar health-related quality of life as their peers without CD [3]. However individuals with CD may exhibit no symptoms. Certain individuals are at an increased risk; such as patients with type 1 diabetes mellitus, Down’s syndrome and Turner’s syndrome, for example, and presymptomatic screening is advised [4]. Diagnosis can be confirmed by flat mucosa on jejunal biopsy followed by the resolution of symptoms and catch up growth upon gluten withdrawal. Diagnostic serological tests have been developed. These’s include IgA anti-tissue transglutaminase (IgA-tTG) and antiendomysium antibody (EMA) values. It is important to measure serum IgA level and IgG-tTG values should be considered in those with low IgA levels. In previous study, biopsyproven CD and positive EMA were reported in 60% of those with elevated IgA-tTG levels above the reference range, whereas biopsy-proven CD was reported in all patients with positive EMA [5]. European Society for Paediatric Gastroenterology, Hepatology and Nutrition working group suggested that typing for HLA-DQ2 and HLA-DQ8 can be helpful where there is uncertain diagnosis of CD; such as cases with negative CD antibodies and mild changes on biopsy or with strong clinical suspicion, highly specific CD antibodies and biopsies are not going to be performed, for example [4]. Monitoring for CD is required in children with unexplained poor growth, delayed puberty or unexplained gastrointestinal symptoms and screening in asymptomatic individuals who are at an increased risk is advised.

Towards Finding More Diagnostic Serological Markers in Celiac Disease: Can Deamidated Gliadin Peptide Antibodies Help to Our Babies?

Dokuz Eylul University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Izmir, TURKEY Celiac disease (CD) is a common immune-mediated enteropathy triggered by gluten in genetically susceptible individuals with an overall prevalence almost 1% in different countries [1]. The diagnosis of the disease is classically based on a combination of serologic tests and characteristic intestinal biopsy findings [2]. In a recent meta-analysis performed by European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Working Group of Celiac Disease Diagnosis, 16 studies have been reviewed and anti-antiendomysial (EmA) and anti-tissue transglutaminase (tTG) IgA antibodies have been found more accurate tests for the diagnosis of CD [2]. In this meta-analysis, their sensitivities have been detected more than 90%, and specifities have been found 98.2% for anti-EmA and >90% for anti-tTG [2]. With the improvement of serological tests, diagnosis of CD without intestinal biopsies has been suggested in some defined situations [3]. On the other hand, despite the high diagnostic performance of anti-tTG and anti-EmA antibodies for CD, they have lower accuracy in children younger than 2 years of age and patients with selective IgA-deficiency [4]. ESPGHAN Working Group of CD Diagnosis prepared new guidelines for CD diagnosis in 2012 [5]. According to these criteria, diagnosis is based on the combined evaluation of symptoms, serological tests, biopsy findings, and human leukocyte antigen (HLA) typing [5]. In symptomatic patients who have anti-tTG titers >10 times the upper limit of normal and positivity for EmA, it is possible to diagnose CD without performing the intestinal biopsy [5]. It has been proposed that, for patients with IgA deficiency the decision should be made from the results of the IgG class antibody tests [5]. Typing of HLA-DQ2 and HLA-DQ8 is a useful tool, which has a diagnostic sensitivity of > 96 %. Therefore, a negative result of HLA-DQ2 and/or DQ8 testing makes a diagnosis of CD highly unlikely [5,6]. Recent studies showed that anti-deamidated gliadin peptide (DGP) antibodies had higher sensitivity and specificity than conventional anti-gliadin antibodies [7], consequently anti-DGP antibodies joined anti-tTG and anti-EmA as tests with high diagnostic performance [8,9,10]. On the other hand, some studies demonstrated superior diagnostic value of anti-tTG to anti-DGP antibodies even in patients younger than 2 years-old [11]. In this first issue of the Journal, Oana et al [12] investigated the accuracy of these antibodies in symptomatic infants. They evaluated the diagnostic value of combined IgA/IgG DGP/tTG screen assay in anti-IgA tTG or anti-EmA negative children younger than 2 yearsold. All children had normal total IgA concentration and were consuming gluten at the time of the study. Diagnosis of celiac disease was made according to intestinal biopsy findings. They found the sensitivity of combined IgA/IgG DGP/tTG screen assay (95.4 %) higher than both antitTGA (86.3%) and anti-EmA (91%) antibodies in this age group of children [12]. They concluded that better performance of this combined tests might preclude repeated intestinal biopsies in young symptomatic children who have negative tTG/EmA serology. Recent ESPGHAN guideline also proposes that anti-DGP antibodies may be used as additional tests in patients who are negative for other celiac spesific antibodies but have symptoms compatible with celiac disease, especially in patients younger than 2 years-old [5]. In conclusion, intestinal biopsy is an invasive diagnostic method especially in young children. Further more sensitive serological tests can provide the definite diagnosis of celiac disease especially in younger age group without this invasive procedure.

Prevalence of celiac disease and related antibodies in patients diagnosed with irritable bowel syndrome according to the Rome III criteria. A case-control study.

The cost-effectiveness for screening for celiac disease (CD) in patients with irritable bowel syndrome (IBS), specifically in the diarrhea (IBS-D) subtype, is beneficial if the prevalence is >1%. However, recent studies have shown controversial results. In this large case-control study, our aim was to determine the prevalence of CD and a panel of related antibodies in patients diagnosed with IBS. Four hundred IBS patients (Rome III) and 400 asymptomatic healthy controls were prospectively evaluated using antihuman tissue transglutaminase (h-tTG IgA) and deamidated gliadin peptide antibodies (DGP II IgA and DGP II IgG). Duodenal biopsy was performed on the patients that were positive for the h-tTG IgA and/or DGP II IgG antibodies. The mean age of the population was 44.47±18.01years and 335 (82%) of the subjects were women. Twenty-one patients and six controls had at least one positive test for CD (5.25% VS 1.5%, p=0.003, OR 3.63 [95% CI 1.4-9.11]). Eighteen patients were positive for h-tTG and/or DGP-II IgG. Histologic confirmation of CD was 2.5% in the IBS patients vs 0.5% in the controls (p=0.04, OR 5.21). The IBS-D subtype had the highest prevalence for serological positivity (12.7%). Up to 5.2% of the patients with IBS according to the Rome III criteria were positive for at least one of the CD-related antibodies and 2.5% had biopsy-confirmed CD. Therefore, in our population, screening for CD in subjects with IBS appears to be a reasonable strategy, especially in the IBS-D subgroup.

Decrease by 50% of plasma IgA tissue transglutaminase antibody concentrations within 2 months after start of gluten-free diet in children with celiac disease used as a confirming diagnostic test

Background Histological examination of small bowel biopsies is normally the gold standard for the diagnosis of celiac disease (CD). The objective of this study was to investigate whether the rate of decreases in elevated plasma IgA tissue transglutaminase antibody (IgA-tTG) and/or IgG deamidated gliadin peptides antibody (IgG − DGP) concentrations could be used as a confirming test for CD in children on a gluten-free diet (GFD) when biopsy was omitted in the diagnostic process. Methods In this retrospective study we compared children (≤18 years old) with a CD-confirming biopsy (n = 16) to children without a biopsy (n = 18). After initiation of GFD the antibody half-life (the time (T½) when the antibody concentration is 50% decreased) was determined in all children. Results Children with a biopsy (IgA-tTG, T½ = 1.9 months; IgG − DGP, T½ = 2.2 months) and children without a biopsy (IgA-tTG, T½ = 1.6 months; IgG − DGP, T½ = 2.7 months) had comparable T½ (mean) results (p < 0.05) supporting that all children had the CD diagnosis. Conclusions When biopsy was omitted a rapid rate of decrease in CD antibody concentrations confirmed the CD diagnosis in children on GFD. The half-lives (T½) of IgA-tTG were less than 2 months in CD children.

Severe Osteoporosis in a Young Woman With Celiac Diseases due to Vitamin D Deficiency

Osteoporosis and other related clinical features from secondary hyperparathyroidism due to the intestinal malabsorption of vitamin D and calcium can often be misdiagnosed. Symptoms such as weight loss, gastrointestinal discomfort, hypocalcemia, anemia and neurological symptoms like paresthesia and leg pain have to be considered as celiac disease (CD)-related consequences. We report the case of a 37-yearold woman with biannual history of weight loss, extreme fatigue, chest pain, paresthesia, and leg pain. After full biochemical and endocrine assessment, we found anemia with severe iron deficiency, hypocalcemia, vitamin D deficiency and high parathyroid hormone level. Moreover, on whole body dual-energy X-ray absorptiometry, osteoporosis with diffuse metabolic changes was present, antibodies for CD were positive and renal function was normal. After these examinations, the patient was diagnosed with secondary hyperparathyroidism due to CD. Treatment with gluten-free diet, high doses of vitamin D and calcium revealed osteoporosis and hyperparathyroidism was treated for several months. Secondary hyperparathyroidism due to CD has to be considered during the evaluation of patients with weight loss, hypocalcemia, anemia and other non-specific metabolic, neurological and gastrointestinal symptoms. Early gluten-free diet treatment, high doses of vitamin D supplements and calcium must be used to treat osteoporosis and secondary hyperparathyroidism in the meantime. Treatment with bisphosphonates is not necessary for osteoporosis due to CD.

Encefalitis refractaria debido a enfermedad celíaca seronegativa: caso clínico

The celiac disease is an autoimmune bowel disease trigger by gliadine proteins, that can has systemic involvement with varied neurological manifestation since polineuropathy, ataxia, epilepsy, migraine to encephalitis. The aim of the current work is to report a case of possible refractory encephalitis due to celiac disease. A 45 years-old man with histopathologic diagnosis of celiac disease but negative celiac antibodies developed encephalic, brainstem and periphery nervous system manifestations: cognitive declaim and seizures, diplopia and ataxia, polyneuropathy and polyradiculopathy respectively; inflammatory cebrospinal fluid and cortico-subcortical and multiple brainstem lesions with mild contrast enhancement; the neurologic deficits progress in spite of gluten a free diet and immuno-suppressive treatment. During the illness process some pathologies with nervous system and intestinal involvement were discarded: sarcoidosis, systemic lupus; Sjogren syndrome, paraneoplastic syndromes, Whipple disease, AIDS and B12 vitamin deficit. The encephalitis is an infrequent clinical manifestation of the celiac disease despite the high prevalence of the celiac disease in the general population. It presents with numerous differential diagnosis, with requires high suspicious diagnosis.

Enamel organ proteins as targets for antibodies in celiac disease: implications for oral health

Enamel defects in permanent and deciduous teeth may be oral manifestations of celiac disease. Sometimes they are the only sign that points to this underdiagnosed autoimmune pathology. However, the etiology of these specific enamel defects remains unknown. Based on previously reported cross-reactivity of antibodies to gliadin with the enamel proteins, amelogenin and ameloblastin, we analyzed (using immunohistochemistry) the ability of anti-gliadin IgG, produced during untreated disease, to recognize enamel organ structures. We used swine germ teeth as a tissue model because they are highly homologous to human teeth in terms of proteins and development biology. Strong staining of the enamel matrix and of the layer of ameloblasts was observed with serum samples from women with celiac disease; high IgG reactivity was found against both gliadin peptides and enamel matrix protein extract, but there was no IgG reactivity against tissue antigens. In line with these findings, the gamma globulin fraction from gliadin-immunized BALB/c mice showed a similar staining pattern to that of amelogenin-specific staining. These results strongly suggest a pathological role for antibodies to gliadin in enamel defect dentition for both deciduous and permanent teeth, considering that IgG can be transported through the placenta during fetal tooth development.

Does celiac sero-diagnosis always require a tertiary referral centre confirmation? Our experience in Marche region

Background: Evaluation of celiac autoantibodies is a crucial step in the diagnostic algorithm of celiac disease (CD). The need of intestinal biopsy mainly relies on TTG IgA levels (with biopsy still needed if levels are less than 10 times the ULN, subdiagnostic levels [SDLs]). Aim: To evaluate the agreement of serological CD markers between different regional peripheral laboratories (PLs) and our referral regional laboratory (RL) in Salesi Children’s Hospital (Ancona). Methods: Childrenwith a final diagnosis of CD confirmed in our centre (May 2014–April 2015) and a previous (within 1 month) serological evaluation (TTG IgA and DGP IgG) performed in one PLs were included. Levels (times the ULN) of TTG IgA and DGP IgGwere compared between the RL and the PLs. Results: Forty-one subjects (mean age: 6.2 years) with a diagnosis of CD were included. Overall the RL confirmed abnormal CD antibodies detected in PLs in 100% of patients. A small proportion were discordant in TTG IgA levels: 10% with SDLs detected in a PL had diagnostic levels in the RL, while 17% with>10 times the ULN in a PLwere found to have SDLs in the RL, requiring confirmation by biopsy. Bland Altaman analysis suggested that the levels of TTG IgA in the RL was on average 4.8 times higher (SD 14.8) than the levels in the PLs with wide limits of agreement (95% limit of agreement: −33.83 to 24.20 times). Conclusion: In our regional setting the determination of serological CDmarkers in a PLswas overall reliable andwe found a good correlationwithmeasurement in the RL. Howeverwe still consider the confirmation in our RL a fundamental step in the diagnostic process.

Structural Basis for Antigen Recognition by Transglutaminase 2-specific Autoantibodies in Celiac Disease

Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut IgA plasma cell of a celiac disease patient. The antibody recognizes one of four identified epitopes targeted by antibodies of plasma cells of the disease lesion. The binding interface was identified by small angle x-ray scattering, ab initio and rigid body modeling using the known crystal structure of TG2 and the crystal structure of the antibody Fab fragment, which was solved at 2.4 Å resolution. The result was confirmed by testing binding of the antibody to TG2 mutants by ELISA and surface plasmon resonance. TG2 residues Arg-116 and His-134 were identified to be critical for binding of 679-14-E06 as well as other epitope 1 antibodies. In contrast, antibodies directed toward the two other main epitopes (epitopes 2 and 3) were not affected by these mutations. Molecular dynamics simulations suggest interactions of 679-14-E06 with the N-terminal domain of TG2 via the CDR2 and CDR3 loops of the heavy chain and the CDR2 loop of the light chain. In addition there were contacts of the framework 3 region of the heavy chain with the catalytic domain of TG2. The results provide an explanation for the biased usage of certain heavy and light chain gene segments by epitope 1-specific antibodies in celiac disease.

IgG anti-tTG responses in different autoimmune conditions differ in their epitope targets and subclass usage.

Antibodies of the IgA class directed against the enzyme tissue transglutaminase (tTG) are highly specific for coeliac disease (CD). IgG antibodies to tTG also occur in CD, and have also been reported in autoimmune diseases such as type 1 diabetes mellitus and Crohn's disease. In comparison to the IgA anti-tTG response, little is known of the IgG anti-tTG response in terms of epitope specificity and IgG subclass usage. The aim of this study was to investigate and compare epitopes recognised by CD and non-CD IgG anti-tTG antibodies, and determine the relative proportions of the IgG subclasses comprising this response. IgG anti-tTG positive individuals who did not have CD were identified by screening groups of patients with type I diabetes mellitus, Crohn's disease and granulomatosis with polyangiitis. Results from ELISA blocking experiments and mutant tTG antigens demonstrate that non-CD IgG anti-tTG bind different epitopic determinants to CD IgG anti-tTG. The IgG subclass usage of coeliac disease and type 1 diabetes was dominated by IgG1, whereas this IgG subclass was infrequently a component of the IgG anti-tTG response in diseases such as granulomatosis with polyangiitis and Crohn's disease. The differences in epitope specificity and subclass usage of IgG anti-tTG observed between CD and non-CD individuals may be due to the differing mechanisms underlying tTG autoimmunity.

Prevalence of serum celiac antibodies in a multiracial Asian population--a first study in the young Asian adult population of Malaysia.

BackgroundCeliac disease (CD) is an immune-mediated disorder induced by the ingestion of gluten in genetically susceptible persons. The prevalence of CD in Malaysia is unknown. We aim to determine the seroprevalence of CD antibodies and also investigate the correlation between H. pylori infection and CD in the young and healthy multiracial Malaysian population.MethodsHealthy young adult volunteers between the ages of 18–30 years were consecutively recruited from June 2012 to May 2014 at the University of Malaya Medical Centre (UMMC), Kuala Lumpur. Serum samples from all the participants were tested for anti-gliadin antibody immunoglobulin A/immunoglobulin G (IgA/IgG) and anti-tissue transglutaminase antibody (tTG) IgA/IgG. Samples positive for both anti-gliadin and anti-tTG were further validated for anti-human endomysial IgA antibodies (EmA). Serological diagnosis of CD was made when anti-gliadin, anti-tTG and anti-EmA were positive.Results562 qualified participants with mean age 24 ± 2.4 years old were recruited into our study. CD was found in 7 participants where most of them were asymptomatic and unaware of their CD status. The median of anti-gliadin and anti-tTG IgA/IgG value was 38.2 U/ml (interquartile range, 28.3–60.4 U/ml) and 49.2 U/ml (interquartile range, 41.1–65.9 U/ml), respectively. Seroprevalence of CD antibodies was 1.9% (6 out of 324) in female while only 0.4% (1 out of 238) in male. Seroprevalence among Malay was 0.8% (2 of 236), Chinese was 1.7% (3 of 177) and Indian was 1.3% (2 of 149). Overall, seroprevalence of CD antibodies in healthy asymptomatic adults in the Malaysian population was 1.25% (95% CI, 0.78%-1.72%). No significant relationship was discovered between CD and H. pylori infection.ConclusionsThe seroprevalence of CD antibodies in healthy young adults in the Malaysian population was 1.25% (1 in 100). CD is underdiagnosed and it could be a much greater problem in Malaysia than previously thought.

Clinical and immunological relevance of anti-neuronal antibodies in celiac disease with neurological manifestations.

To assess anti-neuronal antibodies (NA) prevalence and their correlation with neurological disorders and bowel habits in celiac disease (CD) patients. Neurological manifestations are estimated to occur in about 10% of celiac disease patients and NA to central nervous system (CNS) and enteric nervous system (ENS) are found in a significant proportion of them. Little is known about the clinical and immunological features in CD patients with neurological manifestations. NA to CNS and ENS were investigated in 106 CD patients and in 60 controls with autoimmune disorders by indirect immunofluorescence on rat / primate cerebellar cortex and intestinal (small and large bowel) sections. IgG NA to CNS (titer 1:50 - 1:400) were positive in 23 celiacs (21%), being more frequently detected in those with neurological disorders that in those without neurological dysfunction (49% vs. 8%, P< 0.0001). Of the 26 celiacs (24%) with IgG NA to ENS, 11 out of 12 with an antibody titer > 1:200 had severe constipation. Only one patient with cerebellar ataxia and intestinal sub-occlusion was positive for NA to CNS and ENS. NA to CNS and ENS were found in 7% and 5% of controls, respectively. In CD the positivity of NA to CNS can be regarded as a marker of neurological manifestations. High titer NA to ENS are associated with severe constipation. The demonstration of NA to CNS and ENS suggests an immune-mediated pathogenesis leading to central neural impairment as well as gut dysfunction (hence constipation), respectively.

Serum anti endomysial and anti transglutaminase antibodies in patients with connective tissue diseases

The detection of anti-transglutaminase IgA (tTG) and anti-endomysial (EMA) is used for screening of celiac disease (CD) with a sensitivity and specificity of 90 and 99% respectively. There is an association between CD and connective tissue diseases (CTD). To report the frequency of IgA tTG and EMA in patients with a definite diagnosis of CTD and inflammatory arthropathies (IA). One hundred forty nine patients, aged 19 to 86 years (133 females) with CTD and IA were studied. tTG were determined by ELISA and EMA by indirect immunofluorescence. Eight participants had at least one positive antibody (5.4%, confidence intervals (CI) = 1.8-9), six had both (4.0% CI = 0.9-7.2) and two had only tTG positive. An intestinal biopsy was performed in four of these participants, finding a marked villous atrophy in three and partial atrophy in one. Five percent of this group of patients with CTD or IA had positive antibodies for CD.

Celiac disease in children: is it a problem in Kuwait?

BackgroundCeliac disease (CD) is a chronic inflammatory disease of the small intestine triggered by gluten ingestion. The objective of this study is to describe our experience with CD children in Kuwait.MethodsThe records of children with CD seen in the pediatric gastroenterology unit between February 1998 and December 2010 were retrospectively reviewed. Patients were referred because of symptoms or positive CD antibody screening of a high-risk group (type 1 diabetes and Down syndrome).ResultsForty-seven patients were diagnosed: 53% were symptomatic and 47% were identified by screening. The median age at diagnosis was 66 (range 7–189) months. All cases were biopsy-proven except one. The symptomatic patients were significantly younger than those identified following screening (P<0.004). In the whole group, 66% were females and 77% were Kuwaitis; 9% had a positive family history of CD. The estimated cumulative incidence was 6.9/105. The median duration of symptoms before diagnosis was 8.5 (range 2–54) months. Failure to thrive was the most common presenting complaint (72%) followed by diarrhea (64%) and abdominal distension (56%). Atypical manifestations were seen in 60% of patients. Underweight and short stature were confirmed in 19% and 17% of patients, respectively. Overweight and obesity were detected in 14% and 6%, respectively. CD serology was based on a combination of antiendomysial and antigliadin antibodies. The median follow up was 24 (range 12–144) months. All patients were commenced on a gluten free diet, but good compliance was only achieved in 78%.ConclusionThe low frequency of childhood CD in Kuwait could probably be attributed to either an underestimation of the atypical presentations or failure of proper screening. Also, adherence to a gluten free diet is a major problem in our population.

Celiac Disease Screening Rates Vary by Race in Pediatric Patients With Type 1 Diabetes Mellitus at a Tertiary Care Center

Introduction: Screening for celiac disease (CD) is advocated in high-risk groups such as patients with type 1 diabetes mellitus (T1D) who carry similar genetic risk factors. However, little is known about screening and serological positivity in African Americans (AAs) with T1D. The aim of this study was to compare the rates of CD screening and antibody positivity in pediatric African American (AA) and Caucasian (Ca) patients with T1D at a single tertiary care center. Methods: A retrospective chart review was performed for patients seen between February 1999 and June 2013. Medical records were abstracted according to ICD-9 codes for T1D. Patients aged 18 years and younger were included, and self-identified race was recorded. Results for tissue transglutaminase (TTG) IgA, endomysial (EMA) IgA, and deaminated gliadin peptide (DGP) IgA and IgG serologies were obtained. Demographic data, screening frequency, and serological positivity were compared between AA and Ca patients by Student’s t test, Fischer’s exact test, and Chi-squared analysis with a significance level of p<0.05. Results: A total of 935 patients with T1D aged 18 years and younger were identified. Of the 798 patients with data on race, there were 380 AA and 405 Ca patients with T1D. There were no differences in mean age between AA and Ca, though AA patients were more commonly female (58.7% vs. 49.9%, p=0.015). The overall screening rate with any antibody test was 23.1%. Testing rates for TTG IgA (45/380 in AA vs. 180/405 in Ca, p<0.0001), EMA IgA (7/380 vs. 36/405, p<0.0001), DPG IgA (4/380 vs. 36/405, p<0.0001), and DGP IgG (4/380 vs. 34/405, p<0.0001) were all significantly lower in AA versus Ca. Positivity rates for TTG IgA (3/45 vs. 30/180, p=0.10), EMA IgA (0/7 vs. 13/36, p=0.08), DGP IgA (0/4 vs. 7/36, p=1.0), and DGP IgG (1/4 vs. 13/34, p=1.0) were not significantly different between the 2 groups. Conclusion: Despite recommendations to screen patients with T1D for CD, we found low screening rates in a pediatric T1D population overall. AA patients with T1D were significantly less likely to be screened than Ca patients. Interestingly, there were no differences in rates of serological positivity between AA and Ca, though this may be limited by a small sample size. Reasons for lower screening in AA T1D patients are not known but might be due to differences in perception of disease risk, symptomatology, lack of knowledge about screening recommendations, or referral bias. This study suggests the need for improvement in CD screening for pediatric patients with T1D and better estimates of CD prevalence in AA patients with T1D.

Enfermedad celíaca

Coeliac disease is a systemic autoimmune disorder that is triggered by the ingestion of gluten and associated prolamins in individuals with genetic susceptibility (mainly HLA), characterised by a variable combination of specific antibodies: gluten-dependent clinical manifestations, specific coeliac disease antibodies, HLA-DQ2 and/or DQ8 haplotype and enteropathy. The specific antibodies consist of anti-TG2 antibodies, including endomysial and deamidated gliadin peptide antibodies. In childhood and adolescence, the intestinal biopsy could be omitted in symptomatic subjects with anti-TG2-IgA antibody titres>10 times the cut-off point, verified by a positive antibodies endomysial and HLA-DQ2 and/or DQ8, and only in this case, the diagnosis could be made and treatment started with gluten-free diets. In all the rest of the cases, a first intestinal biopsy, before withdrawal of the gluten diet, is mandatory to prevent incorrect diagnoses.

Early Microbial Markers of Celiac Disease

Seroreactivity against the Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein (OmpW) has been detected in celiac disease patients with small-bowel mucosal atrophy. Levels of these antibodies decrease during a gluten-free diet, but their functions and time of appearance in celiac disease are not known. We aimed to search for evidence of possible microbial targets of the immune responses in the early-stage celiac disease patients who showed normal small-bowel mucosal architecture at the time of the first investigations, but later on a gluten-containing diet developed mucosal atrophy. Forty-four cases with proven early-stage celiac disease and normal mucosal morphology were enrolled. Patients' sera were tested for celiac disease antibodies against tissue transglutaminase (tTG-ab), endomysium, and for microbial antibodies against I2, OmpW, and ASCA IgG and IgA isotypes in both at the time of diagnosis and while on a gluten-free diet. Thirty-four (77%) of 44 patients with early-stage celiac disease had elevated serum antibodies to one or more of the antibodies ASCA, I2, and OmpW. Furthermore, 5 of 6 cases negative for both tTG-ab and endomysium showed positivity for the microbial markers. Seroreactivity to ASCA IgA, ASCA IgG, and OmpW decreased significantly during gluten-free diet. Seroreactivity to different microbial antigens is evident already in patients with early-stage celiac disease. ASCA antibodies seem to be gluten-dependent. The results indicate that the microbial targets might have a role in the early development of celiac disease.

Su1459 Characterization of Celiac Disease Antibody Response Reveals Wheat Non-Gluten Proteins As Novel Target Antigens

Su1459 Characterization of Celiac Disease Antibody Response Reveals Wheat Non-Gluten Proteins As Novel Target Antigens

Diagnostic Challenges in Celiac Disease

1. The most important challenge in diagnosis of celiac disease is not-performing the diagnostic tests in suspected persons. Because of multi-organ damage and multiple manifestations of disease, diagnosis of celiac disease may be delayed. It seems general physicians should be aware about uncommon presentations of disease and indications of celiac tests. 2. The second most important challenge is in patients with suspected disease but negative serologic tests. In these cases evaluating of HLA can be useful. 3. The third challenge is in cases with positive serologic tests but negative histopathological findings. There may be false positive serologic response or consumption of gluten before testing. We recommend introduction of gluten for at least 3 mo and re- endoscopy and if diagnosis is equivocal HLA-typing for DQ8 and DQ2 should be done. 4. The forth challenge is about performing endoscopy. Based on guideline from ESPGHAN if there are typical clinical manifestations of celiac disease, Anti-TTG more than ten times UPN, positive Anti-EMA and HLA DQ2, performing endoscopy may not be necessary, but many physicians don’t agree with this idea. 5. In people who are genetically predisposed to celiac disease antibody levels may be fluctuating thus endoscopy with biopsy should be done in these patients. 6. In children lower than 2years, Anti- TTG and Anti –EMA have low sensitivity. we recommend Anti-TTG and Anti-DGP in these patients. 7. Resolution of symptoms after gluten free diet is not necessarily a feature of celiac disease. This condition may be seen in patients with IBS or non-celiac gluten sensitivity.