Diagnostic Accuracy of IgA Anti-Transglutaminase Assessed by Chemiluminescence: A Systematic Review and Meta-Analysis.

A new chemiluminescence immunoassay method (CLIA) for detecting IgA anti-transglutaminase (atTG IgA) in celiac disease (CD) has prompted inquiries into its diagnostic performance. We conducted a systematic review and meta-analysis comparing CLIA with traditional enzyme-linked immunosorbent assay (ELISA) and fluorescence enzyme immunoassay (FEIA). We searched PubMed, Medline, and Embase databases up to March 2024. The diagnostic references were intestinal biopsy and ESPGHAN guidelines. We calculated the sensitivity and specificity of atTG IgA assessed by CLIA and the odds ratio (OR) between the assays. Eleven articles were eligible for the systematic review and seven for the meta-analysis. Sensitivity and specificity of atTG IgA CLIA-assay were 0.98 (95% CI, 0.95-0.99) and 0.97 (95% CI, 0.94-0.99), respectively. The sensitivity of atTG IgA antibody detection did not significantly vary across the three assay modalities examined (CLIA vs. ELISA OR: 1.08 (95% CI, 0.56-2.11; p = 0.8); CLIA vs. FEIA OR: 6.97 (95% CI, 0.60-81.03; p = 0.1). The specificity of atTG IgA assessed by FEIA was higher than for CLIA (OR 0.17 (95% CI, 0.05-0.62); p < 0.007). According to the systematic review, normalization of atTG IgA levels in CD patients following a gluten-free diet was delayed when using CLIA compared to ELISA and FEIA methods. Conflicting findings were reported on the antibody threshold to use in order to avoid biopsy confirmation.

Autoantibodies related to ataxia and other central nervous system manifestations of gluten enteropathy.

Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies. In this narrative review, we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease, immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following. We focused on the anti-gliadin antibodies, antibodies to different isoforms of tissue transglutaminase (TG) (anti-TG2, 3, and 6 antibodies), anti-glycine receptor antibodies, anti-glutamine acid decarboxylase antibodies, anti-deamidated gliadin peptides antibodies, etc. Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction, presented as different neurological disorders. We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.

The role of serology in the diagnosis of coeliac disease.

Serology has significantly revolutionized the knowledge of celiac disease (CD), leading to the identification of unsuspected patients in at-risk CD groups, thereby increasing the number of CD diagnoses compared to the pre-screening era. Several markers for CD with a progressive diagnostic accuracy have been identified over the years, but only three of them, i.e. anti-tissue transglutaminase (anti-tTG), anti-endomysial (EmA) and anti-deamidated gliadin antibodies (DGP) are currently assessed in the daily clinical practice. A thorough review of the literature identified 44 original studies published between 1998 to 2022 for a total of 5098 pediatric and adult CD patients (without selective IgA deficiency) and 11930 disease controls. The results highlighted that anti-tTG IgA exhibited a higher sensitivity for CD (93.4%) than EmA IgA (92.8%), DGP IgG (81.8%) and DGP IgA (83.8%). The specificity of EmA IgA (99%) resulted to be higher than those of anti-tTG IgA (95.8%), DGP IgG (96.4%) and DGP IgA (92.1%). In patients with selective IgA deficiency, a condition closely related to CD, serological screening should include one of the three antibodies of IgG class, since anti-tTG, DGP and EmA have a very similar diagnostic accuracy in this clinical setting. According to age, there are two main diagnostic strategies for CD detection. In children, the revised ESPGHAN 2020 guidelines established that CD could be diagnosed in both symptomatic and asymptomatic children by high anti-tTG IgA titers (>10 times the cut-off) and EmA positivity with no need to obtain duodenal biopsy and HLA typing. In adult patients, although high tTG IgA titers (confirmed by EmA IgA positivity) correlate with villous atrophy, an intestinal biopsy is still considered mandatory for confirming CD diagnosis. Currently, a case finding approach in at-risk groups is preferred to mass screening for CD detection.

Antibody Profile, Gene Expression and Serum Cytokines in At-Risk Infants before the Onset of Celiac Disease.

Immunological events that precede the development of villous atrophy in celiac disease (CeD) are still not completely understood. We aimed to explore CeD-associated antibody production (anti-native gliadin (AGA), anti-deamidated gliadin (DGP) and anti-tissue transglutaminase (anti-tTG)) in infants at genetic risk for CeD from the Italian cohorts of the PREVENT-CD and Neocel projects, as well as the relationship between antibody production and systemic inflammation. HLA DQ2 and/or DQ8 infants from families with a CeD case were followed from birth. Out of 220 at-risk children, 182 had not developed CeD by 6 years of age (CTRLs), and 38 developed celiac disease (CeD). The profiles of serum cytokines (INFγ, IL1ß, IL2, IL4, IL6, IL10, IL12p70, IL17A and TNFα) and the expression of selected genes (FoxP3, IL10, TGFß, INFγ, IL4 and IL2) were evaluated in 46 children (20 CeD and 26 CTRLs). Among the 182 healthy CTRLs, 28 (15.3%) produced high levels of AGA-IgA (AGA+CTRLs), and none developed anti-tTG-IgA or DGP-IgA, compared to 2/38 (5.3%) CeD infants (Chi Sq. 5.97, p = 0.0014). AGAs appeared earlier in CTRLs than in those who developed CeD (19 vs. 28 months). Additionally, the production of AGAs in CeD overlapped with the production of DGP and anti-tTG. In addition, gene expression as well as serum cytokine levels discriminated children who developed CeD from CTRLs. In conclusion, these findings suggest that the early and isolated production of AGA-IgA antibodies is a CeD-tolerogenic marker and that changes in gene expression and cytokine patterns precede the appearance of anti-tTG antibodies.

Diagnostic performances of celiac disease serological tests among Saudi patients.

Background: : The prevalence of celiac disease (CD) is relatively high in Saudi Arabia, and little is known about the accuracy of serological markers in the local population. This study aimed to assess the diagnostic performance of various serological markers for detecting CD in Saudi children and adults. Methods: We conducted a retrospective study of 148 CD patients and 512 controls to assess the diagnostic performances of IgA anti-tissue transglutaminase antibodies (TTG), IgG anti-TTG, IgA anti-deamidated gliadin peptide antibodies (anti-DGP), IgG anti-DGP, and endomysium antibodies (EMA). Results: : Immunoglobulin A (IgA) anti-TTG was the most sensitive test [98.9% (95% confidence interval (CI) 94.1-99.8%)], while EMA was the most specific [100%, 95%CI 98.6-100%]. By applying the criteria of IgA anti-TTG titers ≥10 × upper limit of normal (ULN) and positive EMA, 57.3% of patients could have avoided intestinal biopsy. IgG anti-DGP test had a sensitivity of 85.9% (95% CI = 77.3-91.5%) and a specificity of 93.5% (95% CI = (90.0-95.9%). Titers of IgA anti-TTG, IgA anti-DGP, and IgG anti-DGP were higher in CD patients with the Marsh 3c class than in those with the Marsh 3b and Marsh 3a classes. IgG anti-TTG and IgA anti-DGP had no additional diagnostic value. Conclusions: : IgA anti-TTG and EMA are excellent CD markers in children and adults. The use of IgA anti-TTG titers ≥10 × ULN and positive EMA as criteria for CD diagnosis in children and adults might be a good alternative to intestinal biopsy.

In a large Juvenile Idiopathic Arthritis (JIA) cohort, concomitant celiac disease is associated with family history of autoimmunity and a more severe JIA course: a retrospective study.

BACKGROUND: A higher prevalence of celiac disease (CD) has been reported in patients with juvenile idiopathic arthritis (JIA) compared to the general population. Factors related to the increased risk of co-occurrence and associated disease course have not been fully elucidated. Aims of this study were to determine the prevalence of CD in a large Southern Italian cohort of children with JIA, describe their clinical features and disease course and investigate risk factors associated with their co-occurrence. FINDINGS: Demographic, clinical and laboratory data of all patients with JIA admitted to our Pediatric Rheumatology Unit from January 2001 to June 2019, who underwent CD screening, were retrospectively extracted from clinical charts and analyzed. Eight of 329 JIA patients were diagnosed with CD, resulting in a prevalence higher than the general Italian population (2.4% vs 0.93%, p < 0.05). Familiarity for autoimmunity was reported by 87.5% patients with JIA and CD compared to 45.8% of those without CD (p < 0.05). 87.5% patients with JIA and CD required both a conventional Disease Modifying Anti-Rheumatic Drug (DMARD) and a biological DMARD over time compared to 36.4% of those without CD (p < 0.05). CONCLUSION: A higher CD prevalence was found in a large JIA cohort, supporting the need for CD screening in all JIA children, especially those with a family history of autoimmunity, found to be associated with the co-occurrence of the two diseases. This is clinically relevant since patients with CD and JIA more often required a step-up therapy, suggesting a more severe JIA clinical course.

Gluten-free diet adherence and implications for the diagnosis of coeliac disease.

Coeliac disease (CD) is an autoimmune disorder caused by the ingestion of gluten containing foods in genetically susceptible individuals, with a worldwide prevalence of up to 1%. Currently, the only available treatment is a gluten-free diet (GFD). Screening for CD is primarily performed using serum based testing for anti-tissue transglutaminase (tTG) antibodies. Patients must be on a gluten containing diet at the time of testing to ensure an accurate serological result. We investigated the prevalence of a GFD in hospital clinic settings and the general population using survey data to estimate the proportion of CD patients that may be misdiagnosed for CD based on serological tests. Data were collected at clinics of a metropolitan hospital in Sydney, Australia, and the general population. Data from Medicare Benefits Scheme and tTG results from a large Australian private laboratory were reviewed for comparison. Of 778 participants who responded to the survey, 58 (7.5%) were on a GFD. More patients attending the immunology (15.9%) and gastroenterology (12.1%) clinics adopted a GFD than those attending the diabetes (2.6%) or endocrinology (6.1%) clinics, or in the general population (4.3%). More females than males excluded gluten from their diet (p<0.0001). Medicare statistics between 2013 and 2019 demonstrated an increase in CD serological testing; however, tTG data from a private pathology highlighted a stable level of elevated tTG antibodies of 3% of total tests performed. The high number of individuals on a GFD is likely impacting the ability to accurately diagnose CD using serum-based testing.

Serological Screening of Celiac Disease in Patients with Juvenile Idiopathic Arthritis.

There is a possible association between celiac disease (CD) and juvenile idiopathic arthritis (JIA). Our aim was to evaluate the serological incidence of CD in patients with JIA. Children under 16 years of age with JIA who did not respond adequately to routine treatment, who referred to the pediatric centers of Tehran University of Medical Sciences (2017-2019), were enrolled in this study. Manifestations of CD were also evaluated. CD-related serological screening tests were measured. Seventy-eight patients were enrolled in the study. Their mean age was 7.9±3.9 (1.6-16) years. Three patients with oligoarticular JIA had Anti-TTG-Ab levels above normal (prevalence=3.8%). None of them had symptoms of CD. There were no significant statistical differences in terms of growth disorders, sex distribution, and different subtypes of JIA (P value ˃ 0.05) between the groups (sero-positive vs. sero-negative). In one case, CD was confirmed by pathology and the gluten-free diet was recommended. The absence of CD symptoms in patients with JIA does not rule out concomitant CD.

Reliability of anti-tissue transglutaminase antibodies in children with malnutrition.

OBJECTIVES: Serological markers are used in the diagnosis of celiac disease. Among these, the most widely used are tissue transglutaminase antibodies (anti-TG2 antibodies). It has been suggested that the mechanisms that are set in motion by malnutrition cause the tight connections between enterocytes to expand, which allows gluten-derived peptides to pass through the epithelium. This causes the production of anti-TG2 antibodies without the presence of celiac disease. METHODS: The patients who were examined for malnutrition and had their anti-TG2 antibody levels measured at the same time, were accepted into the study. The patients who were investigated for suspected celiac disease, showed no signs of malnutrition, and had their anti-TG2 antibody levels measured were accepted into a control group. RESULTS: The study population consisted of 126 children with mild malnutrition (54.8% female, 7.44 ± 5.38 years); 89 children with moderate malnutrition (54.8% female, 7.62 ± 5.43 years), and a control group of 200 children (53.2% female, 7.72 ± 5.05 years). According to the results, anti-TG2 IgG levels were significantly higher among patients in the mild and moderate malnutrition groups compared to patients in the control group (p = .02 and p = .01, respectively). However, there was no significant difference between the mild and moderate malnutrition groups (p > .05). CONCLUSIONS: Malnutrition does not affect anti-TG2 IgA levels in children. However, anti-TG2 IgG levels increase in children suffering from malnutrition. When examining celiac disease, especially in people with a background IgA deficiency, doctors should consider whether malnutrition may be the cause of the increase in serum anti-TG2 IgG levels without celiac disease.

Positive tissue transglutaminase antibodies with negative endomysial antibodies: Unresolved issues in diagnosing celiac disease.

BACKGROUND: The serological screening for celiac disease (CD) is currently based on the detection of anti-transglutaminase (tTG) IgA antibodies, subsequently confirmed by positive endomysial antibodies (EMA). When an anti-tTG IgA positive/EMA IgA negative result occurs, it can be due either to the lower sensitivity of the EMA test or to the lower specificity of the anti-tTG test. This study aimed at verifying how variation in analytical specificity among different anti-tTG methods could account for this discrepancy. METHODS: A total of 130 consecutive anti-tTG IgA positive/EMA negative samples were collected from the local screening routine and tested using five anti-tTG IgA commercial assays: two chemiluminescence methods, one fluoroimmunoenzymatic method, one immunoenzymatic method and one multiplex flow immunoassay method. RESULTS: Twenty three/130 (17.7%) patients were diagnosed with CD. In the other 107 cases a diagnosis of CD was not confirmed. The overall agreement among the five anti-tTG methods ranged from 28.5% to 77.7%. CD condition was more likely linked to the positivity of more than one anti-tTG IgA assay (monopositive = 2.5%, positive with ≥ three methods = 29.5%; p = 0.0004), but it was not related to anti-tTG IgA antibody levels (either positive or borderline; p = 0.5). CONCLUSIONS: Patients with positive anti-tTG/negative EMA have a low probability of being affected by CD. Given the high variability among methods to measure anti-tTG IgA antibodies, anti-tTG-positive/EMA-negative result must be considered with extreme caution. It is advisable that the laboratory report comments on any discordant results, suggesting to consider the data in the proper clinical context and to refer the patient to a CD reference center for prolonged follow up.

Non-invasive prediction of persistent villous atrophy in celiac disease.

BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathy that is primarily treated with a gluten-free diet (GFD). Mucosal healing is the main target of the therapy. Currently, duodenal biopsy is the only way to evaluate mucosal healing, and non-invasive markers are challenging. Persistent elevation of anti-tissue transglutaminase antibodies (aTTG) is not an ideal predictor of persistent villous atrophy (VA). Data regarding prediction of atrophy using anti-deamidated gliadin peptide antibodies (aDGP) and abdominal ultrasonography are lacking. AIM: To evaluate the ability of aTTG, aDGP, small bowel ultrasonography, and clinical and laboratory parameters in predicting persistent VA determined using histology. METHODS: Patients with CD at least 1 year on a GFD and available follow-up duodenal biopsy, levels of aTTG and aDGP, and underwent small bowel ultrasonography were included in this retrospective cohort study. We evaluated the sensitivity, specificity, and positive and negative predictive values of aTTG, aDGP, small bowel ultrasonography, laboratory and clinical parameters to predict persistent VA. A receiver operating characteristic (ROC) curve analysis of antibody levels was used to calculate cut off values with the highest accuracy for atrophy prediction. RESULTS: Complete data were available for 82 patients who were followed up over a period of four years (2014-2018). Among patients included in the analysis, women (67, 81.7%) were predominant and the mean age at diagnosis was 33.8 years. Follow-up biopsy revealed persistent VA in 19 patients (23.2%). The sensitivity and specificity of aTTG using the manufacturer's diagnostic cutoff value to predict atrophy was 50% and 85.7%, respectively, while the sensitivity and specificity of aDGP (using the diagnostic cutoff value) was 77.8% and 75%, respectively. Calculation of an optimal cutoff value using ROC analysis (13.4 U/mL for aTTG IgA and 22.6 U/mL for aDGP IgA) increased the accuracy and reached 72.2% [95% confidence interval (CI): 46.5-90.3] sensitivity and 90% (95%CI: 79.5-96.2) specificity for aDGP IgA and 66.7% (95%CI: 41.0-86.7) sensitivity and 93.7% (95%CI: 84.5-98.2) specificity for aTTG IgA. The sensitivity and specificity of small bowel ultrasonography was 64.7% and 73.5%, respectively. A combination of serology with ultrasound imaging to predict persistent atrophy increased the positive predictive value and specificity to 88.9% and 98% for aTTG IgA and to 90.0% and 97.8% for aDGP IgA. Laboratory and clinical parameters had poor predictive values. CONCLUSION: The sensitivity, specificity, and negative predictive value of aTTG and aDGP for predicting persistent VA improved by calculating the best cutoff values. The combination of serology and experienced bowel ultrasound examination may achieve better accuracy for the detection of atrophy.

Poor Sensitivity of Fecal Gluten Immunogenic Peptides and Serum Antibodies to Detect Duodenal Mucosal Damage in Celiac Disease Monitoring.

A lifelong gluten-free diet (GFD) is the only current treatment for celiac disease (CD), but strict compliance is complicated. Duodenal biopsies are the "gold standard" method for diagnosing CD, but they are not generally recommended for disease monitoring. We evaluated the sensitivity and specificity of fecal gluten immunogenic peptides (GIPs) to detect duodenal lesions in CD patients on a GFD and compared them with serum anti-tissue transglutaminase (tTG) IgA antibodies. A prospective study was conducted at two tertiary centers in Spain on a consecutive series of adolescents and adults with CD who maintained a long-lasting GFD. Adherence to a GFD and health-related quality of life were scored with validated questionnaires. Mucosal damage graded according to the Marsh-Oberhüber classification (Marsh 1/2/3) was used as the reference standard. Of the 97 patients included, 27 presented duodenal mucosal damage and 70 had normal biopsies (Marsh 0). The sensitivity (33%) and specificity (81%) of GIPs were similar to those provided by the two assays used to measure anti-tTG antibodies. Scores in questionnaires showed no association with GIP, but an association between GIPs and patients' self-reported gluten consumption was found (p = 0.003). GIP displayed low sensitivity but acceptable specificity for the detection of mucosal damage in CD.

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 in a large cohort of young patients with type 1 diabetes.

BACKGROUND: Serological screening for celiac disease (CD) allows the identification of individuals genetically predisposed, as type 1 diabetes mellitus (T1DM). However, the diagnosis is confirmed by intestinal biopsy. The aim was to determine the prevalence of immunoglobulin-A anti-tissue transglutaminase antibodies (IgA-tTG) and CD in a large cohort of young T1DM patients. METHODS: Screening for CD was randomly conducted in 881 T1DM by IgA-tTG and total IgA. Individuals with positive antibodies were referred to endoscopy/duodenal biopsy. RESULTS: The age of the cohort at the screening was 14.3 ± 5.9 years and at T1DM onset was 7.9 ± 4.4 years. The prevalence of positive serology was 7.7%. Median IgA-tTG levels were 117.7 U/mL (interquartile range [IQR] 35.7-131.5 U/mL). Of the 62 duodenal biopsy, CD was diagnosed in 79.0%, yielding an overall prevalence of 5.6%. The mean age of CD patients was 15.6 ± 6.5 years and, at T1DM onset was 6.3 years (4.0-9.9 years). The modified Marsh-Oberhuber histological classification was 22.5% (3a), 36.7% (3b), and 40.8% (3c). In the biopsy-proven patients, T1DM onset occurred at slightly younger ages (6.3 vs 9.7 years, P = 0.1947), gastrointestinal (GI) manifestations, predominantly abdominal pain and distension, were more prevalent (71.4% vs 38.5%, P = 0.027) and higher IgA-tTG titers (128.0 vs 26.3 U/mL, P = 0.0003) were found than in those with negative-biopsies. CONCLUSION: Our results demonstrate the prevalence of 7.7% of IgA-tTG and 5.6% of CD in T1DM patients in South Brazil and, emphasize the importance of the screening in high-risk individuals. Furthermore, the presence of GI manifestations and higher IgA-tTG titers strongly suggest the diagnosis of CD.

Disulfide-modified antigen for detection of celiac disease-associated anti-tissue transglutaminase autoantibodies.

A simple and rapid immunosensor for the determination of the celiac disease-related antibody, anti-tissue transglutaminase, was investigated. The antigenic protein tissue transglutaminase was chemically modified, introducing disulfide groups through different moieties of the molecule (amine, carboxylic, and hydroxyl groups), self-assembled on gold surfaces, and used for the detection of IgA and IgG autoantibodies. The modified proteins were evaluated using enzyme-linked immunosorbent assay and surface plasmon resonance, which showed that only introduction of the disulfide groups through amine moieties in the tissue transglutaminase preserved its antigenic properties. The disulfide-modified antigen was co-immobilized via chemisorption with a poly(ethylene glycol) alkanethiol on gold electrodes. The modified electrodes were then exposed to IgA anti-tissue transglutaminase antibodies and subsequently to horseradish peroxidase-labeled anti-idiotypic antibodies, achieving a detection limit of 260 ng ml-1. Immunosensor performance in the presence of complex matrixes, including clinically relevant serum reference solutions and real patient samples, was evaluated. The introduction of disulfides in the antigenic protein enabled a simple and convenient one-step surface immobilization procedure involving only spontaneous gold-thiol covalent binding. Complete amperometric assay time was 30 min.

Celiac Disease in Children with Severe Acute Malnutrition (SAM): A Hospital Based Study.

OBJECTIVES: To evaluate the prevalence and clinical features of Celiac disease among children with severe acute malnutrition (SAM). METHODS: This prospective observational study was conducted in PBM Children Hospital, Bikaner from July 2012 through December 2013. All consecutively admitted children with SAM were recruited. All subjects were screened for Celiac disease by serological test for IgA-anti tissue Transglutaminase (IgA tTG) antibodies. All seropositive children underwent upper gastrointestinal endoscopy for small bowel biopsy for the confirmation. Clinical features of patients with and without celiac disease were compared. RESULTS: The sero-prevalence (IgA tTg positivity) of Celiac disease was found to be 15.38% while prevalence of biopsy confirmed Celiac disease was 14.42% among SAM children. Abdominal distension, diarrhea, anorexia, constipation, pain in abdomen, vitamin deficiencies, edema, clubbing and mouth ulcers were more common in patients of Celiac disease compared to patients without Celiac disease but the difference was statistically significant only for abdominal distension and pain abdomen. CONCLUSIONS: There is a high prevalence of Celiac disease in SAM. Screening for Celiac disease (especially in presence of pain abdomen and abdominal distension) should be an essential part of work-up in all children with SAM.

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.

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.

Assessment of the response to gluten-free diet in an Iraqi population with coeliac disease. A histological and serological follow-up study.

INTRODUCTION: Coeliac disease (CD) is a common diagnosis among children and adults in Iraq; however, removal of gluten from the diet is essential for patients with CD. The aim of this study, the first such study in Iraq, was to assess the serological and histological recovery profiles of coeliac patients, in both children and adults groups after commencing a gluten-free diet (GFD) for at least 1 year ± 1 month. MATERIAL AND METHODS: The study group comprised 78 proved coeliac patients (46 children and 32 adults, median age: 15 years, range: 1-66 years) who all agreed to undergo endoscopy in addition to serological assessment before and after treatment. The duodenal biopsies were interpreted histologically according to modified Marsh criteria and the sera were tested for anti-gliadin antibody (AGA), endomysium antibody (EMA) and anti-tissue transglutaminase antibody (tTG). RESULTS: Complete histological remission was seen in 29 (63.1%) of 46 treated children CD patients, while only 5 (10.9%) showed Marsh IIIa changes compared with 11 (24%) before GFD. Similarly none of the 32 adults after GFD showed Marsh IIIb and Marsh IIIc compared with 46.9% and 28.1% before treatment respectively (p = 001). Meanwhile, there was strongly significant reduction in AGA, EMA, and tTG antibodies levels (p = 0.00001) following GFD. CONCLUSIONS: Repeating the duodenal biopsy 1 year ±1 month after diagnosis and starting a GFD supports the routine measurement of using histological findings as a gold standard test to confirm recovery of Iraqi CD patients along with using known coeliac serology antibodies.

Diagnosis and classification of celiac disease and gluten sensitivity.

Celiac disease is a complex disorder, the development of which is controlled by a combination of genetic (HLA alleles) and environmental (gluten ingestion) factors. New diagnostic guidelines developed by ESPGHAN emphasize the crucial role of serological tests in the diagnostic process of symptomatic subjects, and of the detection of HLA DQ2/DQ8 alleles in defining a diagnosis in asymptomatic subjects belonging to at-risk groups. The serological diagnosis of CD is based on the detection of class IgA anti-tissue transglutaminase (anti-tTG) and anti-endomysial antibodies. In patients with IgA deficiency, anti-tTG or anti-deamidated gliadin peptide antibody assays of the IgG class are used. When anti-tTG antibody levels are very high, antibody specificity is absolute and CD can be diagnosed without performing a duodenum biopsy. Non-celiac gluten sensitivity is a gluten reaction in which both allergic and autoimmune mechanisms have been ruled out. Diagnostic criteria include the presence of symptoms similar to those of celiac or allergic patients; negative allergological tests and absence of anti-tTG and EMA antibodies; normal duodenal histology; evidence of disappearance of the symptoms with a gluten-free diet; relapse of the symptoms when gluten is reintroduced.