Immunoglobulin A anti-tTG Research Articles

Redefining Celiac Iceberg in Children in North India—Do Asymptomatic Subjects Need Screening?

The prevalence of celiac disease (CD) in Indian children is not well documented, with most of the studies focusing on high-risk groups and not the general population. This study was conducted to determine the prevalence of CD in asymptomatic school children of Jaipur, Rajasthan. A cross- sectional study was conducted among healthy school children of Jaipur. Demographic data, symptoms, and signs including dermatological examination were recorded. The screening for CD was done by ELISA-based anti-tissue transglutaminase (tTG) immunoglobulin A (IgA) antibody testing. Children with high IgA anti-tTG underwent upper gastrointestinal endoscopy for small bowel biopsy from the second part of the duodenum. This study involved 575 subjects, out of which, 6 (1.04%) were found to be IgA tissue transglutaminase antibody (IgA-tTG) positive. All 6 subjects were found to be having changes consistent with celiac disease on duodenal biopsy. To conclude, the calculated prevalence of celiac disease was 1 in 96 subjects.

A celiac disease marker: Serum immunoglobulin a anti-tissue transglutaminase in vitiligo cases and controls in a hospital in South-West Nigeria

Background: Vitiligo is an autoimmune disorder resulting from the destruction of melanocytes of affected patients. Celiac disease (CD) is characterised by autoimmune inflammation of small intestinal mucosa specifically triggered by the gluten consumption in susceptible individuals. Immunoglobulin A (IgA) anti-tissue transglutaminase (anti-tTG) serology is recommended as an initial test for the diagnosis of CD prior to confirmation with intestinal biopsy. Aim: We aimed to compare the serum IgA anti-tTG levels in vitiligo patients and controls without vitiligo in a hospital in South-West Nigeria. Materials and Methods: The study was a case–control study of 33 vitiligo cases and 33 controls. IgA anti-tTG was assayed in participants’ sera using an enzyme-linked immunosorbent assay protocol employing recombinant human tTG. Results: A total of 66 participants were recruited into the study; 33 cases with vitiligo and 33 controls. The median age for cases was 50 years (range: 4–82). The median age for the controls was 55 years (range: 23–76). Generalised vitiligo accounted for 13 (40%) of vitiligo cases with the others consisting of various forms of segmental vitiligo. Anti-tTG levels were higher in cases at 6.1U/ml (8.8, 0.6–20.0) (med [interquartile range (IQR), min-max]), compared to controls 5.2 U/ml (3.7, 0.7–22.4). Difference between groups estimated using the Mann-Whitney U-test was not significant, u = 408.0, P = 0.08 (α = 0.05). Conclusion: There was no significant difference in serum IgA anti-tTG in vitiligo cases and controls in this study. Further studies are required to clarify the nature of the association between vitiligo and CD.

Adherence to Gluten-free Diet in a Celiac Pediatric Population Referred to the General Pediatrician After Remission.

Assessment of adherence to gluten-free diet in celiac disease (CD) is generally recommended. Few data are available about consequences of transition from the referral center to the general pediatrician (GP) once remission is achieved. Adherence was assessed in patients referred to the GP for an annual basis follow-up, called back for re-evaluation. Immunoglobulin A (IgA) antitissue transglutaminase (anti-tTG) antibodies and the Biagi score (BS) were determined at last follow-up at the referral center (V1), and at re-evaluation (V2). Patients were classified as adherent (BS 3-4, IgA anti-tTG <7 U/mL) and nonadherent (BS 0-2, IgA anti-tTG ≥7). Scores of adherence were correlated with personal and clinical data. We evaluated 200 patients. Overall, we found good adherence rates in 94.95% of patients at V1 and 83.5% at V2. IgA anti-tTG were negative in 100% at V1 and 96.97% at V2. BS is 3 to 4 in 94.5% at V1 and 84% at V2. Adherence at V2 was significantly worse than V1 (P < 0.001). No significant associations were found between scores of adherence and sex, symptoms and age at diagnosis, family history of CD, comorbidity, and diagnosis by endoscopy. Age 13 years or older represents a risk factor for lack of compliance at V1 (P = 0.02) and V2 (P = 0.04), and foreign nationality at V2 (P = 0.001). The BS, serology, and a clinical interview, integrated, are reliable tools for assessing pediatric adherence to gluten-free diet. We argue that referring patients to the GP after remission of CD is important, but the process must be improved and recommendations are required.

Chemiluminescent Immunoassay versus Enzyme Linked Immunosorbent Assays for IgA Anti-Tissue Transglutaminase Antibodies Assessment in Celiac Disease Children

Recent describing of atypical, silent and latent form of celiac disease (CD) increased the preocupation for screening methods.To perform a comparative study of immunoglobulin A (IgA) anti tissue-transglutaminase (tTG) antibodies (Ab) assessment using chemiluminescence versus Enzyme Linked Immunosorbent Assay (ELISA).The study included two lots.The first lot consisted in 35 biopsy confirmed CD children aged between two and 18 years.The control lot included 40 children with normal duodenal morphology on intestinal biopsy that underwent upper digestive endoscopy for different gastrointestinal symptoms.Serum samples were provided from all subjects for IgA measurement, IgA anti tTG and EMA assessment. Immulite 2500 Anti tTG IgA (Siemens Co, LA, USA) and ImmuLisa anti-hu tTG antibody IgA ELISA (Immco Diagnostics Inc, NY, USA) kits were used for tTG-Ab assessment. All children underwent HLA typing for DQ2/DQ8. The sensitivity for IgA tTG assessment was greater for chemiluminescence (93,3%) versus ELISA (86,6%), p[0,05, while specificity, positive and negative predictive value didn�t register significant differences. Statistical comparison of the two tested methods revealed a better sensitivity for chemiluminescence. Diagnosis algorithm optimisation may be obtained by associating IgA anti tTG-Ab assessment using chemiluminescence followed by EMA confirmation by indirect immunofluorescence for CD screening.

Increased mortality among men aged 50years old or above with elevated IgA anti-transglutaminase antibodies: NHANES III.

BackgroundImmunoglobulin A (IgA) antibodies to tissue transglutaminase (tTG) are the serologic test of choice for diagnosing celiac disease (CD). Our aim was to determine if elevated IgA anti-tTG were associated with increased mortality risk.MethodsStored serum samples of National Health and Nutrition Examination Survey (NHANES) III (1988–1992) were available for 6032 individuals aged 50 years old or above, which were screened for IgA anti-tTG, and if positive, for IgA endomysial antibodies. Mortality was determined from the National Death Index records through 2006. Hazard ratios were calculated through Cox proportional hazards regression.ResultsFrom a total of 6032, 85 participants tested positive for IgA anti-tTG (1.4 %) and 5947 tested negative. After a median follow-up of 13 years, IgA anti-tTG positive participants were at increased risk of death in both crude (HR = 1.68; 95 % CI = 1.30–2.18) and adjusted analyses (adjusted hazard ratio = 1.43; 95 % CI = 1.10–1.85) as compared to IgA anti-tTG negative participants. The excess mortality was restricted to IgA anti-tTG positive males (adjusted hazard ratio = 1.69 (95 % CI = 1.26–2.29), as opposed to a hazard ratio of 0.96 (95 % CI = 0.57–1.62) among IgA anti-tTG positive females. Although the most common cause of death in IgA anti-tTG positive participants was cardiovascular disease (36 %), the increased hazard ratio was only observed in respiratory cause of death as compared to IgA anti-tTG negative participants (adjusted hazard ratio = 5.11; 2.76–9.46).ConclusionMen aged 50 years old or above participants of NHANES III with elevated IgA anti-tTG antibodies had increased mortality risk. Elevated IgA anti-tTG antibodies could be a nonspecific marker of serious disease in older men.

Celiac disease detection rate in gastroenterological patients

To determine celiac disease detection rate in patients with digestive disease. A total of 318 gastroenterological patients admitted to be treated at the Central Research Institute of Gastroenterology in September to October 2012 were examined. The patients' age was 18 to 74 years (mean 51.5±16.4 years). Immunoglobulin A (IgA) and immunoglobulin G (IgG) anti-gliadin antibodies (AGA), IgA anti-tissue transglutaminase (anti-tTG) antibodies and IgG anti-tTG antibodies were determined. When the antibodies were elevated, esophagogastroduodenoscopy with duodenal biopsy was performed. Forty-one of the 318 patients were found to have higher AGA (12.9%); out of them IgA AGA were in 17 (5.35%) patients and IgG AGA were also in 17 (5.35%). Elevated levels of both antibodies (IgA AGA and IgG AGA) were seen in 7 (2.2%) patients. Overall, the detection rate of increased AGA levels was 12.9%. The antibodies were more commonly higher in patients with liver diseases (21.8%) and in those with inflammatory bowel diseases (21.6%). Both IgA anti-tTG, IgG anti-tTG and IgA AGA, IgG AGA were detected in 6 (1.9%) of the 318 patients. The diagnosis of celiac disease was verified by duodenal histological examination in 3 (0.94%) of the 318 patients. The celiac disease detection rate in gastroenterological patients was 0.94%.

Coeliac disease in irritable bowel syndrome (Rome III) in Southeast Iran

Background and study aimsIrritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder and coeliac disease (CD) is an auto-immune enteropathy that can mimic almost any functional GI disorder. Both IBS and coeliac disease share common symptoms. The aim of the present study was to estimate the prevalence of CD in patients with IBS and its sub-types. Patients and methodsIn this cross-sectional study (2008–2010), all consecutive patients with IBS who fulfilled the Rome III criteria attending the GI units in Zahedan (Southeast Iran) were included. Patients based on the sub-type of IBS were classified as diarrhoea-predominant irritable bowel syndrome (D-IBS), constipation-predominant irritable bowel syndrome (C-IBS) and alternating symptoms (mixed type). Immunoglobulin A (IgA) tissue transglutaminase (anti-tTG) was used to screen patients for CD. In the case of positive serologic test, duodenal biopsies were taken to confirm the diagnosis. ResultsA total of 364 (221 females and 143 males) patients with IBS were included. The mean±standard deviation (SD) age of patients was 37.4±12.4years. Twenty (5.5%) patients were found to have positive IgA anti-tTG. Main symptoms of patients were diarrhoea (11/20), bloating (10/20) and abdominal distension (6/20). Thirteen (10.5%) patients were found to have positive IgA anti-tTG among the D-IBS, two (1.6%) in the C-IBS and five (4.2%) in M-IBS groups. ConclusionThe prevalence of CD in IBS is high. IBS subjects whose main complaint is diarrhoea, bloating or even abdominal distension should be evaluated for CD.

Celiac disease in Portuguese children and adults with Down syndrome

Celiac disease (CD) affects up to 1% of the general population. Studies from several countries reported higher prevalence rates in Down syndrome (DS) patients. The aim of this study was to determine the CD prevalence in Portuguese DS patients. The study cohort consisted of 98 DS patients (58 male and 40 female, 1-45 years). Serological screening was performed using immunoglobulin A (IgA) anti-endomysium antibody (EMA), determined by an immunofluorescence assay with monkey esophagus as substrate, and IgA anti-tissue transglutaminase (tTG), measured by an enzyme-linked immunosorbent assay with tissue transglutaminase as antigen. The serologically positive patients were selected for upper endoscopy with biopsy procedure. The intestinal mucosa biopsy specimens were classified according to the Marsh criteria. Nineteen patients (19.4%), nine children and 10 adults, were positive for IgA EMA and 12 (12.2%), eight children and four adults, for IgA anti-tTG. All the IgA anti-tTG positive patients were simultaneously positive for IgA EMA. The histological findings (Marsh III) confirmed CD in nine of the remaining 17 patients who underwent endoscopy and biopsy - prevalence rate of 9.2%. All Marsh III patients were IgA EMA positive, but four Marsh III patients were IgA anti-tTG negative. DS Portuguese patients have a high CD prevalence rate. This study supports that, in our population, the current recommendations for CD screening in DS patients should be implemented and screening must be EMA based.

Positive predictive value of serological diagnostic measures in celiac disease

Celiac disease (CD) antibodies, immunoglobulin A (IgA) anti-tissue transglutaminase (anti-tTG), IgA endomysium antibody (EMA), IgA and IgG anti-gliadin antibodies (IgA and IgG AGA) are first-line diagnostic tools used in selecting patients for duodenal biopsy. The goal of this study was to evaluate the diagnostic quality of serological testing for CD. CD serological tests (IgA and IgG AGA, anti-tTG and EMA) from 11,915 individuals were measured. Data were combined with clinical data and results of duodenal biopsy using a unique Danish personal identification number. The positive predictive value (PPV) varied according to different combinations of positive CD antibodies, being highest when all antibodies were positive (97.6%). The anti-tTG concentration correlated strongly with EMA positivity, number of additional positive antibodies, and higher PPV. A logistic regression model predicted the probability of later biopsy-proven CD in relation to concentrations of IgA AGA and anti-tTG at initial serological screening. The anti-tTG concentration at initial serological CD screening was highly informative in relation to EMA positivity, number of additional CD specific antibodies and PPV. Furthermore, in the high-risk group of patients investigated, the concentrations of anti-tTG and IgA AGA at initial serological screening could accurately predict the probability of future biopsy-proven CD.

Questionnaire-Based Case Finding of Celiac Disease in a Population of 8- to 9-Year-Old Children

Antibody screenings and diagnosis of celiac disease (CD) among children with type 1 diabetes have suggested that a considerable proportion of children with CD may, in fact, have preclinical (undiagnosed) symptoms. We aimed to test if a questionnaire would lead to significant case finding in an unselected population of 8- to 9-year-old children. The study population included 9880 children aged 8 to 9 years. Before the study, 13 children from the study population were known to have CD. We developed a questionnaire on the basis of 5 simple items suggestive of CD and mailed the questionnaire to the families of all children in the study population who resided in the County of Funen, Denmark. In total, 7029 respondents returned the questionnaire (70%); among them, 2835 children had 1 or more symptoms. These children were invited for a blood test to determine their human serum immunoglobulin A (IgA) anti-tissue transglutaminase antibody (anti-tTG) levels. Of the 1720 children who were tested for the human serum IgA anti-tTG, 24 participants had a positive result (range: 20 to >150 U). Seventeen of these children underwent an upper endoscopy procedure. Fourteen children had histologic signs of CD (Marsh classification stage III). Fourteen children met the diagnostic criteria for CD. The prevalence proportion of patients who were newly diagnosed with CD was 0.14% (95% CI: 0.08-0.24) (14 of 9967), and the estimate of the minimum total prevalence proportion of children with CD was 0.27% (95% CI: 0.18-0.39) (27 of 9980). The maximal prevalence proportion of patients with newly diagnosed CD was 1.22% (95% CI: 0.76-1.90) (21 of 1720), including those participants who had a positive anti-tTG result but not a final diagnosis of CD. The ratio of known to minimally symptomatic CD was approximately 1:1. A number of preclinical and low-grade symptomatic patients with CD may be identified by their responses to a mailed questionnaire.

Prevalence of Celiac Disease in Egyptian Children Disputes the East–West Agriculture‐dependent Spread of the Disease

Celiac disease (CD) seems to be a common disorder in north Africa; however, to our knowledge no data are yet available on its prevalence in Egypt. This study was undertaken to investigate the frequency of CD in Egyptian children. We investigated a sample of the general pediatric population (1500 individuals, 656 girls and 844 boys, age range 7 months to 18 years, median age 8.0 years) (group A); 150 children (age range 6 months to 13 years, median age 16 months) admitted for diarrhea or failure to thrive (group B); and 250 children and adolescents with type 1 diabetes (group C). The screening test was serum class A anti-transglutaminase (anti-tTG) antibody; immunoglobulin A (IgA) antiendomysium, total IgA, and IgG anti-tTG, and small bowel biopsy was performed for confirmation of diagnosis. In group A, 8 of 1500 children fulfilled the criteria for CD diagnosis; the prevalence of CD was at least 1 in 187 individuals (0.53%; 95% CI 0.17%-0.89%). In group B, 7 of 150 children had CD (4.7%, 95% CI 1.4-7.9). In group C, 16 of 250 sera showed positive results to both the IgA anti-tTG and the IgA antiendomysium test (6.4%; 95% CI 3.4-9.4). Celiac disease is a frequent disorder among Egyptian children, both in the general population and in at-risk groups. Therefore, our data do not support the theory of a Middle East-Europe CD prevalence gradient secondary to the pattern of agriculture spreading from the so-called Fertile Crescent.

Is immunoglobulin A anti-tissue transglutaminase antibody a reliable serological marker of coeliac disease?

Anti-tissue transglutaminase (tTG) antibody is being used increasingly as a diagnostic tool in the serological investigation of coeliac disease. However, positive predictive values of immunoglobulin A (IgA) anti-tTG for coeliac disease in prospective studies have been disappointing and false-positive results are reported. To assess the clinical utility of cascade testing for anti-tTG and anti-endomysium antibody (AEA). Two unselected retrospective cohorts from routine diagnostic investigation for possible gluten sensitive enteropathy: group 1 comprised 57 cases seropositive for anti-tTG and group 2 comprised 52 cases seronegative for anti-tTG. In both groups, all cases had also undergone small-intestinal biopsy. Patients were assessed for the presence of IgA anti-tTG by enzyme-linked immunosorbent assay and for IgA AEA by immunofluorescence. The positive predictive value of IgA anti-tTG for biopsy-confirmed coeliac disease was 54%. The positive predictive value of dual positivity for anti-tTG and AEA was 97%. The negative predictive value of IgA anti-tTG was 100%. The data presented here support the use of IgA anti-tTG as an initial screen for coeliac disease. Coeliac disease is unlikely when IgA anti-tTG is absent. However, many false-positive results are seen, and clinical utility and diagnostic efficiency are improved markedly if positive results are confirmed with the more accurate, but labour-intensive, AEA assay.

Autoantibodies to tissue transglutaminase as predictors of celiac disease

Background & Aims: Immunoglobulin A (IgA) autoantibodies to endomysium (EMA) are highly specific and sensitive markers for celiac disease. Recently, we identified tissue transglutaminase (tTG) as the major if not sole endomysial autoantigen. Methods: An enzyme-linked immunosorbent assay (ELISA) was established to measure IgA anti-tTG titers in serum samples from 106 celiac patients with partial or subtotal villous atrophy, 43 celiac patients on a gluten-free diet, and 114 diseased and healthy controls. Results were correlated with clinical and histological data and with EMA titers. Results: In patients with biopsy-proven celiac disease consuming a normal, gluten-containing diet, 98.1% of the serum samples had elevated IgA titers against tTG, whereas 94.7% of the control sera were negative. IgA anti-tTG correlated positively with semiquantitative IgA EMA titers ( r = 0.862; P < 0.0001). Conclusions: An ELISA based on tTG allows diagnosis of celiac disease with a high sensitivity and specificity. IgA anti-tTG and IgA EMA show an excellent correlation, further confirming the enzyme as the celiac disease autoantigen. Because the assay is quantitative, not subjected to interobserver variation, and easy to perform, it will be a useful tool for population screening of a hitherto underdiagnosed disease. GASTROENTEROLOGY 1998;115:1317-1321