Deamidated Gliadin Peptide Antibodies Research Articles

Diagnostic Accuracy of Tissue Transglutaminase and Combined Assay of Tissue Transglutaminase and Deamidated Gliadin Peptide in Children with Coeliac Disease: A Cross-sectional Study

Introduction: Coeliac Disease (CD) is a systemic immune disorder caused by gluten in genetically susceptible individuals. A serological screening assay for CD has been designed to detect Immunoglobulin A (IgA) and IgG anti-tissue Transglutaminase (a-tTG) and IgA and IgG Deamidated Gliadin Peptide antibodies (a-DGP) simultaneously. The seronegative gap can be closed when these two antigens are combined on a single solid phase. This is primarily because untreated CD children who are negative for antibodies of one of the antigens may exhibit a positive result for the other. Aim: To determine the diagnostic parameters {sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV)} of tTG-IgA and htTG-DGP (Coeliac fusion- a combination of IgA and IgG to human tTG and synthetic DGP) for the diagnosis of CD in clinically symptomatic children. Materials and Methods: This cross-sectional study was conducted at the Paediatric Outpatient Department (OPD) of Santokhba Durlabhji Memorial Hospital, Jaipur, Rajasthan, India from April 2023 to November 2023. The study population comprised 45 children (age >6 months and <18 years) showing clinical features of CD. Considering biopsy as the gold standard, the diagnostic parameters (sensitivity, specificity, PPV, NPV) of tTG-IgA and htTG-DGP were calculated with a 95% confidence interval for both tests. To determine the agreement between the two tests, Cohen’s kappa was calculated. A p-value less than 0.05 was considered statistically significant. Results: Out of the study population, 23 (46%) CD patients were in the age group of 3-6 years, while 13 (26%) patients were in the age group of 6-9 years. A total of 24 (53.3%) CD patients were males, and 21 (46.7%) were females. Chronic diarrhoea was the most common clinical feature in 31 (62%) patients. Considering duodenal biopsy as the gold standard, the study results showed that the anti tTG-IgA antibody test had a sensitivity of 91.1%, specificity of 80%, PPV of 97.6, and NPV of 50%. In comparison, the htTG-DGP antibody test had a sensitivity of 95.6%, specificity of 100%, PPV of 100%, and NPV of 71.43%. Conclusion: Currently, tTG-IgA is considered the best CD screening test. However, the inclusion of DGP IgG could increase diagnostic sensitivity, and a Combined IgA/G-DGP/ tTG assay could be even better than tTG-IgA for the diagnosis of childhood CD.

Performance of deamidated gliadin peptide antibodies as first screening for celiac disease in the general pediatric population

Performance of deamidated gliadin peptide antibodies as first screening for celiac disease in the general pediatric population

MO236: Serological Markers of Celiac Disease in Patients With IGA-Nephropathy: Prevalence and Diagnostic Significance

Abstract BACKGROUND AND AIMS It is known that IgA-nephropathy (IgAN) can be secondary to liver disease, skin disease, lung disease, etc. There is also evidence of an association between IgAN and celiac disease. In the Russian population, there are no studies aimed at identifying the prevalence of IgAN and celiac disease in adult. The aim of this study was to determine the incidence of celiac antibody (СА) in patients with IgAN and to compare the clinical and laboratory features within groups. METHOD fifty patients with IgAN were included in the study. Of these, 46 (92%) were male and 4 (8%) were female, ranging in age from 18 to 63 years. The mean age was 35.9 ± 9.8 years. All patients underwent general clinical blood and urinalysis, daily urinary protein excretion. Serum concentrations of IgA, total protein, albumin, creatinine, urea, uric acid, IgA antibodies to tissue transglutaminase (tTG), to deamidated gliadin peptide (DGP), to endomysium (EMA) and IgA and IgG antibodies to reticulin (ARA) were assessed, GFR was calculated using the CKD-EPI formula, the ‘office’ blood pressure was measured. Patients with positive CA underwent fibrogastroduodenoscopy (FGDS) with biopsy of the retro-bulbar of the duodenum. The results of the celiac marker study were compared in two groups of patients with IgAN. Group I (n = 10) were patients with IgAN and positive CA; Group II (n = 40) were patients with IgAN and negative CA. Statistical analysis of the data was performed using the SPSS 26.0. The null statistical hypothesis of no difference and no relationship was refuted at P < .05. RESULTS Positive serological markers were found in 20% of the total group of patients with IgAN. IgA antibodies to DGP were positive in 100% of cases; one patient had a one-step increase in IgA antibodies to DGP and IgA antibodies to tTG. No increase of antibodies to ARA and EMA was observed in any case. All Group I patients underwent FGDS; changes in the architectonics of the duodenum were not found. Four patients underwent biopsy of the retro-bulbar of the duodenum according to the Marsh histological classification; all biopsies were classified as Marsh 0–1. The mean concentration of protein in the urine of group I patients was 1.36 (0.76–1.58) g/L and statistically significantly higher than in group II patients 0.6 (0.4–0.93) g/L. (Р = .033). The mean daily proteinuria in celiac antibody-positive patients was 2.38 (0.78–2.8) g/day and was statistically significantly higher than in group II patients at 0.7 (0.6–1.36) g/day (Р = 0.049). We compared the incidence of arterial hypertension (AH) depending on the presence of CA in patients with IgAN. Consistent with the findings, the incidence of AH was statistically significantly higher in group I compared to group II (P = .031). The odds of AH in patients with CA were 9 times higher than in patients with negative CA [95% confidence interval (CI) 1.041–77.803]. The mean diastolic blood pressure was statistically significantly higher in group I—105.1 (96–115) mm Hg. compared to group II—92 (86–98) mm Hg (P = .032). We compared the incidence of chronic tonsillitis (CT) according to the presence of CA in patients with IgAN. According to the data, the incidence of CT was statistically significantly higher in group I compared to group II (Р = .023). The likelihood of having CT was 8.2 times higher in patients with positive antibodies than in those with negative CA (95% CI 1.461–46.272). CONCLUSION Although the patients with IgAN and positive CA did not have gastrointestinal symptoms, and FGDS with a biopsy of the retro-bulbar of the duodenum did not provide convincing evidence for a violation of the intestinal architectonics, we found statistically significant deviations in clinical and laboratory in this group of patients. Our preliminary findings suggest that an isolated increase in CA to exacerbate the course of IgAN. Whether the screening detection of CA, without disrupting intestinal architectonics, can be an additional diagnostic and prognostic marker for patients with IgAN remains a matter of debate to date. In the meantime, further research on this issue is needed, both at clinical and experimental level.

Biochemical abnormalities among patients referred for celiac disease antibody blood testing in a primary health care setting

To investigate possible biochemical abnormalities associated with celiac disease (CD) antibody positivity in a primary health care setting and thereby identify predictors that could potentially reduce diagnostic delay and underdiagnosis of CD. This observational cohort study included measurements of CD antibodies in the Copenhagen Primary Care Laboratory (CopLab) database from 2000 to 2015; CD antibody positivity was defined as tissue transglutaminase antibody IgA or IgG ≥ 7 kU/L and/or deamidated gliadin peptide antibody IgG ≥ 10 kU/L. Individuals with a prior diagnosis of CD were excluded. We examined differences between individuals with positive and negative CD antibody tests regarding the results of biochemical tests performed six months before and one month after the date of the CD antibody test. We identified 76,265 measurements of CD antibodies during 2000–2015, and 57,061 individuals met the inclusion criteria (706 antibody-positive and 56,355 antibody-negative). We found lower ferritin, hemoglobin, cobalamin and folic acid levels and higher levels of transferrin, ALAT (alanine transaminase), and alkaline phosphate among individuals with a positive CD antibody test. Furthermore, we illustrated more measurements below the sex-specific reference intervals for hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), ferritin, cobalamin and folic acid among individuals with a positive CD antibody test. This study identified several biochemical abnormalities associated with CD antibody positivity among individuals referred to CD antibody testing. The pattern of abnormalities suggested that micronutrient deficiencies were prevalent among CD antibody-positive individuals, confirming malabsorption as a sign of CD. These findings illustrate the possibility of reducing diagnostic delay and underdiagnosis of CD.

Usefulness of deamidated gliadin peptide antibodies in diagnosing coeliac disease in children younger than 3 years old.

The standard serological test to screen for coeliac disease (CD) is tissue transglutaminase (tTG) but some experts recommend including deamidated gliadin peptide (DGP) antibodies for children younger than 3 years old. This study evaluated the utility of DGP-immunoglobulin A (IgA) and DGP-immunoglobulin G (IgG) serologies when screening children younger than 3 years old for CD. A retrospective chart review was conducted including children 3 years old and under, who had DGP and/or tTG serologies along with duodenal biopsies during their initial diagnostic evaluation. Serology results were compared to the gold-standard histopathology by χ2 to determine the significance of including DGP-IgG/IgA serologies when screening for CD in this age group. We identified 478 patients, 52 who were younger than 3 years old, 43 of whom met inclusion criteria. The positive predictive value (PPV) of the DGP-IgA test was 91.7% whereas, DGP-IgG was 77.8%. When DGP serology was examined in conjunction with tTG-IgA, the PPV with DGP-IgA was 90.9% and with DGP-IgG was 87.5%. In isolation, DGP-IgA provides a high PPV and specificity for CD in children younger than 3 years old, whereas DGP-IgG had a much lower PPV in this age group. When used alone or in conjunction with tTG-IgA, the DGP-IgA test results in a high PPV of 91.7 and 90.9%, respectively. Based on our study, we recommend obtaining both the DGP-IgA and the tTG-IgA serology when screening infants and children younger than 3 years old for coeliac disease.

Deamidated Gliadin Antibodies: Do They Add to Tissue Transglutaminase-IgA Assay in Screening for Celiac Disease?

Use of deamidated gliadin peptide (DGP) test kits as adjunctive to tissue-transglutaminase-IgA (TTG-IgA) for the diagnosis of celiac disease (CD) has been a controversial issue. The objectives of our study were to evaluate the diagnostic performance of DGP antibodies compared with TTG-IgA and to evaluate the correlation between DGP-antibody titers and degree of enteropathy. We included children who underwent endoscopy and biopsies because of positivity of any of the serology tests in the "celiac profile" (TTG-IgA, DGP-IgA, and DGP-IgG) from 2012 to 2019. We divided children into clinically suspected cases of CD (group 1) and asymptomatic cases screened as they were from a high-risk group (group 2). Group 1 constituted 52 children and group 2 included 81 children (76 type-1 diabetes [T1D]). The sensitivity and positive-predictive value (PPV) of DGP-IgG in group 1 (90%, 98%) and group 2 (91%, 85.5%) were comparable with TTG-IgA (98%, 92% in group 1; 100%, 80% in group 2). By adding DGP-IgG to TTG-IgA, the performance of TTG-IgA has improved marginally in group 1 (sensitivity 100%, PPV 92.3%). All cases with DGP-IgG titer 2 times ULN in group 1, and >4 times ULN in group 2 had villous atrophy. All T1D patients with TTG IgA >10 times ULN had villous atrophy. DGP-IgG assay did not add to the performance of TTG-IgA. DGP-IgG titer correlated with enteropathy. The diagnosis of CD can be made in asymptomatic T1D child with TTG-IgA titer >10 times ULN and positive endomyseal antibodies.

Atherosclerotic Risk Factors in Children with Celiac Disease.

Results We found significantly lower concentrations of total cholesterol, lipoprotein LDL-C, apolipoproteins A1 and B, as well as hCRP in all children with CD. We showed decreased level (<5 ng/mL) of folic acid among 46% of children treated for >5 years. Moreover, we showed significant decrease of folic acid level already after 1 year of a GFD (12 vs. 5.6 ng/mL; p < 0.001). We also found significant negative correlation of z-score body mass index (BMI) with HDL and APOA1 level (r = −0.33; p = 0.015 and r = −0.28; p = 0.038, respectively) and modest positive correlation of z-score BMI with atherogenic factor of total cholesterol-HDL ratio and LDL-HDL ratio (r = 0.40; p = 0.002 and r = 0.36; p = 0.006, respectively). Analysis of physical activity showed an increase in the insulin levels with inactivity (r = 0.36; p = 0.0025). We also found positive correlation of the sleep duration with the adiponectin level (r = 0.41; p = 0.011). Conclusions In children with CD treated with a GFD, decreased level of folic acid together with increased BMI, sedentary behavior, and an improper lipid profile may predispose them to atherosclerosis in the long run. This data suggests the need of further studies to determine the need for metabolic cardiovascular risk screening in children with CD.

European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020.

The ESPGHAN 2012 coeliac disease (CD) diagnostic guidelines aimed to guide physicians in accurately diagnosing CD and permit omission of duodenal biopsies in selected cases. Here, an updated and expanded evidence-based guideline is presented. Literature databases and other sources of information were searched for studies that could inform on 10 formulated questions on symptoms, serology, HLA genetics, and histopathology. Eligible articles were assessed using QUADAS2. GRADE provided a basis for statements and recommendations. Various symptoms are suggested for case finding, with limited contribution to diagnostic accuracy. If CD is suspected, measurement of total serum IgA and IgA-antibodies against transglutaminase 2 (TGA-IgA) is superior to other combinations. We recommend against deamidated gliadin peptide antibodies (DGP-IgG/IgA) for initial testing. Only if total IgA is low/undetectable, an IgG-based test is indicated. Patients with positive results should be referred to a paediatric gastroenterologist/specialist. If TGA-IgA is ≥10 times the upper limit of normal (10× ULN) and the family agrees, the no-biopsy diagnosis may be applied, provided endomysial antibodies (EMA-IgA) will test positive in a second blood sample. HLA DQ2-/DQ8 determination and symptoms are not obligatory criteria. In children with positive TGA-IgA <10× ULN at least 4 biopsies from the distal duodenum and at least 1 from the bulb should be taken. Discordant results between TGA-IgA and histopathology may require re-evaluation of biopsies. Patients with no/mild histological changes (Marsh 0/I) but confirmed autoimmunity (TGA-IgA/EMA-IgA+) should be followed closely. CD diagnosis can be accurately established with or without duodenal biopsies if given recommendations are followed.

Deamidated Gliadin Peptide Antibodies in Celiac Disease: A Diagnostic Driver or just along for the Ride?

Anti deamidated gliadin peptides antibodies are considered as celiac disease associated diagnostic antibodies. They are in clinical use for almost the last two decades. In the first decade they were preferentially used in early childhood, in face of IgA deficiency and occasionally recommended as the prime serological marker, outperforming the anti-tissue transglutaminase autoantibody. Notably, they were recommended in combination with the tissue transglutaminase as enhancer of the diagnostic performances. No more, the circle turned over. In the second decade (2012-2019), most of the studies limited and criticized their past published advantages. They suggested that deamidated gliadin peptides antibodies do not have any advantage over anti-tissue transglutaminase autoantibodies in terms of early childhood, IgA deficiency, diagnostic performances and when both antibodies are combined. It seems that the deamidated gliadin peptide are losing their place in the celiac disease algorithmic diagnostic flow chart.

Prospective longitudinal study: use of faecal gluten immunogenic peptides to monitor children diagnosed with coeliac disease during transition to a gluten-free diet.

SummaryBackgroundTreatment for coeliac disease is a lifelong strict gluten‐free diet. Although guidelines recommend regular follow‐up with dietary interviews and coeliac serology, these methods may be inaccurate.AimTo evaluate the usefulness of faecal gluten immunogenic peptides to support the diagnosis and to determine the adherence to the gluten‐free diet in coeliac children.MethodsMulticentre prospective observational study including 64 coeliac children. Faecal gluten peptides, and tissue transglutaminase and deamidated gliadin peptide antibodies were analyzed at diagnosis, and 6, 12 and 24 months thereafter. Gluten consumption was estimated from gluten peptide levels.ResultsMost children (97%) had detectable gluten peptides at diagnosis. On a gluten‐free diet, the rate of gluten peptides increased from 13% at 6 months to 25% at 24 months. Mean estimated gluten exposure dropped from 5543 mg/d at diagnosis to 144 mg/d at 6 months, then increased to 606 mg/d by 24 months. In contrast, deamidated gliadin peptide antibodies normalised and only 20% had elevated tissue transglutaminase antibody by 24 months. The elevation of tissue transglutaminase antibody was more prolonged in patients with detectable gluten peptides (P < 0.05). Nevertheless, absolute levels of tissue transglutaminase antibody had low sensitivity to identify patients with detectable gluten peptides (P > 0.1). Dietitian assessment was only moderately correlated with gluten peptide detection (κ = 0.5).ConclusionsFaecal gluten peptides testing may guide treatment of coeliac disease prior to diagnosis and during the assessment diet adherence. Further studies could determine if early identification of gluten exposure reduces the need for expensive/invasive investigations for non‐responsive coeliac disease. ClinicalTrials.gov Number: NCT02711397.

Mo1298 – Diagnostic Yield of Isolated Deamidated Gliadin Peptide Antibody for Coeliac Disease in Paediatric Age Group

Mo1298 – Diagnostic Yield of Isolated Deamidated Gliadin Peptide Antibody for Coeliac Disease in Paediatric Age Group

Case-finding in primary care for coeliac disease: Accuracy and cost-effectiveness of a rapid point-of-care test.

BackgroundAn on-site, rapid, fingertip, whole-blood point-of-care test (POCT) is attractive for active case-finding of coeliac disease (CD) in primary care because of its simplicity.AimThe aim of this article is to assess the usefulness and cost-effectiveness of adult case-finding using a POCT based on deamidated gliadin peptide antibodies (IgA/IgG-DGP) in primary care for CD diagnosis.MethodsA case-finding study for CD was conducted by using an easy-to-use, on-site, whole-blood for IgA/IgG-DGP-based fingertip POCT compared with tTG2 in 350 individuals. Sample size was calculated based on 0.28% prevalence in the reference population. Duodenal biopsies for histology, intraepithelial lymphocytes and in situ deposition of tTG2 were obtained if tTG2 and/or POCT were positive. Accuracy and cost-effectiveness of strategies using serology or POCT were calculated.ResultsPrevalence of CD was 1.14% (95% CI, 0.3–3.4), almost double what was previously observed. Four patients were diagnosed with CD. tTG2 was positive in three (0.85%) and POCT in 29 (8.2%). Sensitivity of POCT for CD was 100%, specificity 93%, PPV 14%, and NPV 100%. POCT followed by duodenal biopsy was the most cost-effective approach in our setting (standard diagnosis: €13,033/case; POCT + duodenal biopsy: €7360/case).ConclusionsA negative POCT allows ruling out CD in primary care, making it suitable for case-finding. POCT strategy was the most cost effective.

An Overview of Celiac Disease in Childhood Type 1 Diabetes.

ContextCeliac disease (CD) is a common phenomenon in children with Type 1 diabetes (T1D). In the present review, we have discussed the pathogenesis, diagnostic biomarkers, risk factors, and prognosis of CD in the context of pediatric T1D.Evidence AcquisitionLiterature published in Web of Science, PubMed, Scopus, Google Scholar, and Cochrane Library were scrutinized up to the end of 2017. The keywords of celiac disease, Type 1 diabetes, children, and pediatric were used in different combinations.ResultsImmune cytotoxic reactions along with dampen immune regulatory functions contribute to CD in the context of pediatric T1D. Many children with simultaneous CD and T1D do not represent with the clinical signs of the enteropathy rendering a diagnostic challenge. The most common screening tests in these children are routine serological tests of CD, anti - endomysial, anti - transglutaminase, and anti - deamidated gliadin peptide antibodies. Typing for human leukocyte antigens of DQ - 2 and DQ - 8 may assist in the diagnosis of silent CD in children with T1D. The most significant shared non - HLA genetic loci of CD and T1D comprise CTLA - 4, TAGAP, IL - 18RAP, PTPN2, RGS1, SH2B3, CCR5. Interactions between these loci can be important in susceptibility to CD in T1D. Some new biomarkers have been suggested for diagnosis of CD including ischemia-modified albumin (IMA), soluble syndecan-1 (SSDC-1), regenerating gene Iα (REG-Iα), Neurotensin, and Zonulin, which can be useful for diagnosis and screening of CD in childhood T1D.ConclusionsOverall, active seropositive CD seems to be of clinical importance in T1D with significant impacts on the quality of life and predisposition to diabetes associated complications. It is important to detect CD in the context of T1D to prevent potential risks contributing to morbidities and mortalities associated with either CD or T1D.

Deamidated Gliadin Peptide Antibodies; is the Time to Use as a Routine Test for Celiac Disease

Antibodies to deamidated gliadin peptides (DGP-AGA) have newly been presented into the extensive variety of serologic examinations for celiac disease (CD). In compare with the modern AGA, DGP-AGA indicated a higher sensitivity and specificity for CD and simply identified by ELISA kits. Nevertheless, even though the very favorable outcomes, DGP-AGA are not yet regularly used in the serologic checkup for CD. An antibody approach could initiate development in the diagnostic precision of serology for CD screening.

Clinical and biological correlations in celiac disease in children: the prospective single experience of a romanian tertiary center: A case-control study (Strobe-Compliant study).

Celiac disease—a chronic inflammatory disease of the intestine—is triggered by gluten or associated protein consumption.The aim of our study was to assess the sensitivity, specificity of the combined anti-transglutaminase 2 (TG2)/deamidated gliadin peptide antibodies (DGP), and antiendomisium antibodies (EMA), to determine the distribution of HLA-DQ2/DQ8 for the 140 tested patients, and also to evaluate the clinical and laboratory characteristics of patients admitted with the suspicion of celiac disease (CD). Children included in the study were divided into: group 1, patients with confirmed CD; group 2, patients with “potential" CD; group 3, control group, patients without CD. We assessed the standard laboratory data, the level of TG2/DGP and EMA antibodies, as well as the distribution of HLA molecules in the selected patients. Histopathological examination was considered the criterion standard for diagnosis in most cases.The sensitivity of TG2/DGP was 85% and the specificity 92%. EMA showed a sensitivity of 82% and a specificity of 98%. The vast majority of patients diagnosed with CD were either HLA-DQ2.5 (encoded by DQA1∗05 & DQB1∗02) positive (87.5%) or HLA-DQ8 (encoded by DQB1∗03:02) positive (12.5%). One patient showed a positivity only for HLA-DQ2.2 (encoded by DQA1∗02 & B1∗02).Our study showed that the genetic risk for CD was present in more than one-third of the cases without a confirmed diagnosis of CD. Therefore, the awareness of genetic susceptibility for CD is essential because of the fact that these individuals can develop the disease at any point of their lives. The sensitivity of TG2/DGP and EMA were very similar, whereas EMA presented a higher specificity as that of TG2/DGP.

Diagnostic Yield of Isolated Deamidated Gliadin Peptide Antibody Elevation for Celiac Disease.

Serologic testing for celiac disease includes tissue transglutaminase and endomysial antibodies. In addition to these tools, assays for deamidated gliadin peptide antibodies have been shown to have sensitivity and specificity that are comparable to tissue transglutaminase testing, and are increasingly being used for celiac disease testing. The goal of this study is to evaluate the utility of deamidated gliadin peptide (DGP) testing in the setting of a negative tissue transglutaminase (TTG) IgA test. We reviewed the records of all patients seen at two U.S. celiac disease referral centers and identified those who had an elevated DGP IgA and/or IgG in the setting of a negative TTG IgA. Of these patients, those who underwent duodenal biopsy while on a gluten-containing diet were included. Patients with prior biopsy-proven celiac disease or prior TTG IgA positivity were excluded. The results of the biopsy were used as the gold standard for celiac disease diagnosis, and patients with villous atrophy (Marsh class 3) on duodenal biopsy were considered to have celiac disease. Between the two institutions, 84 patients were identified with negative TTG IgA and positive DGP IgA or IgG who also had duodenal biopsies performed while maintaining a gluten-containing diet. Of these patients, 13 patients (15.5%; 95% CI 8.5-25.0%) were found to have celiac disease on duodenal biopsy. DGP antibody testing can identify cases of celiac disease in TTG-negative individuals, although the low positive predictive value suggests that the yield may be low.

Identification of Pediatric Patients With Celiac Disease Based on Serology and a Classification and Regression Tree Analysis.

Celiac disease is detected using serology and endoscopy analyses. We used multiple statistical analyses of a geographically isolated population in the United States to determine whether a single serum screening can identify individuals with celiac disease. We performed a retrospective study of 3555 pediatric patients (18 years old or younger) in the intermountain West region of the United States from January 1, 2008, through September 30, 2013. All patients had undergone serologic analyses for celiac disease, including measurement of antibodies to tissue transglutaminase (TTG) and/or deamidated gliadin peptide (DGP), and had duodenal biopsies collected within the following year. Modified Marsh criteria were used to identify patients with celiac disease. We developed models to identify patients with celiac disease using logistic regression and classification and regression tree (CART) analysis. Single use of a test for serum level of IgA against TTG identified patients with celiac disease with 90% sensitivity, 90% specificity, a 61% positive predictive value (PPV), a 90% negative predictive value, and an area under the receiver operating characteristic curve value of 0.91; these values were higher than those obtained from assays for IgA against DGP or IgG against TTG plus DGP. Not including the test for DGP antibody caused only 0.18% of celiac disease cases to be missed. Level of TTG IgA 7-fold the upper limit of normal (ULN) identified patients with celiac disease with a 96% PPV and 100% specificity. Using CART analysis, we found a level of TTG IgA 3.2-fold the ULN and higher to most accurately identify patients with celiac disease (PPV, 89%). Multivariable CART analysis showed that a level of TTG IgA 2.5-fold the ULN and higher was sufficient to identify celiac disease in patients with type 1 diabetes (PPV, 88%). Serum level of IgA against TTG in patients with versus those without trisomy 21 did not affect diagnosis predictability in CART analysis. In a population-based study, we found that serum level of IgA against TTG can identify patients with celiac disease with PPVs of about 90%. Predictive values increase greatly when levels are markedly above the ULN or when the assay is used in combination with other variables. Measurement of IgG against TTG or DGP does not increase the accuracy of detection of celiac disease based against TTG IgA levels. There is a low risk of false-positive results from serologic analysis in patients with type I diabetes or persistent increases in antibody against TTG on repeat testing.

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.

The Malabsorption Syndrome versus Celiac Disease: A Diagnostic Reappraisal

The most frequent cause of malabsorption syndrome (MAS) in developed countries is the celiac disease (CD). There are two possible approaches for exact diagnostic of this disorder: in case of full blown clinical symptoms the golden standard is duodenal biopsy. When it shows classical mucosa lesions (Marsh type 3 mucosa atrophy of various grades), the diagnosis of CD is confirmed. However, if intraepithelial lymphocyte infiltration (IEL) and/or hyperplastic crypts can be seen in the absence of mucosa atrophy (Marsh type 1 and/or 2 lesions) only, it is reasonable to examine the serologic markers. The most frequent enzyme linked immunosorbent assay (ELISA) tests are: detection of tissue transglutaminase 2 antibody (anti-tTGase 2, especially of IgA class) and the deamidated gliadin peptide antibody (anti-DGP) assay. A simpler serological test, useful for screening, is the detection of anti-endomysium antibody (AEmA) by indirect fluorescent antibody (IFA) in monkey intestine or esophagus sections. This is reasonable to combine with the microdot test for anti-gliadin antibody (AGA), especially by using the endomysium/gliadin mosaic kit (Euroimmun). Taken together, at least three serological markers (anti-tTGase 2, anti-DGP and AGA) are highly specific for CD; their detection first (i.e. prior to duodenal biopsy) is recommended in children as well as in adults showing atypical, silent and or latent forms of CD. In both of them, serology represents a reliable non-invasive approach, which allows precise diagnosis with a probability of nearly 90 %. Another advantage of the non-invasive serological technic is that it can be easily repeated when following the outcome of gluten-free diet (GFD). Nevertheless, duodenal biopsy should be performed in any case, if the serology does not correlate with clinical symptoms. In such patients as well as in those revealing positive serology but negative and/or non-specific histology, immunogenetic typing should be performed in order to assess the expression of DQ2 [DQA*0501-DQB*0201] or DQ8 [DQA*0301-DQB1*0302] haplotypes of the human leukocyte antigen (HLA) class II region critical for the development of CD.

Sa1405 Utility of Deamidated Gliadin Peptide Antibody Testing For Celiac Disease

Sa1405 Utility of Deamidated Gliadin Peptide Antibody Testing For Celiac Disease