Markers Of Celiac Disease Research Articles

Intestinal Anti-Endomysium Antibodies Are a Useful Tool for Diagnosing Celiac Disease in Pediatric and Adult Patients.

Intestinal anti-endomysium antibodies are a specific marker of celiac disease. The diagnostic accuracy of this marker seems high in pediatric patients and has not yet been investigated in adults, so the aim of this prospective multicentric study was to evaluate the specificity and sensitivity of this marker in childhood and adulthood. Pediatric and adult patients undergoing intestinal endoscopy for any intestinal condition were enrolled. Serological celiac disease markers and HLA type were evaluated in all patients. Intestinal biopsies were analyzed for standard histology and for intestinal anti-endomysium antibodies with biopsy culture assay. In this study, 291 patients (145 adults and 146 children) were included. In the adult population, 34 were diagnosed with celiac disease, 105 were controls, and, in 6, celiac disease was not confirmed. In the pediatric population, 77 were diagnosed with celiac disease, 57 were controls, and, in 12, celiac disease was not confirmed. High diagnostic sensitivity and specificity of intestinal anti-endomysium antibodies were confirmed in children and additionally proven in adults. To conclude, we can affirm that intestinal anti-endomysium antibodies can be detected with high diagnostic accuracy in both children and adults. The implementation of this marker in the diagnostic work-up would help clinicians to correctly identify celiac disease.

Clinical outcomes of potential coeliac disease: a systematic review and meta-analysis

ObjectivePotential coeliac disease (PCD) is characterised by positive serological and genetic markers of coeliac disease with architecturally preserved duodenal mucosa. The clinical outcomes and rates of progression to overt coeliac...

Diagnostic value of serological markers for celiac disease in children

Diagnostic value of serological markers for celiac disease in children

Celiac disease prevalence in patients with idiopathic inflammatory myopathies, a cross-sectional study.

Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies.

Noninvasive Markers of Inflammation and Protein Loss Augment Diagnosis of Pediatric Celiac Disease.

Circulating tissue transglutaminase immunoglobulin A concentration is a sensitive and specific indicator of celiac disease, but discrepancies between serologic and histologic findings occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as noninvasive means of evaluating disease activity. Participants with positive celiac serologies and controls with negative celiac serologies were prospectively enrolled before upper endoscopy. Blood, stool, and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin, and alpha-1-antitrypsin and plasma lipocalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and tissue transglutaminase immunoglobulin A concentration. Lipocalin-2 was significantly elevated in the stool ( P = 0.006) but not the plasma of participants with positive celiac serologies. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100 mg/dL was specific, but not sensitive for biopsy-proven celiac disease. Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role of local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared with controls, an elevation of greater than 100 mg/dL was 90% specific for biopsy-proven celiac disease.

Evaluation of Immunoglobulin’s, Biochemical and Hematological Parameters in Children with Celiac Disease

Celiac disease (CD) is an autoimmune illness which has affected about 1% of the population and it has appeared due to gluten intolerance in genetically susceptible people. The current study was designed to determine the level of immunoglobulin IgA and IgG in children with celiac disease and to estimate their impact on biochemical and hematological parameters. The current study was conducted on 120 subjects, including 60 blood samples were collected from diagnosed celiac disease children aged less than 12 years along with 60 healthy control subjects of same age range. The results of the present study have shown a statistically significant difference between celiac disease patients and control group. Value of immunoglobulin IgA in CD patients was 205.98 ± 181.48 U/ml as compared to the control group i.e. 4.18 ± 1.77 U/ml which showed a statistically significant difference. The mean value of immunoglobulin IgG in patients was 77.21 ± 71.35 U/ml as compared to the control group i.e. 6.13 ± 1.33 U/ml which showed a statistically significant difference. The mean value of Serum alkaline Phosphatase in patients was 382.58 ± 114.99 U/L as associated to the control group i.e. 265.75 ± 65.2 U/L which showed a statistically significant change. The mean value of serum phosphorus in CD patients was 4.64 ± 1.01 mg/dL as compared to the control group i.e. 3.85 ± 0.55 mg/dL which showed a statistically significant difference. It has been concluded from the above results that in most of the cases of CD the values of serum IgA, serum IgG, serum alkaline phosphate, serum calcium, serum phosphorus and hemoglobin values can prove important clinical diagnostic markers for celiac disease which would ultimately be helpful in the management of this life-threatening disease.

Longitudinal screening of HLA-risk and HLA-nonrisk children for celiac disease to age 15 years: CiPiS study.

Autoantibodies against tissue transglutaminase (tTG) are serological markers of celiac disease. The aim was to study the applicability of human leukocyte antigen(HLA)-genotyping and tTG autoantibodies in the screening of celiac disease in a longitudinal birth cohort followed to age 15 years. Included were 13,860 HLA-DQ-genotyped children at birth and previously invited to a screening at age 3 and 9 years, respectively. HLA-DQB1*02 and/or DQB1*03:02 (HLA-risk) children were compared with non-HLA-DQB1*02 and non-DQB1*03:02 (HLA-nonrisk) children. The present study reinvited 12,948/13,860 (93.4%) children at age 15 years of whom 1056/2374 (44.5%) participated in screening at both age 3 and 9 years. Both immunoglobulin A (IgA) and G (IgG) autoantibodies against tTG were analyzed separately in radiobinding assays. Persistently tTG autoantibody-positive children were examined with intestinal biopsy to confirm the diagnosis of celiac disease. At age 3 years, celiac disease was diagnosed in 56/1635 (3.4%) HLA-risk children compared with 0/1824 HLA-nonrisk children (p < 0.001). By age 9 years, celiac disease was diagnosed in 72/1910 (3.8%) HLA-risk children compared with 0/2167 HLA-nonrisk children (p < 0.001). Screening at age 15 years detected 14/1071 (1.3%) HLA-risk children positive for IgA-tTG and/or IgG-tTG of whom 12/1071 (1.1%) remained persistently positive. Among those, 10/1071 (0.9%, 95% confidence interval: 0.4%-1.7%) HLA-risk children were diagnosed with celiac disease compared with 0/1303 HLA-nonrisk children (p < 0.001) and 5/491 (1.0%) were negative in screenings at both 3 and 9 years of age. Screening for celiac disease needs to be performed at multiple timepoints to detect all cases but can be restricted to children at HLA-risk.

Intestinal mRNA expression analysis of polarity-related genes identified the discriminatory ability of CRB3 as a diagnostic marker for celiac disease.

Celiac disease (CD) is a chronic autoimmune disorder characterized by an abnormal immune response to gluten, a protein found in wheat, barley, and rye. It is well established that the integrity of epithelial tight junctions (TJs) and adherens junctions (AJs) plays a crucial role in the pathogenesis of CD. These junctional complexes contribute to the apical-basal polarity of the intestinal epithelial cells, which is crucial for their proper functioning. Sixty CD subjects, and 50 controls were enrolled in the current study. Mucosal samples were obtained from the distal duodenum, total RNA was extracted and complementary DNA was synthesized. The relative expression levels of the desired genes were evaluated by quantitative real-time polymerase chain reaction based on ΔΔCt method. The gene-gene interaction network was also constructed using GeneMANIA. CRB3 (p = .0005), LKB1 (p < .0001), and SCRIB (p = .0005) had lower expression in CD patients compared to controls, while PRKCZ expression did not differ between groups (p > .05). CRB3 represented a significant diagnostic value for differentiating CD patients from the control group (p = .02). The aim of the current study was to evaluate the changes in the mRNA expression levels of SCRIB, PRKCZ, LKB1, and CRB3 genes in the small intestinal biopsy samples of CD patients in comparison to the healthy control subjects. Our data uncover the importance of polarity-related genes (especially CRB3) in CD pahtomechanism, that may facilitate the planning of the future studies looking for finding innovative diagnostic and therapeutic strategies for CD.

A Systems Biology Approach to the Pathogenesis of Celiac Disease: Identification of Potential Protective and Promoting Mechanisms.

Celiac disease (CeD) is an autoimmune enteropathy triggered by dietary gluten. Almost 90% of CeD patients have HLA-DQ2 or -DQ8 haplotypes. As a high proportion of first-degree relatives (FDRs) of CeD patients have the same haplotype, it is assumed that they are at a higher risk of disease development than the general population. Nevertheless, the prevalence of CeD among FDRs is considerably low (7.5%). In order to figure out this discrepancy, a microarray dataset of intestinal mucosal biopsies of CeD patients, FDRs, and control groups was reanalyzed, and a protein-protein interaction network was constructed. Principal component analysis showed that CeD and FDR groups are far away in terms of gene expression. Comparing differentially expressed genes of both networks demonstrated inverse expression of some genes mainly related to cell cycle mechanisms. Moreover, analysis of the modular structures of up- and downregulated gene networks determined activation of protein degradation mechanisms and inhibition of ribosome-related protein synthesis in celiac patients with an upside-down pattern in FDRs. The top-down systems biology approach determined some regulatory pathways with inverse function in CeD and FDR groups. These genes and molecular mechanisms could be a matter of investigation as potential druggable targets or prognostic markers in CeD.

Осведомленность врачей в Узбекистане о целиакии: исследование на основе анкетирования

Objective. To assess the level of awareness of celiac disease, its timely diagnosis and effective treatment among primary care and hospital physicians. Patients and methods. A total of 207 physicians from the Republic of Uzbekistan participated in the study. The questionnaire included 17 questions about clinical manifestations, diagnosis, identification of risk groups and treatment of celiac disease. Results. Only 31.9% of respondents were aware of the autoimmune mechanism of celiac disease. More than 71% of physicians, especially primary care, know well about the typical manifestations of celiac disease (diarrhea, underweight), but quite rarely consider constipation (25.1%), abdominal pain of unknown etiology (46.9%), common colds (24.6%) as a manifestation of celiac disease. Low awareness of the association of celiac disease with autoimmune thyroiditis (20.8%), type 1 diabetes (14.9%), and infertility (34.3%) was shown. Only 43.9% of physicians use to anti-tissue transglutaminase antibodies as serological markers of celiac disease, 30.9% continue to focus on anti-gliadin antibodies. Only 32.9% of patients with suspected celiac disease are referred to a gastroenterologist for evaluation. Conclusion. The results of the study demonstrate a rather low level of awareness of clinical manifestations, methods of diagnosis and treatment of celiac disease among physicians in the Republic of Uzbekistan. It is necessary to develop additional educational programs and introduce modern research methods, especially in remote regions of the country, for timely diagnosis and treatment of celiac disease. Key words: celiac disease, diagnosis, treatment, physicians, survey

Antibody detection by agglutination-PCR (ADAP) assays for the analysis of tissue transglutaminase autoantibodies in celiac disease

Background & aimsTissue transglutaminase autoantibodies (tTGA) are used as diagnostic markers of celiac disease. Different methods have been developed for the detection of tTGA of which enzyme-linked immunosorbent assays (ELISA), radiobinding assays (RBA) and electrochemiluminescence (ECL) assays are the most commonly used. Here we aimed to evaluate a novel antibody detection by agglutination-PCR (ADAP) assay for the detection of tTGA. MethodsIncluded were 126 children with untreated celiac disease (UCD), 64 disease controls (DC), 21 children with potential celiac disease (PCD), and 1501 children from the general population. Tissue TGA were determined using an automated ADAP assay platform and compared with two RBAs for the detection of IgA-tTG and IgG-tTG, respectively. ResultsADAP detected tTGA in 123/126 (97.6%) UCD children compared with 122/126 (96.8%) using RBA-IgA-tTG and RBA-IgG-tTG (p > 0.9999), respectively. Among DC, ADAP detected 5/64 (7.8%) children with tTGA compared with 4/64 (6.3%) with RBA-IgA-tTG (p > 0.9999) and 8/64 (12.5%) with RBA-IgG-tTG (p = 0.5600), respectively. Tissue TGAs were equally detected in children with PCD in both assays. In the general population, 4/1501 (0.3%) were tTGA positive using ADAP compared with 3/1501 (0.2%) for RBA-IgA-tTG and RBA-IgG-tTG (p > 0.9999), respectively. The area under the curves (AUCs) were 0.998 for ADAP, 0.994 for RBA-IgA-tTG, and 0.999 for RBA-IgG-tTG, respectively. ConclusionsNo difference in specificity and sensitivity of tTGA for the diagnosis of celiac disease was reported between ADAP and RBA. ADAP could be recommended as the first-line screening method of larger populations for celiac disease.

Nomenclature and diagnosis of seronegative celiac disease and chronic non-celiac enteropathies in adults

Small bowel villous atrophy is one of the main histopathological manifestations of chronic enteropathy. In most cases, this condition is caused by celiac disease. Celiac disease is an autoimmune disease that occurs in genetically predisposed individuals and is characterized by damage to the mucous membrane of the small intestine (T-cell-mediated enteropathy) due to the influence of gluten and is treated with the help of a lifelong gluten-free diet. Diagnosis of classic celiac disease does not cause difficulties. Diagnostic algorithms have been developed for years. Diagnostic problems arise when small bowel villous atrophy occurs in patients who have gastrointestinal symptoms but are negative for celiac disease-specific antibodies. Differential diagnosis of small bowel villous atrophy without serological markers for celiac disease in adults includes seronegative celiac disease and chronic non-celiac enteropathies. There has long been diagnostic and clinical uncertainty about these conditions. This uncertainty has led to misdiagnoses and increased the number of people following a gluten-free diet unnecessarily. Between September 2019 and July 2021, an international working group of 13 gastroenterologists from six countries worked to create a consensus on the nomenclature and diagnosis of seronegative celiac disease and non-celiac enteropathies in adults.

Overlap syndrome of primary biliary cholangitis and primary sclerosing cholangitis: two case reports

BackgroundOverlap syndrome between primary biliary cholangitis and primary sclerosing cholangitis is an extremely rare condition that has been reported in only few published cases so far in the literature. We highlight here the rarity of this condition and indicate the importance of its recognition.Case presentationWe report two cases showing the manifestations of both primary biliary cholangitis and primary sclerosing cholangitis in two Tunisian female patients aged 74 and 42 years, respectively. The first case is a woman who was initially diagnosed with decompensated cirrhosis. Magnetic resonance cholangiopancreatography showed multiple strictures of the common bile duct, and histological findings led to the diagnosis of primary biliary cholangitis/primary sclerosing cholangitis. She was successfully treated with ursodeoxycholic acid. The second case is a middle-aged woman, suffering from primary biliary cholangitis and who was treated with ursodeoxycholic acid. At her 12 month follow-up appointment, she presented with a partial clinical and biochemical response. Tests showed normal thyroid function, liver autoimmune tests for autoimmune hepatitis were negative, and celiac disease markers were also negative. The diagnosis of overlap syndrome of primary biliary cholangitis/primary sclerosing cholangitis was finally made on the results of magnetic resonance cholangiopancreatography that showed multiple strictures of the common as well as intrahepatic bile ducts. The patient was put on ursodeoxycholic acid at a higher dose.ConclusionsOur cases raise awareness for this rare condition and indicate the importance of recognizing a possible overlap syndrome, especially in patients with primary biliary cholangitis, to optimize treatment. We suggest considering the overlap syndrome of primary biliary cholangitis/primary sclerosing cholangitis when a patient presents with the diagnostic criteria of both diseases.

Celiac disease seroprevalence in patients with infertility. A case-control study.

Although most patients with celiac disease (CD) have digestive manifestations, in some of them they may be of extraintestinal (atypical) nature, such as chronic anemia, ataxia, and fertility disorders. To determine the prevalence of CD-related antibodies in Mexican women with fertility disorders. Case-control study of women who attended evaluation for fertility disorders in a specialized center. h-tTG-IgA, gliadin IgA II and gliadin IgG II were quantified; titers > 30 IU were considered positive. One-hundred and seventy-one cases and 171 controls were included; 137 patients (80.1%) had infertility, and 34 (19.9%), sterility. Eight patients (4.6%, 95% CI = 2.3-8.9) had at least one positive marker for CD in comparison with one woman in the control group (0.5%, 95% CI = 0.01-3, p = 0.04, odds ratio = 8.3). Six of the eight patients had unexplained infertility. Up to 4.6% of women with infertility had at least one positive marker for CD. As in other parts of the world, screening for CD could be recommended in women with infertility, especially in those with unexplained infertility.

The effects of probiotics on gastrointestinal symptoms and microbiota in patients with celiac disease: a systematic review and meta-analysis on clinical trials.

Gluten-free diet (GFD) is the most effective method to manage celiac disease (CD). Many patients do not reach the complete symptom alleviation, even by strict GFD. Recent studies have reported inconsistent results regarding the beneficial benefits of taking probiotics. Therefore, we aimed to evaluate the effects of probiotics on gastrointestinal (GI) symptoms and the possible underlying causes in CD and celiac disease autoimmunity (CDA) patients. Databases, including PubMed, Scopus, Embase, Web of Science and Google Scholar, were searched for clinical trials published until July 2022 about assessing the effects of probiotics or synbiotics on CD or CDA patients. We collected data on GI symptoms, CD markers, inflammatory and immune responses, adverse events, and gut microbiota. A random effect meta-analysis was used to estimate the pooled standardized mean difference (SMD) and confidence interval (CI). We screened 7234 articles, of which 14 were included in the qualitative analysis and 5 in the quantitative analysis. Probiotics might alleviate GI symptoms, especially in the highly symptomatic patients, and improve immune response in CD and CDA patients. Results of the meta-analysis showed that probiotics increased the abundance of Bifidobacterium (SMD: 0.72, 95%CI (0.13, 1.30) and Lactobacillus (SMD: 0.49, 95%CI (0.18, 0.80) as compared with placebo. Probiotics did not increase the adverse events compared to the placebo. Probiotics might alleviate GI symptoms and immune response and improve dysbiosis in CD and CDA patients. However, high-quality clinical trials are needed to increase the level of evidence. Also, the most suitable combination of probiotics is yet to find.

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.

Role of endoscopy in the diagnosis of coeliac disease: a narrative review.

Coeliac disease (CD) is a common autoimmune disorder triggered by gluten consumption in genetically predisposed individuals. CD is characterised by chronic inflammation in the small bowel mucosa with an influx of lymphocytes, followed by crypt hyperplasia and villous atrophy. The gold standard test to diagnose CD is endoscopy with duodenal biopsies. However, variations in practice between endoscopists can lead to missed diagnoses. This review aims to discuss the role of endoscopy in the diagnosis of CD, highlighting the performance measures of endoscopy in CD and the advancement in endoscopic techniques for the optical diagnosis of villous atrophy. We searched PubMed and Google Scholar from their inception to December 2023 for relevant articles on the role of endoscopy in CD. Two authors reviewed these references, and relevant studies were included in the discussion section of this review. We provide an up-to-date assessment of the diagnostic accuracy of endoscopic markers of CD and the performance of enhanced endoscopic imaging to identify villous atrophy during endoscopy. We propose a set of benchmarks for endoscopy in CD and discuss the potential role of artificial intelligence (AI) in the endoscopic diagnosis of CD. Performing high-quality endoscopy and identifying strategies to reduce inter-endoscopist variations may reduce missed diagnoses. Adopting advanced endoscopic techniques and embracing new technologies such as AI could enhance diagnostic accuracy and improve patient care.

Diagnostic performances of celiac disease serological tests among Saudi patients.

: 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. 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). : 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. : 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.

Rapid Immunochromatography on Fresh Intestinal Biopsy Is Highly Accurate in Detecting Intestinal Antitransglutaminase Antibodies.

Intestinal antitransglutaminase antibodies (I-anti-TG2) are a specific marker of celiac disease (CeD). The aim of this study was to evaluate the diagnostic accuracy of a novel application of an immunochromatographic assay referred to as Rapid_AntiTG2 to detect I-anti-TG2 on intestinal biopsy lysate. Consecutive pediatric patients referred to a single center for elective upper endoscopy were enrolled. Biopsies were taken from duodenal bulb and distal duodenum. For each sampling site, 2 biopsies were analyzed for standard histology, 1 biopsy was cultured to perform the reference standard assay for I-anti-TG2 detection (endomysium [EMA] biopsy), and 1 biopsy was mechanically lysed to perform Rapid_AntiTG2. The primary outcome was the diagnostic accuracy of Rapid_AntiTG2 on biopsy lysate compared with that of the gold standard (serology + histopathology) for CeD diagnosis. The secondary outcome was the agreement of Rapid_AntiTG2 with EMA biopsy. One hundred forty-eight patients were included. Of them, 79 were those with CeD (64 classical CeD, 2 seronegative CeD, and 13 potential CeD) and 69 were controls. Rapid_AntiTG2 on biopsy lysate had very high diagnostic accuracy (sensitivity 100%, specificity 97%, LR+ 34.1, LR- 0.01) in separating patients with CeD from controls. Diagnostic accuracy was unchanged in patients with potential and seronegative CeD. Rapid_AntiTG2 on biopsy lysate had almost perfect agreement with the EMA biopsy reference test (99% agreement, Cohen K 0.97). I-anti-TG2 can be detected with an immunochromatographic assay after simple mechanical lysis of fresh intestinal biopsy with very high diagnostic accuracy. The test is quick and easy to perform and can be widely available in any endoscopy unit. Its implementation would allow a better understanding of the prognostic value of I-anti-TG2 and help clinicians in cases of suspected CeD that are difficult to classify.

Focused B cell response to recurring gluten motif with implications for epitope spreading in celiac disease

Antibodies to deamidated gluten peptides are accurate diagnostic markers of celiac disease. However, binding of patient antibodies to all possible gluten epitopes has not previously been investigated. Here, we assess serum antibody specificity across the gluten proteome by use of high-density peptide arrays. We confirm the importance of deamidation for antibody binding, and we show that the response is remarkably focused on the known epitope QPEQPFP (where E results from deamidation of Q). In addition, we describe an epitope in native (non-deamidated) gluten, QQPEQII (where E is gene encoded), which is associated with both B cell and Tcell reactivity. Antibodies to this native epitope are cross-reactive with the major deamidated epitope due to recognition of the shared PEQ motif. Since cross-reactive B cells can present peptides to different gluten-specific Tcells, we propose that such B cells play a role in epitope spreading by engaging Tcells with multiple specificities.