Will the Real Coeliac Disease Please Stand Up? Coeliac Disease Prevalence in the German LIFE Child Study.

Objectives: Assessing the seroprevalence and the prevalence of definite coeliac disease (CD) in the German LIFE Child Health study cohort including immunoglobulin A (IgA) antibodies against tissue transglutaminase (IgA-TTG) in addition to IgG antibodies against deamidated gliadin peptides (IgG-DGP) and human leukocyte antigen (HLA)-DQ2/8 genotyping.

Methods: Samples from children and adolescents were first screened for IgA-TTG and IgG-DGP. If IgA-TTG was above 0.

Antibody Concentrations Decrease 14-Fold in Children With Celiac Disease on a Gluten-Free Diet but Remain High at 3 Months.

Background & Aims: Celiac disease can be identified by a serologic test for IgA against tissue transglutaminase (IgA-TTG) in a large proportion of children. However, the increased concentrations of antibody rarely normalize within the months after children are placed on a gluten-free diet (GFD). Early serologic predictors of sufficient adherence to GFD are required for optimal treatment.

Hemolysis and IgA-antibodies against tissue transglutaminase: When are antibody test results no longer reliable?

Background: Antibodies against tissue transglutaminase (TTG) of isotype IgA (IgA-aTTG) represent reliable diagnostic markers to confirm or exclude celiac disease (CD). Hemolysis (HL) is an important pre-analytical factor. HL can be quantified as HL index (HI) correlating with the concentration of free hemoglobin.

Validation of Antibody-Based Strategies for Diagnosis of Pediatric Celiac Disease Without Biopsy.

Background & Aims: A diagnosis of celiac disease is made based on clinical, genetic, serologic, and duodenal morphology features. Recent pediatric guidelines, based largely on retrospective data, propose omitting biopsy analysis for patients with concentrations of IgA against tissue transglutaminase (IgA-TTG) >10-fold the upper limit of normal (ULN) and if further criteria are met. A retrospective study concluded that measurements of IgA-TTG and total IgA, or IgA-TTG and IgG against deamidated gliadin (IgG-DGL) could identify patients with and without celiac disease.

Primate liver tissue as an alternative substrate for endomysium antibody immunofluorescence testing in diagnostics of paediatric coeliac disease.

Background: Immunofluorescence assays of antibodies against endomysium (EmA) on primate oesophagus sections represent the gold standard in serological testing for coeliac disease (CD). As alternative immunofluorescence technique, staining of primate liver tissue is in use. We compared performance and predictive power of IgA- and IgG-EmA on primate oesophagus and primate liver sections.

Antibodies in the diagnosis of coeliac disease: a biopsy-controlled, international, multicentre study of 376 children with coeliac disease and 695 controls.

Diagnosis of coeliac disease (CD) relies on a combination of clinical, genetic, serological and duodenal morphological findings. The ESPGHAN suggested that biopsy may not be necessary in all cases. New guidelines include omission of biopsy if the concentration of CD-specific antibodies exceeds 10 times the upper limit of normal (10 ULN) and other criteria are met.

Tissue transglutaminase is not a biochemical marker for Alzheimer's disease.

Typical hallmarks of Alzheimer's disease (AD) are pathologic deposits in cortical and subcortical regions consisting of self-aggregated proteins such as amyloid-beta (Aβ) or tau. Tissue transglutaminase (tTG) catalyses calcium-dependent cross-linking between proteins (transamidation) resulting in protease-resistant isopeptide bonds. Because of this ability, tTG was suspected to participate in AD pathogenesis.

Determination of IgG and IgA antibodies against native gliadin is not helpful for the diagnosis of coeliac disease in children up to 2 years old.

Objective: Assays for antibodies against native gliadin (anti-nGli) are still often assumed to perform better in the diagnosis of coeliac disease in young children than tests for antibodies to deamidated gliadin (anti-dGli), tissue transglutaminase (anti-tTG), and endomysium (EmA). We compared the performance of assays for anti-nGli, anti-dGli, anti-tTG, and EmA in this age group.

Methods: We investigated retrospectively 184 children (42 with coeliac disease under normal diet and 142 controls) up to 2 years of age.

Quantification of human tissue transglutaminase by a luminescence sandwich enzyme-linked immunosorbent assay.

Tissue transglutaminase (tTG) is a calcium-dependent enzyme that catalyzes crosslinking of peptidic glutamine residues with primary amines via isopeptide bonds and hydrolysis of ATP or GTP. The enzyme exerts a variety of functions at the cellular and tissue levels that may be disturbed in disease. Its role in pathoprocesses is poorly understood.

Similarity of fine specificity of IgA anti-gliadin antibodies between patients with celiac disease and humanized α1KI mice.

Gliadins, and primarily α-gliadins containing several sequences such as aa 31-49, aa 56-88 (33-mer), aa 57-68, and aa 69-82, are critical in the induction of immune response or toxic reaction leading to the development of celiac disease (CLD). The role of IgA anti-gliadin antibodies (IgA AGA) is unknown. To this end, we prepared several humanized monoclonal IgA AGA using transgenic α1KI mice.

Immunoassay of in vitro activated human tissue transglutaminase.

Tissue transglutaminase (tTG) is a calcium-dependent enzyme that exerts a variety of physiological functions and is involved in various pathoprocesses. To characterize the role of tTG in disease, simple assays are necessary for detection. We developed a highly sensitive enzyme-linked immunosorbent assay (ELISA) that combines a transamidation step with immunological detection to determine tTG.

Use of likelihood ratios improves clinical interpretation of IgG and IgA anti-DGP antibody testing for celiac disease in adults and children.

Objective: To evaluate whether taking into account anti-deamidated gliadin peptide (DGP) antibody concentrations improves clinical interpretation.

Design And Methods: We calculated likelihood ratios (LR) using data from two previously published studies for assays from EUROIMMUN and INOVA.

Results: LRs markedly increased with increasing IgG anti-DGP concentrations.

IgG antibodies against deamidated gliadin peptides for diagnosis of celiac disease in patients with IgA deficiency.

Background: Assays for IgG antibodies against deamidated gliadin (IgG-anti-dGli) are comparable in performance with tests detecting IgA antibodies against tissue transglutaminase (IgA-anti-tTG) in diagnosing celiac disease (CD). IgA-anti-tTG are absent in IgA deficiency, a condition often associated with CD. In IgA deficiency, IgG-anti-tTG, which have a lower overall diagnostic accuracy, are routinely measured.

New developments in serodiagnosis of childhood celiac disease: assay of antibodies against deamidated gliadin.

Antibodies to deamidated gliadin present a new tool in the diagnosis of celiac disease (CD). In children, the ELISA for the determination of IgG antibodies to (deamidated) gliadin-analogous fusion peptides (GAF3X) has a superior performance compared to the ELISA for the determination of antibodies against native gliadin and is comparable to assays for IgA antibodies against tissue transglutaminase (IgA-anti-tTG). The combined investigation of IgG antibodies to GAF3X (IgG-anti-GAF3X) and IgA-anti-tTG significantly increases the fraction of children definitely identified as either CD or non-CD patients.

Endocytotic segregation of gliadin peptide 31-49 in enterocytes.

Objective: Coeliac disease (CD) is a multisystemic autoimmune inflammation of the intestinal tract induced by wheat gluten and related cereals in human leucocyte antigen (HLA)-DQ2/8-positive individuals. The molecular mechanisms relevant to oral tolerance induction towards toxic cereals such as gliadin remain poorly understood. Enterocytes, which express predominantly HLA-DR proteins, are capable of processing, transcytosing and presenting food antigens from the intestinal lumen to T lymphocytes of the lamina propria.

Antibodies against deamidated gliadin as new and accurate biomarkers of childhood coeliac disease.

Objectives: Assays of tissue transglutaminase antibodies (anti-tTG) represent the cornerstone of serological coeliac disease (CD) diagnostics. Assays of antibodies against native gliadin (anti-nGli) lost importance due to low validity. We investigated the performance of new assays for antibodies against deamidated gliadin (anti-dGli) in childhood CD.

Deamidated gliadin peptides as targets for celiac disease-specific antibodies.

Celiac disease (CD) is an (auto)immunologically mediated intestinal intolerance against proteins from wheat (gluten) and related cereal proteins. Tissue transglutaminase (tTG) has been identified as the autoantigen in CD. Although ultimate diagnosis is based on histological analysis of small intestinal mucosa obtained via tissue biopsy, assessment of autoantibodies can provide substantial help in the evaluation of CD.

Specificity analysis of anti-gliadin mouse monoclonal antibodies used for detection of gliadin in food for gluten-free diet.

A gluten-free diet (GFD) is the sole effective long-lasting treatment of celiac disease. Four monoclonal antibodies (Abs) were prepared by immunization of animals kept on GFD with gliadin. The specificity of these Abs to decapeptides of alpha- and gamma-gliadin and omega-secalin was analyzed by the PEPSCAN technique.

Serologic assay based on gliadin-related nonapeptides as a highly sensitive and specific diagnostic aid in celiac disease.

Background: Celiac disease (CD) is induced by wheat gliadins and related cereal proteins. Anti-gliadin antibodies (AGAs) are present in the serum of CD patients, but these antibodies have lower diagnostic specificity and sensitivity than autoantibodies [anti-endomysium antibodies (AEmAs) and anti-tissue transglutaminase antibodies (AtTGAs)]. Recently, AGAs from CD patients were found to recognize deamidated gliadin peptides, probably formed by the action of tissue transglutaminase.

Intrathecal synthesis of autoantibodies against tissue transglutaminase.

Anti-tissue transglutaminase (tTG) antibodies (AtTGA) are typically found in serum of patients with untreated coeliac disease (CD). tTG catalyses crosslinking of peptides an activity supposed to be important in neurological disorders. tTG occurs in cerebrospinal fluid (CSF) and its assay in CSF was suggested to be diagnostically useful.

Epitopes of calreticulin recognised by IgA autoantibodies from patients with hepatic and coeliac disease.

Calreticulin (CRT) was identified as a frequent target of serum autoantibodies (Ab) in various diseases, but anti-CRT Ab of IgA isotype were described only in coeliac (CLD) and some hepatic diseases. Employing ELISA with recombinant CRT we found significantly higher (P<0.001) levels of IgA anti-CRT Ab in sera of patients with primary biliary cirrhosis (PBC) (77.

Assay of gliadin by real-time immunopolymerase chain reaction.

Patients with coeliac disease (gluten-sensitive enteropathy) are intolerant against gliadins from wheat and the respective proteins from related cereals and have to keep a lifelong gluten-free diet. For control of gliadin in gluten-free food sensitive assay techniques are necessary. We developed an immunopolymerase chain reaction (iPCR) assay for gliadin.

How gluten-free is gluten-free, and what does this mean to coeliac patients?

A gluten-free diet is the cornerstone treatment of coeliac disease. Until now, it is not known conclusively whether trace amounts of gluten might be allowed in the diet, as suggested by Codex Alimentarius. Gluten-free foods intended for dietary use can now be analysed reliably for residual gluten by the new R5 enzyme-linked immunosorbent assay (ELISA) system.