New Serology Assays Can Detect Gluten Sensitivity among Enteropathy Patients Seronegative for Anti–Tissue Transglutaminase

Abstract Background: Some patients with celiac disease (CD) may be seronegative with the commonly used test for IgA anti–tissue transglutaminase (anti-tTG) antibodies. Our aim was to explore whether newer assays incorporating synthetic deamidated gliadin-related peptides (DGPs) or other TG isoenzymes as antigen are useful for detecting gluten sensitivity in IgA anti-tTG–seronegative patients. Methods: We assayed serum samples obtained at diagnosis from (a) anti-tTG–seronegative patients with a CD-like enteropathy (n = 12), (b) skin biopsy–proven dermatitis herpetiformis (DH) patients (n = 26), and (c) IgA anti-tTG–positive CD patients (n = 26). All patients had typical total IgA concentrations. All patients underwent intestinal biopsy and serum testing for (a) detection of IgA and IgG isotypes of both anti-DGP and anti-tTG in a single assay (tTG/DGP Screen; INOVA Diagnostics), (b) simultaneous detection of both IgA and IgG anti-DGP antibody isotypes (DGP Dual; INOVA Diagnostics), and (c) detection of antibodies to transglutaminase 3 (TG3) or transglutaminase 6 (TG6). Results: All anti-tTG–seropositive patients also tested positive in anti-DGP assays. Overall, tTG/DGP Screen detected 6 (31.6%) of the 19 anti-tTG seronegatives, and anti-DGP Dual produced positive results in 5 (26.3%) of these cases. Whereas both assays detected 2 anti-tTG–negative DH patients with partial villous atrophy, they were positive in only 2 of the 5 cases with no histologically discernible mucosal damage. Testing for antibodies to TG3 and TG6 identified 7 (36.8%) of the 19 anti-tTG–negative patients, 5 of which were also positive for anti-DGP. Conclusions: Detection of anti-DGP with tTG/DGP Screen or anti-DGP Dual, or detection of antibodies to other TG isoenzymes, enhances the sensitivity for detecting gluten sensitivity among non–IgA- deficient, anti-tTG–seronegative patients with CD-like enteropathy.

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SAT-071 Autoimmune Polyglandular Syndrome Type 1 with Common Variable Immunodeficiency

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.152 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Yasamen Abdulmannan Shikdar ◽

Abdullah Almazrooa ◽

Shaza Samargandy

Keyword(s):

Common Variable Immunodeficiency ◽

Villous Atrophy ◽

Tissue Transglutaminase ◽

Iga Deficiency ◽

Primary Hypothyroidism ◽

Intestinal Biopsy ◽

Autoimmune Polyglandular Syndrome ◽

Autoimmune Polyglandular Syndrome Type ◽

Common Variable

Abstract BACKGROUND: Autoimmune polyglandular syndrome (APS) is a rare disorder. It’s co-existence with common variable immunodeficiency (CVID) was reported in 5 cases before but, none of them was APS type 1up to our knowledge. The overlap between the 2 conditions indicates a possible association between Autoimmunity and immunodeficiency. CLINICAL CASE: A 21-year-old lady was diagnosed to have CVID since infancy, as she was presenting to the hospital with recurrent infections and sepsis. At the age of 7 months, she was diagnosed with type 1 diabetes and was started on insulin. Furthermore, at 2 years of age she was found to have primary hypothyroidism and in her teenage she was diagnosed with primary adrenal insufficiency. Her history became more complicated when she also started to develop recurrent oral and esophageal candidiasis that required systemic anti-fungal therapy. Later in her life, she was incidentally found to have hypoparathyroidism when her labs showed hypocalcemia with inappropriately normal parathyroid hormone. She had chronic diarrhea which was thought to be due to celiac disease based on intestinal biopsy showing villous atrophy. With her IgA deficiency, her Tissue transglutaminase IgA antibodies were not reliable. Splenic atrophy was also detected on abdominal imaging. She never reached puberty and elected with her parents to not start combined hormonal therapy. With the constellation of these features, we concluded that she has type 1 APS along with CVID. CONCLUSION: Autoimmunity and immunodeficiency might be interconnected. Early diagnosis will affect the quality of life and early targeted treatment will prevent morbidity and early mortality. KEY WORDS: Autoimmune Polyglandular Syndrome, Common Variable Immunodeficiency.

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Celiac disease: Understandings in diagnostic, nutritional, and medicinal aspects

International Journal of Immunopathology and Pharmacology ◽

10.1177/20587384211008709 ◽

2021 ◽

Vol 35 ◽

pp. 205873842110087

Author(s):

Taoufik Ben Houmich ◽

Brahim Admou

Keyword(s):

Celiac Disease ◽

Villous Atrophy ◽

Current Trend ◽

Diagnostic Delay ◽

General Medicine ◽

Iga Deficiency ◽

Health Concern ◽

Intestinal Biopsy ◽

Antibody Testing ◽

Main Challenge

Celiac disease (CD) is characterized by clinical polymorphism, with classic, asymptomatic or oligosymptomatic, and extra-intestinal forms, which may lead to diagnostic delay and exposure to serious complications. CD is a multidisciplinary health concern involving general medicine, pediatric, and adult gastroenterology, among other disciplines. Immunology and pathology laboratories have a fundamental role in diagnosing and monitoring CD. The diagnosis consists of serological testing based on IgA anti-transglutaminase (TG2) antibodies combined with IgA quantification to rule out IgA deficiency, a potential misleading factor of CD diagnosis. Positive TG2 serology should be corroborated by anti-endomysium antibody testing before considering an intestinal biopsy. Owing to multiple differential diagnoses, celiac disease cannot be confirmed based on serological positivity alone, nor on isolated villous atrophy. In children with classical signs or even when asymptomatic, with high levels of CD-linked markers and positive HLA DQ2 and/or DQ8 molecules, the current trend is to confirm the diagnosis on basis of the non-systematic use of the biopsy, which remains obligatory in adults. The main challenge in managing CD is the implementation and compliance with a gluten-free diet (GFD). This explains the key role of the dietitian and the active participation of patients and their families throughout the disease-management process. The presence of the gluten in several forms of medicine requires the sensitization of physicians when prescribing, and particularly when dispensing gluten-containing formulations by pharmacists. This underlines the importance of the contribution of the pharmacist in the care of patients with CD within the framework of close collaboration with physicians and nutritionists.

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Nutritional Management of Celiac Disease

10.2310/tywc.9036 ◽

2018 ◽

Author(s):

Ciarán P Kelly ◽

Satya Kurada ◽

Mariana Urquiaga

Keyword(s):

Immune Response ◽

Celiac Disease ◽

Tight Junction ◽

Villous Atrophy ◽

Gastrointestinal Symptoms ◽

Gluten Free Diet ◽

Intestinal Biopsy ◽

Nutritional Management ◽

Gluten Free ◽

Antigliadin Antibodies

Celiac disease (CD) is an autoimmune disorder characterized by an immune response to gluten peptides in wheat, barley, and rye. The diagnosis of celiac disease is confirmed by three important characteristics: consistent symptoms, positive celiac-specific serology, and small intestinal biopsy findings of inflammation, crypt hyperplasia, and villous atrophy. CD may present with overt gastrointestinal symptoms, including diarrhea (or constipation), weight loss, and abdominal bloating and discomfort, or covertly with micronutrient deficiencies such as iron deficiency with anemia. A gluten-free diet (GFD) remains the mainstay of treatment. The aim of this review is to highlight the pathogenesis of CD, concepts and challenges associated with a GFD, and nutritional management of CD applicable in clinical practice to internists, gastroenterologists, and dietitians. Patients should be referred to an expert celiac dietitian for education on adherence to a GFD to address gluten contamination in the diet, the psychosocial implications of following a GFD, and macro- and micronutrient disequilibria arising from celiac disease and the GFD. Several novel therapeutics are on the horizon in various stages of development, including glutenases, antigliadin antibodies, tight junction regulators, modulation of the immune response to gliadin, and efforts to engineer less toxic gluten-containing foodstuffs. This review contains 3 figures, 5 tables, and 61 references. Key words: celiac disease, genetic engineering, food engineering, gluten, glutenases, gluten-free diet, oats, IgY, nutrition, tight junction regulators, wheat

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Relationships between Clinical Presentation, Serology, Histology, and Duodenal Deposits of Tissue Transglutaminase Antibodies in Pediatric Celiac Disease

Digestive Diseases ◽

10.1159/000490377 ◽

2018 ◽

Vol 36 (5) ◽

pp. 369-376 ◽

Cited By ~ 1

Author(s):

Nurit Loberman-Nachum ◽

Michael Schvimer ◽

Camila Avivi ◽

Iris Barshack ◽

Avishay Lahad ◽

...

Keyword(s):

Celiac Disease ◽

Immunohistochemical Staining ◽

Clinical Presentation ◽

Tissue Transglutaminase ◽

Mucosal Damage ◽

High Serum ◽

Tissue Transglutaminase Antibodies ◽

Antibody Levels ◽

Age Range ◽

Multiple Symptoms

Background: The clinical, histological, and serological spectrum of celiac disease (CD) vary widely. We aimed to examine relationships between symptoms, serum anti-tissue transglutaminase antibodies (tTG) levels, mucosal damage, and mucosal anti-tTG deposits in pediatric CD. Methods: A retrospective single-center, cohort study of children referred for endoscopy with suspected CD during 2011–2014. We retrieved the clinical data, blindly reviewed duodenal biopsies, and performed immunohistochemical staining for anti-tTG deposits. Patients were classified as monosymptomatic or polysymptomatic. Mucosal anti-tTG deposits were classified according to the location of deposits, dominant intensity, maximal intensity, and percentage of stained area. Results: Of 252 patients with confirmed CD, complete data were available for 100: 37 males in the age range 1.3–16.7 with median 4.0 years. Monosymptomatic patients (n = 54) presented at an older age than polysymptomatic patients (1.3–15.5, median 8.1 vs. 1.3–16.7, median 6.3 years, p = 0.026). Marsh 2–3c was more prevalent in polysymptomatic patients (93 vs. 78%, p = 0.028). The intensity of mucosal anti-tTG deposits correlated with serum anti-tTG levels but not with the clinical presentation. Conclusions: Multiple symptoms and high serum anti-tTG antibody levels correlated with mucosal damage in children with CD. The role of immunohistochemical staining for intestinal anti-tTG mucosal deposits in the diagnosis of borderline CD is not yet established.

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Simultaneous Detection of Drug-Induced Liver Injury Protein and microRNA Biomarkers Using Dynamic Chemical Labelling on a Luminex MAGPIX System

Analytica ◽

10.3390/analytica2040013 ◽

2021 ◽

Vol 2 (4) ◽

pp. 130-139

Author(s):

Antonio Marín-Romero ◽

Mavys Tabraue-Chávez ◽

Bárbara López-Longarela ◽

Mario A. Fara ◽

Rosario M. Sánchez-Martín ◽

...

Keyword(s):

Liver Injury ◽

Simultaneous Detection ◽

Single Step ◽

Qualitative And Quantitative Analysis ◽

Serum Samples ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Qualitative And Quantitative ◽

Post Marketing ◽

Mechanistic Basis

Drug-induced liver injury (DILI) is a potentially fatal adverse event and a leading cause for pre- and post-marketing drug withdrawal. Several multinational DILI initiatives have now recommended a panel of protein and microRNA (miRNA) biomarkers that can detect early liver injury and inform about mechanistic basis. This manuscript describes the development of seqCOMBO, a unique combo-multiplexed assay which combines the dynamic chemical labelling approach and an antibody-dependant method on the Luminex MAGPIX system. SeqCOMBO enables a versatile multiplexing platform to perform qualitative and quantitative analysis of proteins and miRNAs in patient serum samples simultaneously. To the best of our knowledge, this is the first method to profile protein and miRNA biomarkers to diagnose DILI in a single-step assay.

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Testing for Gluten-Related Disorders in Clinical Practice: The Role of Serology in Managing the Spectrum of Gluten Sensitivity

Canadian Journal of Gastroenterology ◽

10.1155/2011/642452 ◽

2011 ◽

Vol 25 (4) ◽

pp. 193-197 ◽

Cited By ~ 21

Author(s):

David Armstrong ◽

Andrew C Don-Wauchope ◽

Elena F Verdu

Keyword(s):

Celiac Disease ◽

Serological Test ◽

Tissue Transglutaminase ◽

Immunoglobulin A ◽

Intestinal Damage ◽

Gluten Sensitivity ◽

Serological Testing ◽

Diet Compliance ◽

At Risk Populations ◽

Irritable Bowel

Immunoglobulin A tissue transglutaminase is the single most efficient serological test for the diagnosis of celiac disease. It is well known that immunoglobulin A tissue transglutaminase levels correlate with the degree of intestinal damage, and that values can fluctuate in patients over time. Serological testing can be used to identify symptomatic individuals that need a confirmatory biopsy, to screen at-risk populations or to monitor diet compliance in patients previously diagnosed with celiac disease. Thus, interpretation of serological testing requires consideration of the full clinical scenario. Antigliadin tests are no longer recommended for the diagnosis of classical celiac disease. However, our understanding of the pathogenesis and spectrum of gluten sensitivity has improved, and gluten-sensitive irritable bowel syndrome patients are increasingly being recognized. Studies are needed to determine the clinical utility of antigliadin serology in the diagnosis of gluten sensitivity.

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Simultaneous Detection of Eight Analytes in Human Serum by Two Commercially Available Platforms for Multiplex Cytokine Analysis

Clinical and Vaccine Immunology ◽

10.1128/cvi.00211-07 ◽

2007 ◽

Vol 15 (1) ◽

pp. 42-48 ◽

Cited By ~ 59

Author(s):

Gary Toedter ◽

Karen Hayden ◽

Carrie Wagner ◽

Carrie Brodmerkel

Keyword(s):

Simultaneous Detection ◽

Tissue Level ◽

Careful Examination ◽

Serum Samples ◽

Meso Scale Discovery ◽

Necrosis Factor Alpha ◽

Monocyte Chemoattractant Protein 1 ◽

Inflammatory Protein ◽

Cytokine Analysis ◽

Endothelial Growth Factor

ABSTRACT The accurate detection and quantitation of cytokines in serum are important in the study of disease mechanisms, pathogenesis, and treatment. Serum cytokines can reflect processes that are occurring at the cellular or tissue level and thus provide a means of indirectly monitoring these processes. Multiplex detection of cytokines allows the simultaneous measurement of multiple cytokines in a sample, increasing the efficiency of measuring the cytokines while reducing the serum sample volumes required for the testing. Two commercially available multiplex platforms were evaluated (Pierce SearchLight and Meso Scale Discovery), using multiplexes capable of simultaneously detecting eight cytokines. The cytokines analyzed in this study were gamma interferon, vascular endothelial growth factor, tumor necrosis factor alpha, interleukin-6 (IL-6), macrophage inflammatory protein 1β, monocyte chemoattractant protein 1, IL-12p40, and IL-4. The range of quantitation of the platforms, the recovery of spiked cytokines, and the detection of the cytokines in serum samples from subjects with ulcerative colitis, Crohn's disease, rheumatoid arthritis, and psoriasis were examined. The findings showed that the detection of the cytokines was highly dependent upon the platform, with the consistency of the detection of cytokines across platforms being dependent upon the cytokine being analyzed. A careful examination of platform assay performance must be made prior to utilizing multiplex platforms in a study. While some cytokines will give similar patterns of results across platforms, others will be highly variable. The use of the same platform within a study or across studies where data will be compared is advised.

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Nutritional Management of Celiac Disease

10.2310/im.9036 ◽

2017 ◽

Author(s):

Ciarán P Kelly ◽

Satya Kurada ◽

Mariana Urquiaga

Keyword(s):

Immune Response ◽

Celiac Disease ◽

Tight Junction ◽

Villous Atrophy ◽

Gastrointestinal Symptoms ◽

Gluten Free Diet ◽

Intestinal Biopsy ◽

Nutritional Management ◽

Gluten Free ◽

Antigliadin Antibodies

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SEROLOGICAL SCREENING FOR CELIAC DISEASE IN CHILDREN WITH COLCHICINE-RESISTANT FAMILIAL MEDITERRANEAN FEVER

Arquivos de Gastroenterologia ◽

10.1590/s0004-2803.201800000-31 ◽

2018 ◽

Vol 55 (2) ◽

pp. 175-178

Author(s):

Yasin ŞAHIN ◽

Kenan BARUT ◽

Tufan KUTLU ◽

Fugen Cullu COKUGRAS ◽

Amra ADROVIC ◽

...

Keyword(s):

Celiac Disease ◽

Familial Mediterranean Fever ◽

Tissue Transglutaminase ◽

Intestinal Biopsy ◽

Control Group ◽

Serological Screening ◽

Iga Antibodies ◽

Mediterranean Fever ◽

Iga Antibody ◽

Clinical Conditions

ABSTRACT BACKGROUND: Familial Mediterranean fever and celiac disease share some common clinical features such as abdominal pain, diarrhea, arthralgia and arthritis. Also, both of the diseases are associated with many inflammatory and autoimmune diseases. Previous studies have shown the association between familial Mediterranean fever (FMF) and different clinical conditions. OBJECTIVE: We aimed to investigate the relationship between celiac disease and colchicine-resistant familial Mediterranean fever (crFMF) disease. METHODS: This prospective study was conducted at the Department of Pediatric Gastroenterology and Pediatric Rheumatology from October 2015 to August 2016. A total of 24 patients with crFMF were included in the study. We used 60 sex- and age-matched healthy subjects as a control group. Levels of total IgA and tissue transglutaminase (tTG) IgA antibody were measured in both groups. Those with increased level of tTG IgA were tested for anti-endomysium IgA antibodies (EMA). Gastroduodenoscopy and intestinal biopsy were planned for a definite diagnosis of celiac disease in patients with positive EMA. RESULTS: Of the 24 patients in this study, 18 (75.0%) were female. Only 4 (16.6%) of 24 patients were positive for tTG IgA. Patients with positive tTG IgA were then tested for EMA IgA antibodies and none of them had a positive result. Only one (1.6%) subject from the control group was positive for tTG IgA but EMA positivity was not detected. CONCLUSION: We did not found celiac disease in 24 children with crFMF. Since crFMF disease is rarely seen in general population, further studies with more patients are needed to provide more precise interpretation.

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The Broad Spectrum of Celiac Disease and Gluten Sensitive Enteropathy

Medicine and Pharmacy Reports ◽

10.15386/cjmed-698 ◽

2016 ◽

Vol 89 (3) ◽

pp. 335-342 ◽

Cited By ~ 3

Author(s):

Oana Mocan ◽

Dan L. Dumitrașcu

Keyword(s):

Celiac Disease ◽

Viral Infections ◽

Villous Atrophy ◽

Intraepithelial Lymphocytes ◽

Intestinal Biopsy ◽

Gluten Free ◽

Serological Tests ◽

Genetic Transmission ◽

Intestinal Involvement ◽

Gluten Sensitive Enteropathy

The celiac disease is an immune chronic condition with genetic transmission, caused by the intolerance to gluten. Gluten is a protein from cereals containing the following soluble proteins: gliadine, which is the most toxic, and the prolamins. The average prevalence is about 1% in USA and Europe, but high in Africa: 5.6% in West Sahara. In the pathogenesis several factors are involved: gluten as external trigger, genetic predisposition (HLA, MYO9B), viral infections, abnormal immune reaction to gluten. Severity is correlated with the number of intraepithelial lymphocytes, cryptic hyperplasia and villous atrophy, as well as with the length of intestinal involvement. The severity is assessed according to the Marsh–Oberhuber staging. Diagnostic criteria are: positive serological tests, intestinal biopsy, the reversal after gluten free diet (GFD). Beside refractory forms, new conditions have been described, like the non celiac gluten intolerance. In a time when more and more people adhere to GFD for nonscientific reasons, practitioners should be updated with the progress in celiac disease knowledge.

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