Study of the immune response in celiac patients with selective IgA deficiency who start a gluten-free diet.

Studies are scarce regarding IgG anti-tissue transglutaminase 2 (tTG) normalization in selective IgA deficient (SIgAD) celiac disease (CD) patients after beginning a gluten free diet (GFD). The aim of this study is to analyse the decreasing dynamics of IgG anti-tTG in patients diagnosed with CD who start a GFD. To achieve this objective, IgG and IgA anti-tTG levels at diagnosis and during follow-up in 11 SIgAD CD patients and in 20 IgA competent CD patients were retrospectively evaluated. At diagnosis, statistical differences were not found when comparing IgA anti-tTG levels of IgA competent subjects with IgG anti-tTG levels of SIgAD subjects. Regarding the decreasing dynamics, even though no statistical differences were found (p = 0.06), normalization rates were slower for SIgAD CD patients. After 1 and 2 years on GFD, respectively, only 18.2% and 36.3% of the SIgAD CD patients normalized IgG anti-tTG levels; otherwise, IgA anti-tTG reached values under the reference values in 30% and 80% of the IgA competent patients in the same time-points. Although IgG anti-tTG has demonstrated a high diagnostic efficiency in SIgAD CD pediatric patients, this test does not appear to be as precise for long-term GFD response monitoring as IgA anti-tTG levels in IgA sufficient patients.

Efficacy Study of Anti-Endomysium Antibodies for Celiac Disease Diagnosis: A Retrospective Study in a Spanish Pediatric Population.

The aim of this study was to assess the efficacy of anti-endomysium antibodies (EMA) as a serological marker for celiac disease (CD) diagnosis in a pediatric population. A retrospective study of pediatric patients who underwent a CD serological markers study: EMA and anti-tissue transglutaminase antibodies (anti-TG2). Clinical symptomatology, degree of histological lesion, human leukocyte antigen (HLA) haplotype compatible with CD (HLA DQ2 and/or DQ8), and final diagnosis were taken into account. We included 445 patients who were classified in two groups according to the final diagnosis. Group 1: 232 children with CD, 91.4% of whom exhibited small intestinal villous atrophy, 228 being EMA-positive and four EMA-negative. Group 2: 213 children with a non-CD diagnosis, 212 EMA negative and one EMA positive. Both antibodies, EMA and anti-TG2, reached similar sensitivities, 98% and 99% respectively, while EMA had a higher specificity (99%) than anti-TG2 (93%). By using both markers combined, compared to using anti-TG2 alone, 5.7% of patients are better diagnosed. However, when we compare the efficacy of EMA and anti-TG2 in asymptomatic and symptomatic patients, the sensitivity of EMA is 98% irrespective of symptoms, thus higher than for anti-TG2 ≥10 × upper limit of normal (ULN) (respectively 77% and 84%). Our results support the use of EMA to increase CD diagnostic accuracy in a non-biopsy approach, especially in asymptomatic children.

Prevalence of celiac disease serological markers in a cohort of Italian rheumatological patients.

AIM: To assess the prevalence of celiac disease (CD) serological markers in a cohort of patients referred to an Italian rheumatological outpatient clinic. BACKGROUND: Current guidelines do not suggest CD screening in patients with rheumatological diseases and these subjects are not considered to be at high risk for CD. METHODS: A total of 230 sera of rheumatological patients referred to the Division of Internal Medicine at the Department of Medical and Surgical Sciences between January 2005 and December 2013 were screened for CD by testing IgA antitransglutaminase (TTG IgA), IgG deamidated gliadin peptides (DGP IgG) and IgA antiendomysium (EMA) antibodies. Of the 230 patients tested, 67 had a diagnosis of rheumatoid arthritis (RA), 52 Sjögren's syndrome (SjS), 42 systemic sclerosis (SCL), 35 systemic lupus erythematosus (SLE), 15 mixed connective tissue disease, 11 polymyositis and 10 dermatomyositis. RESULTS: TTG IgA antibodies were identified in 7/230 cases (3%), 3 in SjS (3/42 - 5.8%), 2 in SCL (2/42 - 4.8%), 1 in RA (1/67 - 1.5%) and 1 in SLE sera (1/35 - 2.8%). All the seven sera were also positive for DGP IgG and EMA IgA. DGP IgG were the most frequent antibody detected, being found in 16 (7%) sera. CONCLUSION: This study identified a high prevalence of CD antibodies in adult patients referred to a rheumatology outpatient clinic. These results highlight the importance of CD screening in subjects presenting with rheumatological features.

Interpretation of serological tests in the diagnosis of celiac disease: Anti-deamidated gliadin peptide antibodies revisited.

Algorithms for celiac disease diagnosis provided by guidelines are based primarily on anti-tissue transglutaminase 2 (TG2) antibodies and/or anti-endomysium antibodies. The place of anti-deamidated gliadin peptide (DGP) antibodies is less well established. This study was designed to assess the clinical relevance of anti-DGP antibodies. Two thousand and twenty-six consecutive unselected patients systematically tested for anti-TG2, endomysium, gliadin, DGP antibodies and IgA dosage were investigated. The serological interpretation was assessed by analyzing the medical records of patients. From the 1984 newly investigated patients suspected of celiac disease, 10% had at least one celiac marker. Anti-TG2, anti-endomysium, anti-gliadin and anti-DGP antibodies were found in 1.1%, 0.6%, 6.8% and 4.1% of cases respectively, with different combinations. The diagnosis of celiac disease was retained in 0.45% of patients. When using the duodenal biopsies as a gold standard, analysis of the anti-DGP diagnosis performance showed that the specificity and the predictive positive value (PPV) were lower than that of the anti-TG2 assay. The combined detection of anti-TG2 and anti-DGP antibodies had a lower PPV than that of anti-TG2 and anti-endomysium antibodies (p = 0.04). When analyzing the contribution of anti-DGP antibodies as an additional marker to both anti-TG2 and anti-endomysium antibodies, the PPV of the three associated antibodies was shown to be significantly lower than the PPV of the both anti-TG2 and anti-endomysium antibodies (p = 0.04). As a conclusion, anti-DGP antibodies may not have the diagnosis value required as an additional screening test to anti-TG2 antibodies for identifying celiac disease patients in medical centers where anti-endomysium detection is available.

Screening of celiac disease in children with Henoch-Schoenlein purpura.

Prevalence of celiac disease (CD) is 2.42 % in healthy Turkish children. The frequency of IgA-associated disorders is increased in CD. Henoch-Schoenlein purpura (HSP) is an IgA-associated vasculitis. Association of HSP with CD has not been evaluated. We aimed to evaluate whether CD prevalence is increased in children with HSP. Children with HSP were evaluated for demographic, anthropometric, clinical, and laboratory data including urinalysis, complete blood count, albumin, creatinine, and IgA levels. In addition, tTG-IgA, EMA-IgA, anti-DGP-IgA, and IgG antibody levels were measured. Seropositive patients were evaluated by endoscopic small bowel biopsy. The rate of CD seropositivity and confirmed CD in HSP patients was compared to the rate in healthy Turkish children. There were 42 children (25 male) with HSP. No patient had classical CD symptoms, but two patients had growth failure. None of them had IgA deficiency, anemia or hypoalbuminemia. Celiac serology was positive in five (12 %) children. Endoscopic evaluation was performed in four patients, and two (5 %) of them were confirmed to have CD. Prevalence of both CD seropositivity and histologically confirmed CD in children with HSP was significantly higher compared to healthy Turkish children (p < 0.001 and p = 0.019, respectively). CD seropositivity rate in children with HSP (12 %) is significantly higher than the rate in healthy children. Although the number of children with HSP is small in this preliminary study, this result suggests that celiac screening may be considered in children with HSP.

Fully-automated, chemiluminescence IgA and IgG anti-tissue transglutaminase (tTG) antibodies serum assays for the screening of celiac disease.

AIM: Celiac disease (CD) is a systemic immune-mediated enteropathy sustained by gluten ingestion in genetically susceptible subjects. The European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) has recently revised the diagnostic criteria, emphasizing the crucial role of serological testing in the diagnosis of this condition. This study was hence aimed to evaluate a new chemiluminescence assay for measuring anti-transglutaminase (tTG) and anti-endomysium (EMA) antibodies in a general population of unselected outpatients. MATERIALS AND METHODS: The IgA and IgG anti-tissue transglutaminase (tTG) antibodies (Quanta Flash® IgA and Quanta Flash® IgG tTG, Inova Diagnostics, San Diego, CA, USA) were measured with the fully-automated BIO-FLASH® analyzer (Inova Diagnostics) in serum samples of 727 consecutive patients without a diagnosis of CD. Data were compared with those of anti-endomysium antibody (EmA) obtained in the same population. RESULTS: A total of 96.4% samples display a negative concordance (anti-tTG negative and EMA negative), O% were positive for EMA and negative for anti-tTG IgA and IgG, 3.6% were both positive for tTG IgA and EMA, whereas 0.6% displayed discordant results (positive for anti-tTG and negative for EMA). The concordance (99%) and inter-rater agreement (Kappa Statistics, 0.943; p<0.001) between anti-tTG IgA and EmA antibodies were excellent, with sensitivity and specificity of 99% and 100%, respectively. CONCLUSION: The results of this study show that Quanta Flash® IgA assay alone may be regarded as a reliable approach for screening of CD, with no need to perform EMA detection.

Central America in Transition: From Maize to Wheat Challenges and Opportunities.

The Central American countries: Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, and Panama are in transition from a dietary culture based mainly on maize to a wheat-containing diet. Several other changes are occurring, such as a decrease of parasitic and infectious diseases. The environmental changes permit a prediction of an increase of celiac disease and other autoimmune diseases such as type I diabetes and thyroid disease in these genetically heterogeneous countries. At present, celiac disease and gluten-related disorders are considered to be of no relevance at the level of public health in these nations. This review documents the presence of celiac disease in Central America. It draws attention to some of the challenges in planning systematic studies in the region since up until recently celiac disease was unknown. The aim of this review is to disseminate knowledge obtained with preliminary data, to stimulate clinical and basic scientists to study these diseases in Central America and to alert authorities responsible for the planning of education and health, to find possibilities to avoid a rise in these disorders before the epidemics start, as has occurred in the Mediterranean countries.

Adaptive diagnosis of coeliac disease.

Coeliac disease has for a long time simply been regarded as a gluten-dependent enteropathy and a duodenal biopsy was required in all patients for the diagnosis. It is now accepted that autoimmunity against transglutaminase 2 is an earlier, more universal and more specific feature of coeliac disease than histologic lesions. Moreover, high serum levels of combined anti-transglutaminase 2 and anti-endomysium antibody positivity have excellent predictive value for the presence of enteropathy with villous atrophy. This makes the histology evaluation of the gut no longer necessary in well defined symptomatic paediatric patients with compatible HLA-DQ2 and/or DQ8 background. The biopsy-sparing diagnostic route is not yet recommended by gastroenterologists for adults, and certain clinical circumstances (immunodeficiency conditions, extraintestinal manifestations, type-1 diabetes mellitus, age less than 2 years) may require modified diagnostic approaches. Coeliac patients with preserved duodenal villous structure do exist and these need a more extended evaluation by immunologic and molecular biology tools.

Overview of biomarkers for diagnosis and monitoring of celiac disease.

Among the adverse reactions caused by wheat, celiac disease (CD) is the longest studied and best-known pathology. The more recently defined non-celiac gluten sensitivity (NCGS) presents with symptoms which are often indistinguishable from CD. Diagnosis of CD is based on serologic, molecular, and bioptic testing. The IgA anti-transglutaminase (tTG) test is considered highly important, as it shows high sensitivity and specificity and its levels correlate to the degree of intestinal damage. Small bowel biopsy can be avoided in symptomatic patients with IgA anti-tTG levels above 10× the manufacturer's cut-off. Recently, tests of anti-deamidated peptides of gliadin (DGP) have replaced classic anti-native gliadin (AGA) tests. DGP assays have a considerably higher diagnostic accuracy than AGA assays, especially in the IgG class, and can replace anti-tTG tests in patients with selective IgA deficiency. The combination of IgG anti-DGP plus IgA anti-tTG assays show greater sensitivity than a single test, with very high specificity. EMA tests have great diagnostic accuracy but are not recommended by all the latest guidelines because they are observer dependent. Biopsy must still be considered the gold standard for CD diagnosis. HLA-DQ genotyping can be used to screen asymptomatic children and in cases of histology/serology disagreement. About half of NCGS patients are DQ2 positive and have IgG AGA. To diagnose NCGS, first CD and wheat allergy must be excluded; then the wheat dependence of symptoms must be verified by a gluten-free diet and subsequent gluten challenge.

Celiac disease diagnosis: impact of guidelines on medical prescription in France.

OBJECTIVE: Celiac disease is a complex autoimmune disease affecting patients of any age, who may present a wide variety of clinical manifestations. Different guidelines for the diagnosis and management of celiac disease have been recently published. The aim of this study was to determine whether the recommendations issued in these guidelines have been adopted by physicians in France when celiac disease was suspected. METHODS: A total of 5521 physicians were asked to fill in a detailed questionnaire on diagnosing celiac disease to evaluate their medical practice, as to the type of symptoms leading to the suspicion of celiac disease, the prescription of duodenal biopsy or serological tests, the type of serological tests (anti-tissue transglutaminase, anti-endomysium, anti-gliadin and anti-reticulin antibodies, total immunoglobulin A measurement) prescribed to diagnose celiac disease. RESULTS: The analysis of the responses of 256 general practitioners (GPs), 221 gastroenterologists and 227 pediatricians showed that the protean clinical presentations of celiac disease might be better recognized by gastroenterologists and pediatricians than by GPs. Gastroenterologists asked for duodenal biopsy much more often than GPs and pediatricians when celiac disease was suspected. Serological testing and knowledge of critical markers, prescribed to diagnose celiac disease, differed among GPs, gastroenterologists and pediatricians. CONCLUSION: Analysis of medical prescriptions showed that the recommendations for celiac disease diagnosis are not necessarily followed by physicians, emphasizing the fact that the impact of national or international guidelines on medical behavior should be evaluated.

Sensibilidad y especificidad de los marcadores serológicos para diagnóstico y seguimiento de la condición celíaca / Sensitivity and specificity of serological markers for diagnosis and monitoring of celiac condition

Introducción: El diagnóstico precoz y seguimiento de la condición celíaca ha sido objeto de importantes cambios, y según la guía ESPGHAN (2012) la serología es ahora una herramienta fundamental. Los principales son los anticuerpos anti-gliadina IgG/IgA, anti-transglutaminasa IgG/IgA, anti-endomisiales (EMA), y los recientemente descritos anti-péptidos deaminados de gliadina (anti-DGPs). El propósito del estudio fue determinar la sensibilidad y especificidad de estos marcadores en 308 individuos con y sin patología. Materiales y métodos: A cada individuo se le realizaron determinaciones de: TTGG y TTGA Qual (AESKU Diagnostics ®, Germany), TgTG, TgTA, AAGG y AAGA por ENEASYSTEM III® (Byogenetix, Italia), Neoep. IgG/A (AESKU Diagnostics®, Germany), EMA IgG e IGA y GAF3X IgG e IgA (Euroimmun, Germany ®). Resultados: Los valores de sensibilidad (S) y especificidad (E) fueron: Para anti-IgA Celicheck: S: 44.44%, E: 97.59%; anti-TTG Qual: S: 14.28%, E: 97.61%; anti-neoepítopes IgG/IgA: S: 54.44%, E: 91.59%; AAG IgG: S: 89.11%, E: 63.19%; AAG IgA: S: 79.11%, E: 68.16%; anti-DGPs IgA: S: 86.67%, E: 96.21% (p<0,05). Conclusiones: Los ATgT IgG e IgA solo son superados por los anti-DGPs. Se debe ampliar las investigaciones para estandarizar este nuevo método de valoración.

Introduction: The diagnosis and management of celiac disease has undergone significant changes, according to the ESPGHAN guide (2012) serology is now an essential tool. The main ones are the anti-gliadin IgG/IgA anti-transglutaminase IgG/IgA, anti-endomysial and the recently described anti-deaminated gliadin peptides (anti-DGPs). The purpose of the study was to determine the sensitivity and specificity of these markers in 308 individuals with and without pathology. Materials and Methods: Each individual is simultaneously made the following determinations: TTGG and TTGA Qual (AESKU Diagnostics®, Germany), TgTG, TgTA, AAGG and AAGA ENEASYSTEM III® (Byogenetix, Italia), Neoep. IgG/A (AESKU Diagnostics®, Germany), EMA IgG, IGA and GAF3X IgG-IgA (Euroimmun, Germany®). Results: The sensitivity (S) and specificity (Sp) were: anti-IgA To Celicheck: S: 44.44%, E: 97.59% anti-TTG Qual: S: 14.28%, E: 97.61% anti-neoepitopes IgG/IgA: S: 54.44%, E: 91.59%; AAG IgG: S: 89.11%, E: 63.19%; AAG IgA: S: 79.11%, E: 68.16% IgA anti-DGPs: S: 86.67% E: 96.21% (p<0.05). Conclusions: IgG and IgA ATGT are surpassed only by anti-DGPs However, it is important to extend the research to standardize this new method of assessment.

[Immunological screening and follow-up of celiac disease: experience of the University Hospital of Marseille]. / Dépistage et suivi immunologique de la maladie cœliaque : expérience du CHU de Marseille.

PURPOSE: Anti-tissue transglutaminase antibodies (ATTG) have helped to distinguish atypical and silent clinical forms of celiac disease (CD). Immunological diagnosis or follow-up of the disease is now based in France in first line upon IgA ATTG serum evaluation. In the University Hospital of Marseille, the serological diagnosis of CD had consisted during several years in simultaneous determination of both IgA anti-endomysial antibodies (AEA) and IgA ATTG. In literature, few studies focused on the concordance between the two tests and a very few epidemiological data about CD in France are available. METHODS: Five thousand nine hundred and eighty-one patients for whom both AEA and ATTG testing were available were retrospectively included. Characteristics of this cohort were detailed. We numbered and analyzed especially bioclinical charts from patients with AAE/AATG discordance. RESULTS: Among our patients, all ages and all medical subspecialties were represented. Eighty-five new cases of CD were identified. Among the 6516 serum evaluations performed, only 31 tests were discordant. CONCLUSIONS: Our data give information about CD epidemiology in France. They support the contention that ATTG have to be evaluated in first line for CD diagnosis.

Diagnostic utility of coeliac disease: a descriptive study in a tertiary care hospital, oman.

OBJECTIVES: The prevalence of coeliac disease in Oman is unknown. We aim to estimate the prevalence of coeliac disease in at-risk subjects, describe the clinical characteristics and laboratory findings associated with coeliac disease and the validity of serological testing for coeliac disease at the Royal Hospital, Oman over a period of three years. METHODS: This is a retrospective case finding study. The medical and laboratory records were reviewed for patients for whom serum antiendomysium IgA antibodies were requested at the Royal Hospital during a 3-year period (1(st) Jan 2006-31(st) Dec 2008). The data were extracted in order to assess the following: a) Prevalence rate of coeliac disease among at-risk subjects; b) Clinical characteristics in patients with coeliac disease and clinical manifestations for which the requesting clinicians considered coeliac disease as a possible diagnosis, including their specialties; c) Laboratory tests results in patients with coeliac disease; and d) Validity of antiendomysium antibodies testing in comparison with histopathology of jejunal biopsies for diagnosing coeliac disease. RESULTS: The study included 431 patients (250 females, 181 males) who were suspected of having (or screened for) coeliac disease. The median of age was 15 years (range: 9 months-74 years) with mean ± SD 18.95 ± 14.1 years. Of these, 15 (3.5%) patients (10 females, 5 males) with a median age of 19 years and mean 21.4 ± 13.0 years (range: 2.5-38 years), had positive antiendomysium antibodies results with median (range) of 160 (40-320) IU/L and mean± SD 204.5 ± 160 IU/L. Of these 15 patients, 13 had positive jejunal histopathological changes indicative of coeliac disease; the remaining 2 patients had no biopsy examination. Of the 44 patients with negative antiendomysium antibodies <10 IU/L who had jejunal biopsy, 41 were negative and 3 had histopathological changes suggestive of mild coeliac disease. All the 3 patients had serum total IgA levels within the reference range. The calculated validity indicators for antiendomysium antibodies were: sensitivity 81.3%, specificity 100%, positive predictive value 100%, negative predictive value 93.2% and efficiency 94.7%. The most common mode of presentation in patients with coeliac disease was gastrointestinal features, type 1 diabetes mellitus, anemia, short stature and hypothyroidism. The seropositivity in tye 1 diabetics was 4.9%. Investigations for coeliac disease were most frequently made by endocrinologists (pediatric and adult) who accounted for 53.8% followed by gastroenterologists (pediatric and adult) with 40.6% with less consideration by the other clinicians (5.6%). CONCLUSION: The availability of highly specific and sensitive serological test and increased awareness for coeliac disease among some medical specialties has increased the number of diagnosed cases of coeliac disease. The requesting for serological test is being made mainly by endocrinologists and gastroenterologists.

Gliadin does not induce mucosal inflammation or basophil activation in patients with nonceliac gluten sensitivity.

BACKGROUND & AIMS: Nonceliac gluten-sensitive (NCGS) patients report intestinal and extra-intestinal symptoms shortly after ingesting gluten; these symptoms disappear on gluten-free diets, although these patients have no serologic markers of celiac disease or intestinal damage. In fact, there is no evidence for mucosal or serologic modifications in those individuals. We investigated immunologic responses of duodenal mucosa samples and peripheral blood basophils, isolated from NCGS patients, after exposure to gliadin. METHODS: Participants underwent a complete clinical evaluation to exclude celiac disease while on a gluten-containing diet, a skin prick test to exclude wheat allergy, and upper endoscopy (n = 119) at 2 tertiary medical centers in Italy. Patients were considered to have NCGS based on their symptoms and the current definition of the disorder. Subjects were assigned to the following groups: patients with celiac disease on gluten-free diets (n = 34), untreated patients with celiac disease (n = 35), patients with NCGS (n = 16), or controls (n = 34). Duodenal biopsy samples collected during endoscopy were incubated with gliadin peptides, and levels of inflammatory markers were assessed. Peripheral blood basophils were extracted and incubated with gliadin peptides or a mix of wheat proteins; activation was assessed based on levels of CD203c, CD63, and CD45. RESULTS: Duodenal mucosa samples collected from 69 patients with celiac disease showed markers of inflammation after incubation with gliadin. Some, but not all, markers of inflammation were detected weakly in biopsy samples from 3 controls and 3 NCGS patients (P = .00 for all markers). There were no significant increases in the levels of CD63 and CD203c in NCGS patients. CONCLUSIONS: Unlike the duodenal mucosa from patients with celiac disease, upon incubation with gliadin, mucosa from patients with NCGS does not express markers of inflammation, and their basophils are not activated by gliadin. The in vitro gliadin challenge therefore should not be used to diagnose NCGS.

Tissue transglutaminase levels above 100 U/mL and celiac disease: a prospective study.

AIM: To investigate whether a tissue-transglutaminase antibody (tTGA) level ≥ 100 U/mL is sufficient for the diagnosis of celiac disease (CD). METHODS: Children suspected of having CD were prospectively included in our study between March 2009 and September 2011. All patients with immune globulin A deficiency and all patients on a gluten-free diet were excluded from the study. Anti-endomysium antibodies (EMA) were detected by means of immunofluorescence using sections of distal monkey esophagus (EUROIMMUN, Luebeck, Germany). Serum anti-tTGA were measured by means of enzyme-linked immunosorbent assay using human recombinant tissue transglutaminase (ELiA Celikey IgA kit Phadia AB, Uppsala, Sweden). The histological slides were graded by a single experienced pathologist using the Marsh classification as modified by Oberhuber. Marsh II and III lesions were considered to be diagnostic for the disease. The positive predictive values (PPVs), negative predictive values (NPVs), sensitivity and specificity of EMA and tTGA along with their 95% CI (for the cut off values > 10 and ≥ 100 U/mL) were calculated using histology as the gold standard for CD. RESULTS: A total of 183 children were included in the study. A total of 70 (38.3%) were male, while 113 (61.7%) were female. The age range was between 1.0 and 17.6 years, and the mean age was 6.2 years. One hundred twenty (65.6%) patients had a small intestinal biopsy diagnostic for the disease; 3 patients had a Marsh II lesion, and 117 patients had a Marsh III lesion. Of the patients without CD, only 4 patients had a Marsh I lesion. Of the 183 patients, 136 patients were positive for EMA, of whom 20 did not have CD, yielding a PPV for EMA of 85% (95% CI: 78%-90%) and a corresponding specificity of 68% (95% CI: 55%-79%). The NPV and specificity for EMA were 91% (95% CI: 79%-97%) and 97% (95% CI: 91%-99%), respectively. Increased levels of tTGA were found in 130 patients, although only 116 patients truly had histological evidence of the disease. The PPV for tTGA was 89% (95% CI: 82%-94%), and the corresponding specificity was 78% (95% CI: 65%-87%). The NPV and sensitivity were 92% (95% CI: 81%-98%) and 97% (95% CI: 91%-99%), respectively. A tTGA level ≥ 100 U/mL was found in 87 (47.5%) patients, all of whom were also positive for EMA. In all these 87 patients, epithelial lesions confirming CD were found, giving a PPV of 100% (95%CI: 95%-100%). The corresponding specificity for this cut-off value was also 100% (95% CI: 93%-100%). Within this group, a total of 83 patients had symptoms, at least gastrointestinal and/or growth retardation. Three patients were asymptomatic but were screened because they belonged to a group at risk for CD (diabetes mellitus type 1 or positive family history). The fourth patient who lacked CD-symptoms was detected by coincidence during an endoscopy performed for gastro-intestinal bleeding. CONCLUSION: This study confirms based on prospective data that a small intestinal biopsy is not necessary for the diagnosis of CD in symptomatic patients with tTGA ≥ 100 U/mL.

Prevalence of celiac disease among blood donors in São Paulo: the most populated city in Brazil

OBJECTIVE: Celiac disease is a permanent enteropathy caused by the ingestion of gluten, which leads to an immunemediated inflammation of the small intestine mucosa. The prevalence of celiac disease varies among different nations and ethnic backgrounds, and its diversity is determined by genetic and environmental factors. São Paulo city is one of the largest cities in the world, with a vast population and an important history of internal migratory flow from other Brazilian regions, as well as immigration from other, primarily European, countries, resulting in significant miscegenation. The aim of the present study was to estimate the prevalence of adults with undiagnosed celiac disease among blood donors of São Paulo by collecting information on the ancestry of the population studied. METHODS: The prevalence of celiac disease was assessed by screening for positive IgA transglutaminase and IgA endomysium antibodies in 4,000 donors (volunteers) in the Fundação Pró-Sangue Blood Center of São Paulo, São Paulo, Brazil. The antibody-positive subjects were asked to undergo a small bowel biopsy. RESULTS: Of the 4,000 subjects, twenty-four had positive tests, although both antibody tests were not always concordant. For example, ten subjects were positive for IgA tissue transglutaminase only. In twenty-one positive patients, duodenal biopsies were performed, and the diagnosis of celiac disease was confirmed in fourteen patients (Marsh criteria modified by Oberhuber). In this group, 67% claimed to have European ancestry, mainly from Italy, Portugal and Spain. CONCLUSION: The prevalence of celiac disease is at least 1:286 among supposedly healthy blood bank volunteers in São Paulo, Brazil.

Eficacia del cordón umbilical humano como sustrato para detección de anticuerpos anti endomisio / Efficiency of human umbilical cord as substrate or detection of antiemdomysium antibodies / Aeficácia do cordão umbilical humano como substrato para a detenção de anticorpos anti-endomísio

Los anticuerpos anti endomisio IgA (EMA) están dirigidos hacia antígenos del tejido conectivo que rodea a las fibras del músculo liso. El objetivo de este trabajo fue evaluar la eficacia del cordón umbilical humano (CUH) como sustrato para detectar EMA mediante inmunofluorescencia indirecta y compararlo con una de las metodologías disponibles comercialmente, la cual utiliza como sustrato esófago de mono. Se obtuvieron 100 sueros de pacientes con diagnóstico de enfermedad celíaca y 50 sueros de pacientes clínicamente sanos con biopsia de mucosa intestinal normal, los cuales realizaron su consulta y atención en el Hospital Privado Centro Médico de Córdoba, en un periodo de tiempo comprendido entre los años 2006 y 2009. Los resultados obtenidos mostraron una "muy buena" concordancia entre ambos métodos. Se estimó para el método que utiliza CUH una sensibilidad y especificidad de 98% (93-99%) y 100% (93-100%) respectivamente con una eficacia del 99%. De acuerdo con lo anterior se concluye que utilizar CUH como sustrato para evaluar la presencia de EMA es confiable y efectivo para detectar pacientes con enfermedad celíaca no tratada.

The antiendomysium antibodies (EMA) are directed toward antigens of connective tissue that surrounds the smooth muscle fibers. The aim of this study was to evaluate the efficiency of human umbilical cord (HUC) as substrate to detect EMA by indirect immunofluorescence and to compare it with one of the commercially available methodologies which use monkey esophagus as substrate. Serum samples obtained from 100 patients with celiac disease diagnosis and 50 healthy controls with normal intestinal mucosa were evaluated. Patients were treated at the Hospital Privado Centro Médico de Córdoba over a period of time between 2006 and 2009. The results showed an "almost perfect" concordance between both methods. The calculated sensitivity and specificity for HUC was 98% (93-99%) and 100% (93-100%) respectively, with an efficiency of 99%. This results indicate that the use of HUC as substrate to evaluate the presence of EMA is reliable and effective for the detection of patients with untreated celiac disease.

Os anticorpos anti-endomísio IgA (EMA) são direcionados contra os antígenos do tecido conectivo que cercam as fibras do músculo liso. O objetivo deste trabalho foi avaliar a eficácia do cordão umbilical humano (CUH) como substrato para detectar EMA através da imunofluorescência indireta e compará-lo com uma das metodologias disponíveis comercialmente, a qual utiliza como substrato esôfago de macaco. Foram obtidos 100 soros de pacientes com diagnóstico de doença celíaca e 50 soros de pacientes clinicamente saudáveis com biópsia de mucosa intestinal normal, os quais realizaram sua consulta e atendimento no Hospital Privado Centro Médico de Córdoba, em um período de tempo compreendido entre os anos 2006 e 2009. Os resultados obtidos mostraram uma "ótima" concordância entre ambos os métodos. Foi calculada para o método que utiliza CUH uma sensibilidade e especificidade de 98% (93-99%) e 100% (93-100%) respectivamente com uma eficácia de 99%. De acordo com o acima exposto, se conclui que utilizar CUH como substrato para avaliar a presença de EMA é confiável e eficaz para detectar pacientes com doenças celíacas não tratadas.

Eficacia del cordón umbilical humano como sustrato para detección de anticuerpos anti endomisio / Efficiency of human umbilical cord as substrate or detection of antiemdomysium antibodies / Aeficácia do cordÒo umbilical humano como substrato para a detenþÒo de anticorpos anti-endomísio

Los anticuerpos anti endomisio IgA (EMA) están dirigidos hacia antígenos del tejido conectivo que rodea a las fibras del músculo liso. El objetivo de este trabajo fue evaluar la eficacia del cordón umbilical humano (CUH) como sustrato para detectar EMA mediante inmunofluorescencia indirecta y compararlo con una de las metodologías disponibles comercialmente, la cual utiliza como sustrato esófago de mono. Se obtuvieron 100 sueros de pacientes con diagnóstico de enfermedad celíaca y 50 sueros de pacientes clínicamente sanos con biopsia de mucosa intestinal normal, los cuales realizaron su consulta y atención en el Hospital Privado Centro Médico de Córdoba, en un periodo de tiempo comprendido entre los años 2006 y 2009. Los resultados obtenidos mostraron una "muy buena" concordancia entre ambos métodos. Se estimó para el método que utiliza CUH una sensibilidad y especificidad de 98% (93-99%) y 100% (93-100%) respectivamente con una eficacia del 99%. De acuerdo con lo anterior se concluye que utilizar CUH como sustrato para evaluar la presencia de EMA es confiable y efectivo para detectar pacientes con enfermedad celíaca no tratada.(AU)

The antiendomysium antibodies (EMA) are directed toward antigens of connective tissue that surrounds the smooth muscle fibers. The aim of this study was to evaluate the efficiency of human umbilical cord (HUC) as substrate to detect EMA by indirect immunofluorescence and to compare it with one of the commercially available methodologies which use monkey esophagus as substrate. Serum samples obtained from 100 patients with celiac disease diagnosis and 50 healthy controls with normal intestinal mucosa were evaluated. Patients were treated at the Hospital Privado Centro Médico de Córdoba over a period of time between 2006 and 2009. The results showed an "almost perfect" concordance between both methods. The calculated sensitivity and specificity for HUC was 98% (93-99%) and 100% (93-100%) respectively, with an efficiency of 99%. This results indicate that the use of HUC as substrate to evaluate the presence of EMA is reliable and effective for the detection of patients with untreated celiac disease.(AU)

Os anticorpos anti-endomísio IgA (EMA) sÒo direcionados contra os antígenos do tecido conectivo que cercam as fibras do músculo liso. O objetivo deste trabalho foi avaliar a eficácia do cordÒo umbilical humano (CUH) como substrato para detectar EMA através da imunofluorescÛncia indireta e compará-lo com uma das metodologias disponíveis comercialmente, a qual utiliza como substrato es¶fago de macaco. Foram obtidos 100 soros de pacientes com diagnóstico de doenþa celíaca e 50 soros de pacientes clinicamente saudáveis com biópsia de mucosa intestinal normal, os quais realizaram sua consulta e atendimento no Hospital Privado Centro Médico de Córdoba, em um período de tempo compreendido entre os anos 2006 e 2009. Os resultados obtidos mostraram uma "ótima" concordÔncia entre ambos os métodos. Foi calculada para o método que utiliza CUH uma sensibilidade e especificidade de 98% (93-99%) e 100% (93-100%) respectivamente com uma eficácia de 99%. De acordo com o acima exposto, se conclui que utilizar CUH como substrato para avaliar a presenþa de EMA é confiável e eficaz para detectar pacientes com doenþas celíacas nÒo tratadas.(AU)