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Stahl MG, Pan Z, Germone M, Nagle S, Mehta P, Shull M, Griffith I, Shuler B, Hoffenberg E, Taki I, Geno-Rasmussen C, Rewers MJ, Norris JM, Liu E, ASK Study Group. One-Year Outcomes Among Children Identified With Celiac Disease Through a Mass Screening Program. Clin Gastroenterol Hepatol 2025; 23:1135-1142. [PMID: 38615728 DOI: 10.1016/j.cgh.2024.03.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 03/02/2024] [Accepted: 03/11/2024] [Indexed: 04/16/2024]
Abstract
BACKGROUND & AIMS Celiac disease (CD) mass screening remains controversial in part because of a paucity of data to support its benefit. The Autoimmunity Screening for Kids study is a mass screening study for pediatric CD and type 1 diabetes in Colorado. METHODS This study prospectively follows up children ages 1 to 17 years who screened positive for tissue transglutaminase IgA autoantibodies in the Autoimmunity Screening for Kids study subsequently referred for diagnostic evaluation. Children diagnosed with CD by biopsy or serologic criteria were included in this study. Evaluation at baseline and 12 month follow-up evaluation included demographics, laboratory studies, symptoms, health-related quality of life, anxiety/depression, and gluten-free diet adherence. Paired Student t test, chi-square, and Wilcoxon signed-rank tests compared baseline and follow-up data. For symptom scores, odds of improvement were assessed. RESULTS Of the 52 children with CD enrolled, 42 children completed 12-month follow-up evaluation. On the symptom questionnaire completed at diagnostic evaluation, 38 of 42 children reported 1 or more symptoms. CD mean symptom severity and frequency scores improved from baseline to follow-up evaluation (P < .001). Reported health-related quality of life scores improved among caregivers (P = .002). There was no significant change in reported anxiety or depression. Iron deficiency without anemia was common at baseline (21 of 24 children; 87.5%) and normalized at follow-up evaluation (11 of 21 children; 52.3%). Twenty-six of 28 families reported good or excellent gluten-free diet adherence. CONCLUSIONS This novel study of children with CD identified through a mass screening program demonstrated improvement in symptoms, quality of life, and iron deficiency after 1 year follow-up evaluation. This demonstrates that there may be benefit to CD mass screening.
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Affiliation(s)
- Marisa G Stahl
- Digestive Health Institute, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
| | - Zhaoxing Pan
- Child Health Research Biostatistics Core, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Monique Germone
- Digestive Health Institute, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Sadie Nagle
- Digestive Health Institute, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Pooja Mehta
- Digestive Health Institute, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Mary Shull
- Digestive Health Institute, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Isabel Griffith
- Digestive Health Institute, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Brianne Shuler
- Digestive Health Institute, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Edward Hoffenberg
- Digestive Health Institute, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Iman Taki
- Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Cristy Geno-Rasmussen
- Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Marian J Rewers
- Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Jill M Norris
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Edwin Liu
- Digestive Health Institute, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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du Pre MF, Iversen R, Sollid LM. Coeliac disease: the paradox of diagnosing a food hypersensitivity disorder with autoantibodies. Gut 2024; 73:844-853. [PMID: 38378252 DOI: 10.1136/gutjnl-2023-331595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 01/30/2024] [Indexed: 02/22/2024]
Abstract
Serum antibodies to the autoantigen transglutaminase 2 (TG2) are increasingly harnessed to diagnose coeliac disease. Diagnostic guidelines for children give recommendation for a no-biopsy-based diagnosis through detection of high amounts of IgA anti-TG2 antibodies in serum with confirmation of positivity in a separate blood sample by characteristic autoantibody-staining of tissue. While measurement of IgA anti-TG2 also is important in the diagnostic workup of adults, the adult guidelines still mandate examination of gut biopsies. This requirement might well change in the future, as might the necessity for confirming autoantibody positivity by tissue staining. The key role of autoantibody serology for diagnosis of coeliac disease is paradoxical. Coeliac disease was considered, and still can be considered, a food intolerance disorder where autoantibodies at face value are out of place. The immunological mechanisms underlying the formation of autoantibodies in response to gluten exposure have been dissected. This review presents the current insights demonstrating that the autoantibodies in coeliac disease are intimately integrated in the maladapted immune response to gluten.
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Affiliation(s)
- M Fleur du Pre
- Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Immunology, Oslo University Hosptial - Rikshospitalet, Oslo, Norway
| | - Rasmus Iversen
- Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Immunology, Oslo University Hosptial - Rikshospitalet, Oslo, Norway
| | - Ludvig M Sollid
- Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Immunology, Oslo University Hosptial - Rikshospitalet, Oslo, Norway
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Jansson-Knodell CL, Rubio-Tapia A. Gluten-related Disorders From Bench to Bedside. Clin Gastroenterol Hepatol 2024; 22:693-704.e1. [PMID: 37879521 DOI: 10.1016/j.cgh.2023.09.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 09/26/2023] [Accepted: 09/29/2023] [Indexed: 10/27/2023]
Abstract
Celiac disease, non-celiac gluten sensitivity, and wheat allergy comprise 3 of the main conditions with wheat- and gluten-containing foods as the symptom trigger. Distinguishing between these entities can be daunting. In this review, we compare and contrast celiac disease, non-celiac gluten sensitivity, and wheat allergy to allow clinicians to determine which diagnosis fits their patient to facilitate high-quality management and longitudinal care.
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Affiliation(s)
- Claire L Jansson-Knodell
- Celiac Disease Program, Division of Gastroenterology, Hepatology, and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Alberto Rubio-Tapia
- Celiac Disease Program, Division of Gastroenterology, Hepatology, and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio.
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Novis CL, Wahl E, Camacho E, Aure MA, Mahler M, Nandakumar V. Performance Assessment of a Novel Multianalyte Methodology for Celiac Disease Biomarker Detection and Evaluation of the Serology-Alone Criteria for Biopsy-Free Diagnosis. Arch Pathol Lab Med 2023; 147:1422-1430. [PMID: 36856668 DOI: 10.5858/arpa.2022-0385-oa] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/02/2022] [Indexed: 03/02/2023]
Abstract
CONTEXT.— Serology plays a vital role in celiac disease (CD) diagnosis, and the latest European guidelines advocate for biopsy-free diagnoses in patients with ≥10× the upper limit of normal (ULN) of anti-tissue transglutaminase (tTG) immunoglobulin A (IgA) antibodies. OBJECTIVE.— To assess performance characteristics of a novel automated particle-based multianalyte technology (Aptiva) for anti-tTG and anti-deamidated gliadin peptide (DGP) antibody detection as compared to the traditional enzyme-linked immunosorbent assay (QUANTA Lite). Performance characteristics of the ≥10× ULN anti-tTG IgA criteria for serologic diagnosis of CD were also evaluated. DESIGN.— Sera samples from 703 patients were tested for anti-tTG IgA, anti-tTG immunoglobulin G (IgG), anti-DGP IgA, and anti-DGP IgG antibodies on both platforms. In total, 127 patients had medical information and were classified as CD-positive (n = 58) and CD-negative (n = 69) based on biopsy results. Clinical performance characteristics were evaluated. RESULTS.— Anti-tTG IgA detection showed equal clinical sensitivity and specificity of 91% sensitivity and 99% specificity on both platforms. Anti-tTG IgG resulted in moderate sensitivity of 69% and 72%, but high specificity of 100% and 94% on Aptiva and QUANTA Lite, respectively. Anti-DGP IgG displayed comparable sensitivity of 90% and 81%, and a specificity of 94% and 99%, on Aptiva and QUANTA Lite, respectively. Anti-DGP IgA demonstrated greater sensitivity on QUANTA Lite (83%) than Aptiva (69%) and similar specificities of 97% and 98% on QUANTA Lite and Aptiva, respectively. At ≥10× ULN levels for anti-tTG IgA, Aptiva displayed a sensitivity of 72% and a specificity of 100%, and QUANTA Lite showed a sensitivity of 69% and a specificity of 100%. CONCLUSIONS.— Aptiva is a reliable method to measure CD biomarkers with reduced hands-on necessity and high-throughput capabilities. This study supports the use of a ≥10× ULN anti-tTG IgA biopsy-free approach for serologic diagnosis of CD.
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Affiliation(s)
- Camille Leite Novis
- From the ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah (Novis, Nandakumar)
| | - Edward Wahl
- Research and Development, Headquarters and Technology Center Autoimmunity, Werfen, San Diego, California (Wahl, Camacho, Aure, Mahler)
| | - Eric Camacho
- Research and Development, Headquarters and Technology Center Autoimmunity, Werfen, San Diego, California (Wahl, Camacho, Aure, Mahler)
| | - Mary Ann Aure
- Research and Development, Headquarters and Technology Center Autoimmunity, Werfen, San Diego, California (Wahl, Camacho, Aure, Mahler)
| | - Michael Mahler
- Research and Development, Headquarters and Technology Center Autoimmunity, Werfen, San Diego, California (Wahl, Camacho, Aure, Mahler)
| | - Vijayalakshmi Nandakumar
- From the ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah (Novis, Nandakumar)
- The Department of Pathology, University of Utah School of Medicine, Salt Lake City (Nandakumar)
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Tiberti C, Bonamico M, Nenna R, Petrarca L, Trovato CM, Pietropaoli N, Fassino V, Midulla F, Lenzi A, Oliva S, Montuori M. Investigating the Relationship Between COVID-19 and Celiac Disease. A Dual Research Approach. JPGN REPORTS 2023; 4:e340. [PMID: 38034464 PMCID: PMC10684164 DOI: 10.1097/pg9.0000000000000340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 06/09/2023] [Indexed: 12/02/2023]
Abstract
Background Most evidence on the coronavirus disease 2019 (COVID-19) pandemic, has been obtained from web- or telephone-based surveys. In particular, few laboratory data, often incomplete, have been reported on the frequency of COVID-19-related serology at celiac disease (CD) diagnosis or on the effects of COVID-19 on the development of CD-specific autoimmunity. Objectives The objective of this retrospective cross-sectional case/control study was to: (1) evaluate the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in 78 children and adolescents at CD diagnosis (CD, 44 females, median age 7.4 years); (2) evaluate the frequency of IgA-anti-transglutaminase antibodies (IgA-tTGAbs) in 97 nonceliac patients (50 females, median age 9.0 years) who contracted SARS-CoV-2 infection during the pandemic (February-April 2021). As a control (CTRL) group, we analyzed 141 healthy subjects (79 females, median age 9.8 years) enrolled during the pandemic. Methods SARS-CoV-2 IgM- and IgG-antibodies were detected by chemiluminescent microparticle immunoassays. IgA-tTGAbs were detected by a fluid-phase radioimmunoassay. Results Six out of 78 (7.7%) CD patients tested positive for SARS-CoV-2Abs, with a frequency not significantly different from CTRL subjects (9.2%). None of the 97 nonceliac COVID-19 patients tested positive for IgA-tTG antibodies. Conclusion These 2 distinct research approaches showed (1) similar frequencies of SARS-CoV-2 immunoreactivities in CD patients and CTRL subjects and, (2) no ability of SARS-CoV-2 to induce a CD-specific immune response, at least in the 3-4 months following SARS-CoV-2 infection.
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Affiliation(s)
| | | | | | - Laura Petrarca
- Department of Maternal, Infantile and Urological Sciences
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Italy
| | - Chiara Maria Trovato
- Department of Maternal, Infantile and Urological Sciences
- Hepatology Gastroenterology and Nutrition Unit, Bambino Gesù Children Hospital, Rome, Italy
| | | | | | - Fabio Midulla
- Department of Maternal, Infantile and Urological Sciences
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Vauquelin B, Rivière P. [Celiac disease]. Rev Med Interne 2023; 44:539-545. [PMID: 37558601 DOI: 10.1016/j.revmed.2023.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 06/12/2023] [Accepted: 07/25/2023] [Indexed: 08/11/2023]
Abstract
Celiac disease is a frequent auto-immune disease characterized by villous atrophy related to gluten intake in patients with genetic susceptiblity. Patients do not present symptoms in the majority of cases. Presence of the disease must be investigated in case of digestive symptoms or presence of auto-immune disease. Diagnosis is based on anti-transglutaminase antibody and dudodenal biospies. The only available treatment is gluten-free diet. Associated auto-immune diseases must be investigated, especially thyroiditis. Complications related to nutritional deficiency must be accounted for also.
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Affiliation(s)
- B Vauquelin
- Service d'hépato-gastroentérologie et oncologie digestive, centre médico-chirurgical Magellan, CHU de Bordeaux, Bordeaux, France
| | - P Rivière
- Service d'hépato-gastroentérologie et oncologie digestive, centre médico-chirurgical Magellan, CHU de Bordeaux, Bordeaux, France.
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Tiberti C, Nenna R, Tromba V, Filardi T, Petrarca L, Silvestri F, Fassino V, Montuori M, Mancino E, Lenzi A, Midulla F, Costantino F, Morano S. No effects of COVID-19 on the development of type 1 diabetes autoimmunity and no evidence of an increased frequency of SARS-CoV-2 antibodies in newly diagnosed type 1 diabetes patients relative to healthy subjects. Acta Diabetol 2023; 60:1301-1307. [PMID: 37171699 PMCID: PMC10175916 DOI: 10.1007/s00592-023-02103-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 01/07/2023] [Indexed: 05/13/2023]
Abstract
AIMS To evaluate the relationship between SARS-CoV-2 infection and autoimmunity in type 1 diabetes (T1D) and SARS-CoV-2 antibodies frequency at diagnosis of T1D during pandemic. METHODS The presence of T1D-specific autoimmunity was evaluated in a cohort of 99 children and adolescents without diabetes that contracted SARS-CoV-2 infection. Moreover, the frequency of IgM- and IgG-SARS-CoV-2 antibodies was evaluated in 41 newly diagnosed T1D patients not yet vaccinated against SARS-CoV-2 disease, collected during the pandemic, compared to healthy subjects (CTRL). RESULTS None of the 99 patients that contracted SARS-CoV-2 infection during the pandemic period was found positive for T1D autoantibodies. The frequency of SARS-CoV-2 antibodies was not significantly different in patients newly diagnosed with T1D (12.2%), compared with CTRL (8.4%). Among SARS-CoV-2 antibody positive T1D patients, 80% were target of diabetes autoantibodies and 60% had another concomitant autoimmune disease. Among the CTRL subjects positive for SARS-CoV-2Abs (n = 10), none was found positive for T1D autoantibodies. CONCLUSIONS The results of the present study do not confirm, at least in the short term, a role of COVID-19 as a potential trigger of T1D autoimmunity and do not provide evidence of an increased frequency of SARS-CoV-2 antibodies in newly diagnosed T1D patients in comparison with healthy population.
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Affiliation(s)
- Claudio Tiberti
- Department of Experimental Medicine, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
| | - Raffaella Nenna
- Department of Maternal, Infantile and Urological Sciences, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
| | - Valeria Tromba
- Department of Maternal, Infantile and Urological Sciences, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
| | - Tiziana Filardi
- Department of Experimental Medicine, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
| | - Laura Petrarca
- Department of Maternal, Infantile and Urological Sciences, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
| | - Francesca Silvestri
- Department of Maternal, Infantile and Urological Sciences, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
| | - Valeria Fassino
- Department of Experimental Medicine, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
| | - Monica Montuori
- Department of Maternal, Infantile and Urological Sciences, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
| | - Enrica Mancino
- Department of Maternal, Infantile and Urological Sciences, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
| | - Andrea Lenzi
- Department of Experimental Medicine, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
| | - Fabio Midulla
- Department of Maternal, Infantile and Urological Sciences, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
| | - Francesco Costantino
- Department of Maternal, Infantile and Urological Sciences, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
| | - Susanna Morano
- Department of Experimental Medicine, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
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Corrado MM, Jia X, Geno Rasmussen C, Pyle L, Yu L, Liu E, Stahl M, Rewers MJ. Previous SARS-CoV-2 Infection Is Not Associated With Increased Celiac Disease Autoimmunity in Children and Adolescents. Am J Gastroenterol 2023; 118:1698-1700. [PMID: 37159249 DOI: 10.14309/ajg.0000000000002317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 04/27/2023] [Indexed: 05/10/2023]
Abstract
INTRODUCTION Recent reports suggest severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections may increase the risk of celiac disease autoimmunity. This study aims to evaluate potential associations between coronavirus disease 2019 infection and tissue transglutaminase autoantibodies (TGA) immunoglobulin A. METHODS From 2020 to 2021, cross-sectional screening for SARS-CoV-2 antibodies and TGA was offered to 4,717 children in Colorado through the Autoimmunity Screening for Kids study. Multivariable logistic regression assessed association between previous SARS-CoV-2 infection and TGA positivity. RESULTS Previous SARS-CoV-2 infection was not associated with TGA positivity (odds ratio 1.02, 95% confidence interval 0.63-1.59; P = 0.95). DISCUSSION In this large-scale analysis, previous SARS-CoV-2 infection was not associated with celiac disease autoimmunity in Colorado children.
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Affiliation(s)
- Michelle M Corrado
- Digestive Health Institute, Children's Hospital Colorado, University of Colorado, Aurora, Colorado, USA
| | - Xiaofan Jia
- Barbara Davis Center for Diabetes, University of Colorado, Aurora, Colorado, USA
| | | | - Laura Pyle
- Barbara Davis Center for Diabetes, University of Colorado, Aurora, Colorado, USA
| | - Liping Yu
- Barbara Davis Center for Diabetes, University of Colorado, Aurora, Colorado, USA
| | - Edwin Liu
- Digestive Health Institute, Children's Hospital Colorado, University of Colorado, Aurora, Colorado, USA
| | - Marisa Stahl
- Digestive Health Institute, Children's Hospital Colorado, University of Colorado, Aurora, Colorado, USA
| | - Marian J Rewers
- Barbara Davis Center for Diabetes, University of Colorado, Aurora, Colorado, USA
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Alexander L, Rasmus B, Charlotte B, Daniel A. Antibody detection by agglutination-PCR (ADAP) assays for the analysis of tissue transglutaminase autoantibodies in celiac disease. J Immunol Methods 2023:113502. [PMID: 37257686 DOI: 10.1016/j.jim.2023.113502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 05/14/2023] [Accepted: 05/25/2023] [Indexed: 06/02/2023]
Abstract
BACKGROUND & AIMS Tissue 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 determination by agglutination-PCR (ADAP) assay for the detection of tTGA. METHODS Included 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. RESULTS ADAP 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 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. CONCLUSIONS No 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.
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Affiliation(s)
- Lind Alexander
- Department of Clinical Sciences Malmö, Lund University, Sweden.
| | - Bennet Rasmus
- Department of Clinical Sciences Malmö, Lund University, Sweden
| | | | - Agardh Daniel
- Department of Clinical Sciences Malmö, Lund University, Sweden
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10
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Brady RP, Jensen ET, Rigdon J, Crimmins NA, Mallon D, Dolan LM, Imperatore G, Kahkoska AR, Mottl AK, Honor A, Pettitt DJ, Merjaneh L, Dabelea D, Shah AS. The Frequency of Undiagnosed Celiac Disease in Youth with Type 1 Diabetes and Its Association with Diabetic Retinopathy: The SEARCH for Diabetes in Youth Study. Pediatr Diabetes 2023; 2023:9038795. [PMID: 39845332 PMCID: PMC11753297 DOI: 10.1155/2023/9038795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 02/07/2023] [Accepted: 05/08/2023] [Indexed: 01/24/2025] Open
Abstract
Aims Celiac disease (CD) in adults with type 1 diabetes has been associated with increased cardiovascular risk and the earlier occurrence of diabetes-associated complications. In the Search for Diabetes in Youth study, we aimed to assess the frequency of CD and the potential for undiagnosed CD among youth with childhood onset type 1 diabetes. In addition, we assessed the burden of cardiovascular risk factors and diabetes-associated complications in youth with type 1 diabetes by CD status and IgA tissue transglutaminase autoantibody (tTGA) levels. Methods 2,444 youths with type 1 diabetes completed a CD questionnaire and underwent tTGA testing. Integrating the celiac disease questionnaire and tTGA results for this cross-sectional analysis, participants were categorized as follows: (1) reported CD; (2) seropositive for CD (no reported CD and seropositive tTGA); and (3) type 1 diabetes only (comparison group: no reported CD and seronegative tTGA). Subanalyses were performed on those with no reported CD and tTGA ≥10x ULN, designated potentially undiagnosed CD. Cardiovascular risk factors and diabetes-associated complications were evaluated by CD status and tTGA levels utilizing a Poisson model to estimate relative risk. Results Reported CD in youths with type 1 diabetes was 7%. Seropositivity for tTGA with no reported CD was present in 4%, and 1.2% had potentially undiagnosed CD. Youths with potentially undiagnosed CD had a 2.69x higher risk of diabetic retinopathy than comparison group. In addition, CD with tTGA <0.05 (controlled CD) was associated with lower HbA1c. Conclusions Undiagnosed CD is likely present in youths with type 1 diabetes and potentially undiagnosed CD is associated with a higher risk of diabetic retinopathy. These findings indicate the importance of routine screening for CD in type 1 diabetes in youths.
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Affiliation(s)
- Ryan P. Brady
- Department of Pediatrics, Cincinnati Children's Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Elizabeth T. Jensen
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Joseph Rigdon
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Nancy A. Crimmins
- Department of Pediatrics, Cincinnati Children's Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Daniel Mallon
- Department of Pediatrics, Cincinnati Children's Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Lawrence M. Dolan
- Department of Pediatrics, Cincinnati Children's Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Giuseppina Imperatore
- Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA
| | - Anna R. Kahkoska
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Amy K. Mottl
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Ann Honor
- Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | | | - Lina Merjaneh
- Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
| | - Dana Dabelea
- Lifeourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Departments of Epidemiology and Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Amy S. Shah
- Department of Pediatrics, Cincinnati Children's Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
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Ghazanfar H, Javed N, Lee S, Shaban M, Cordero D, Acherjee T, Hasan KZ, Jyala A, Kandhi S, Hussain AN, Patel H. Novel Therapies for Celiac Disease: A Clinical Review Article. Cureus 2023; 15:e39004. [PMID: 37323330 PMCID: PMC10263194 DOI: 10.7759/cureus.39004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/14/2023] [Indexed: 06/17/2023] Open
Abstract
Celiac disease is emerging as an autoimmune disorder with increasing prevalence and incidence. The mean age of presentation is also increasing with the passage of time. The delay in diagnosis is partly attributable to the asymptomatic state in which most patients present. The diagnosis of the disease is primarily based on biopsy, but serology can also be included for possible screening purposes. Although the primary management strategy is to eliminate gluten from the diet of such patients; however, compliance with the diet and follow-up to detect healing might be difficult to maintain. Therefore, there is a need to investigate further management therapies that can be easily administered and monitored. The aim of the review is to discuss the epidemiology, clinical presentation, and novel therapies being investigated for celiac disease.
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Affiliation(s)
| | - Nismat Javed
- Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Somin Lee
- Internal Medicine, BronxCare Hospital Center, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Mohammed Shaban
- Internal Medicine, BronxCare Hospital Center, Icahn School of Medicine at Mount Sinai, New York, USA
| | | | | | - Khushbu Z Hasan
- Internal Medicine, Mohtarma Benazir Bhutto Shaheed Medical College, Mirpur, PAK
| | | | - Sameer Kandhi
- Internal Medicine, BronxCare Health System, New York, USA
| | - Ali N Hussain
- Premedical, Baruch College, City University of New York, New York, USA
| | - Harish Patel
- Medicine/Gastroenterology, BronxCare Health System, New York, USA
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Seetharaman K, Lal SB, Prasad KK, Kumar Y, Bhatia A, Malhotra S. Role of Serology, Dietary Assessment, and Fecal Gluten Immunogenic Peptides for Predicting Histologic Recovery in Children with Celiac Disease. Dig Dis Sci 2023; 68:529-540. [PMID: 36459294 DOI: 10.1007/s10620-022-07762-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 11/07/2022] [Indexed: 12/03/2022]
Abstract
BACKGROUND A strict lifelong gluten-free diet (GFD) remains the only treatment of celiac disease (CD). Adherence to gluten-free diet is best reflected by mucosal healing. Noninvasive tools capable of predicting mucosal recovery in CD patients need to be identified. AIMS To compare the ability of various modalities used to assess compliance to GFD, for predicting persistent mucosal damage in children with CD. METHODS A prospective, single-center, observational study on children with CD on a GFD was conducted between January 2020 and April 2021. Children with CD on GFD were consecutively enrolled and various modalities used to assess adherence to GFD were compared. RESULTS One hundred and fifty children (Mean age 12.2 ± 3.6 years, 58% Boys) on GFD (Mean duration 6 ± 3.1 years) were enrolled in the study. Persistent mucosal damage was seen in 88% of the enrolled. Fecal gluten immunogenic peptide (GIP) was positive in 87.8% (129/147). Antibodies to tissue transglutaminase (TGA-IgA) and/or deamidated gliadin peptide (DGP) were positive in 32% (48/150) whereas antibody to synthetic neoepitopes of TGA-IgA was positive in 24.8% (37/149). Non-compliance as assessed by local questionnaire, Biagi score, and dietitian detailed interview were 62.7%, 60%, and 75.3%, respectively. Serology had the highest specificity (83%) and fecal GIP had the highest sensitivity (89%). On logistic regression analysis, only non-compliance by Biagi score predicted poor mucosal recovery. CONCLUSION Fecal GIP may be sensitive to detect only "one-point dietary transgression." None of the existing modalities used to assess compliance to GFD accurately predict persistent mucosal damage. A subset of patients may develop gluten tolerance.
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Affiliation(s)
- Keerthivasan Seetharaman
- Division of Pediatric Gastroenterology and Hepatology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India
| | - Sadhna Bhasin Lal
- Division of Pediatric Gastroenterology and Hepatology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India.
| | - Kaushal Kishor Prasad
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Yashwant Kumar
- Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Alka Bhatia
- Department of Experimental Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sunita Malhotra
- Department of Dietetics, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Is There a Need to Undertake Conventional Gastroscopy and Biopsy When Making the Diagnosis of Coeliac Disease in Adults? J Clin Gastroenterol 2023; 57:139-142. [PMID: 36598805 DOI: 10.1097/mcg.0000000000001806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Celiac disease is a common autoimmune condition characterized by small intestinal inflammation and mucosal damage triggered by an inappropriate immune response to ingested gluten. Gastroscopy and duodenal biopsy are currently the gold standard approach to diagnosing celiac disease in adults. However, the emergence of highly accurate serological tests for celiac disease in the last 2 decades led to a change in the pediatric guidelines to diagnose celiac disease without biopsy in selected patients. Adopting this no-biopsy approach to diagnose celiac disease in adults remains controversial, but the evidence supporting it is growing.
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Rubio-Tapia A, Hill ID, Semrad C, Kelly CP, Greer KB, Limketkai BN, Lebwohl B. American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease. Am J Gastroenterol 2023; 118:59-76. [PMID: 36602836 DOI: 10.14309/ajg.0000000000002075] [Citation(s) in RCA: 170] [Impact Index Per Article: 85.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 08/23/2022] [Indexed: 01/06/2023]
Abstract
This guideline presents an update to the 2013 American College of Gastroenterology Guideline on the Diagnosis and Management of Celiac Disease with updated recommendations for the evaluation and management of patients with celiac disease (CD). CD is defined as a permanent immune-mediated response to gluten present in wheat, barley, and rye. CD has a wide spectrum of clinical manifestations that resemble a multisystemic disorder rather than an isolated intestinal disease, and is characterized by small bowel injury and the presence of specific antibodies. Detection of CD-specific antibodies (e.g., tissue transglutaminase) in the serum is very helpful for the initial screening of patients with suspicion of CD. Intestinal biopsy is required in most patients to confirm the diagnosis. A nonbiopsy strategy for the diagnosis of CD in selected children is suggested and discussed in detail. Current treatment for CD requires strict adherence to a gluten-free diet (GFD) and lifelong medical follow-up. Most patients have excellent clinical response to a GFD. Nonresponsive CD is defined by persistent or recurrent symptoms despite being on a GFD. These patients require a systematic workup to rule out specific conditions that may cause persistent or recurrent symptoms, especially unintentional gluten contamination. Refractory CD is a rare cause of nonresponsive CD often associated with poor prognosis.
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Affiliation(s)
- Alberto Rubio-Tapia
- Division of Gastroenterology, Hepatology, and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Ivor D Hill
- Division of Gastroenterology, Hepatology, and Nutrition, Nationwide Children Hospital, Columbus, Ohio, USA
| | - Carol Semrad
- Division of Gastroenterology, University of Chicago, Chicago, Illinois, USA
| | - Ciarán P Kelly
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Katarina B Greer
- Department of Medicine, Section of Gastroenterology and Hepatology, Louis Stokes VA Medical Center, Cleveland, Ohio, USA
| | - Berkeley N Limketkai
- Division of Digestive Diseases, UCLA School of Medicine, Los Angeles, California, USA
| | - Benjamin Lebwohl
- Division of Gastroenterology and Hepatology, Columbia University, New York, USA
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15
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Infantino C, Francavilla R, Vella A, Cenni S, Principi N, Strisciuglio C, Esposito S. Role of Vitamin D in Celiac Disease and Inflammatory Bowel Diseases. Nutrients 2022; 14:nu14235154. [PMID: 36501183 PMCID: PMC9735899 DOI: 10.3390/nu14235154] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 11/30/2022] [Accepted: 11/30/2022] [Indexed: 12/12/2022] Open
Abstract
Vitamin D (VD) is a pro-hormone that has long been known as a key regulator of calcium homeostasis and bone health in both children and adults. In recent years, studies have shown that VD may exert many extra-skeletal functions, mainly through a relevant modulation of the innate and adaptive immune system. This has suggested that VD could play a fundamental role in conditioning development, clinical course, and treatment of several autoimmune disorders, including celiac disease (CD) and inflammatory bowel diseases (IBDs). The main aim of this review is to evaluate the relationships between VD, CD, and IBDs. Literature analysis showed a potential impact of VD on CD and IBDs can be reasonably assumed based on the well-documented in vitro and in vivo VD activities on the gastrointestinal tract and the immune system. The evidence that VD can preserve intestinal mucosa from chemical and immunological damage and that VD modulation of the immune system functions can contrast the mechanisms that lead to the intestinal modifications characteristic of gastrointestinal autoimmune diseases has suggested that VD could play a role in controlling both the development and the course of CD and IBDs. Administration of VD in already diagnosed CD and IBD cases has not always significantly modified disease course. However, despite these relevant problems, most of the experts recommend monitoring of VD levels in patients with CD and IBDs and administration of supplements in patients with hypovitaminosis.
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Affiliation(s)
- Claudia Infantino
- Department of Medicine and Surgery, Pediatric Clinic, University of Parma, 43126 Parma, Italy
| | - Roberta Francavilla
- Department of Medicine and Surgery, Pediatric Clinic, University of Parma, 43126 Parma, Italy
| | - Adriana Vella
- Department of Medicine and Surgery, Pediatric Clinic, University of Parma, 43126 Parma, Italy
| | - Sabrina Cenni
- Department of Woman, Child and General and Specialized Surgery, Second University of Naples, 80138 Naples, Italy
| | | | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialized Surgery, Second University of Naples, 80138 Naples, Italy
| | - Susanna Esposito
- Department of Medicine and Surgery, Pediatric Clinic, University of Parma, 43126 Parma, Italy
- Correspondence: ; Tel.: +39-0521-704-790
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Costantino A, Aversano GM, Lasagni G, Smania V, Doneda L, Vecchi M, Roncoroni L, Pastorello EA, Elli L. Diagnostic management of patients reporting symptoms after wheat ingestion. Front Nutr 2022; 9:1007007. [PMID: 36276818 PMCID: PMC9582535 DOI: 10.3389/fnut.2022.1007007] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 09/12/2022] [Indexed: 12/11/2022] Open
Abstract
Many patients report symptoms after wheat ingestion experiencing a wide spectrum of clinical manifestations. Three possible diagnoses have been recognized: celiac disease (CD), wheat allergy (WA), and non-celiac (gluten) wheat sensitivity (NCGS/NCWS). CD is a chronic immune-mediated disease of the small bowel caused by exposure to dietary gluten in genetically predisposed individuals, with a prevalence of approximately 1%. It is characterized by mucosal inflammation and atrophy following exposure to gluten and improvement after gluten withdrawal. Food allergies are immunological responses to a food antigen. WA is the expression of an immunologically mediated process that can be immunoglobulin E (IgE) or non-IgE mediated; its many symptoms include urticaria/angioedema, asthma, rhinitis, and anaphylaxis. NCGS/NCWS is characterized by gastrointestinal and/or extra-intestinal symptoms after ingestion of gluten-containing food in subjects not affected by CD or WA. The aim of this review is to help physicians and nutritionists diagnose the cause of symptoms reported after wheat ingestion, thus avoiding patient frustration, inappropriate testing, and incorrect or missed diagnoses. An algorithm for the diagnostic approach in these patients is provided, to help to diagnose CD, WA, NCGS/NCWS or to identify possible functional disorders as the wheat-sensitive irritable bowel syndrome. A personalized approach, regular follow-up, and the help of a skilled healthcare professional are mandatory for patients with symptoms following wheat ingestion is provided. A gluten-free-diet is often recommended for patients with self-reported gluten/wheat-dependent symptoms; for patients with symptoms similar to those of functional diseases while there is evidence that a low-FODMAP diet could be the first option.
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Affiliation(s)
- Andrea Costantino
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy,Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Gloria Maria Aversano
- Department of Internal Medicine, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Giovanni Lasagni
- Department of Allergology and Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Veronica Smania
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Luisa Doneda
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | - Maurizio Vecchi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy,Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Leda Roncoroni
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | | | - Luca Elli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy,*Correspondence: Luca Elli,
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17
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Singh AD, Ellias S, Singh P, Ahuja V, Makharia GK. The Prevalence of the Celiac Disease in Patients with Dyspepsia: A Systematic Review and Meta-Analysis. Dig Dis Sci 2022; 67:3067-3079. [PMID: 34268659 DOI: 10.1007/s10620-021-07142-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Accepted: 06/28/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Patients with celiac disease (CeD) can commonly present with symptoms of dyspepsia. We conducted a systematic review and meta-analysis of the present literature to assess the prevalence of CeD in patients diagnosed with dyspepsia. METHODS We searched MEDLINE and EMBASE databases for the keywords: celiac disease, coeliac disease, anti-gliadin, tissue transglutaminase antibody, anti-endomysial antibody, dyspepsia and functional gastrointestinal disorder. All the studies published from January 1991 till May 2021 were included. Diagnosis of CeD was based on the European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines. A random-effects model was used to pool the data. RESULTS Twenty-one studies screening 10,275 patients with dyspepsia were included. The pooled seroprevalence of CeD based on a positive anti-tissue transglutaminase antibody and/or anti-endomysial antibody was 4.8% (95% CI [2.8, 6.7%], I2 = 87.7%). The pooled biopsy-confirmed CeD prevalence was 1.5% (95% CI [1.0, 1.9%]; I2 = 59.8%) in these patients. Both seroprevalence (Odds ratio: 1.8; 95% CI [0.8, 4.0%]; I2 = 0%) and prevalence of biopsy-confirmed CeD (Odds ratio: 1.4; 95% CI [0.8, 2.4]; I2 = 0%) were not higher in patients with dyspepsia compared to controls. There was a moderate risk of selection bias and significant heterogeneity in the pooled results. CONCLUSIONS The pooled prevalence of CeD in patients with dyspepsia was 1.5% and it was not significantly higher than the general population. These results do not support screening of patients with dyspepsia for CeD.
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Affiliation(s)
- Achintya D Singh
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
| | - Samia Ellias
- Department of Gastrointestinal Surgery, Mayo Clinic, Rochester, MN, USA
| | - Prashant Singh
- Department of Gastroenterology, University of Michigan, Ann Arbor, MI, USA
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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18
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Biomarkers for the diagnosis and monitoring of celiac disease: can you count on me? Curr Opin Gastroenterol 2022; 38:263-269. [PMID: 35645020 DOI: 10.1097/mog.0000000000000825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
PURPOSE OF REVIEW Different markers are available to diagnose and monitor celiac disease (CeD); however, the concordance among them and their efficacy are still controversial. We aim at defining the efficacy of CeD biomarkers, their advantages and limits. RECENT FINDINGS CeD diagnostic criteria are widely accepted, being a positive serology and duodenal atrophy (according to the Marsh-Oberhuber score) the main hallmarks. Flow cytometry and other molecular biomarkers support the diagnosis of refractory CeD. On the other side, CeD monitoring is less defined, as the biomarkers are not always reliable. To date, the reference standard to detect mucosal healing is represented by duodenal histology, but its timing and significance are debated. Novel scores may better define the trend of mucosal damage and MicroRNAs are among the innovative noninvasive biomarkers. The assessment of a correct gluten-free diet (GFD) is another aspect of CeD monitoring, based upon questionnaires and recently developed tools such as dosage of urinary or faecal gluten immunogenic peptides. SUMMARY Clinicians lack of a widely acknowledged tools to monitor CeD and GFD. Here, we present the efficacy of the most used markers.
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Nazario E, Lasa J, Schill A, Duarte B, Berardi D, Paz S, Muryan A, Zubiaurre I. IgA Deficiency Is Not Systematically Ruled Out in Patients Undergoing Celiac Disease Testing. Dig Dis Sci 2022; 67:1238-1243. [PMID: 33770329 DOI: 10.1007/s10620-021-06939-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 03/06/2021] [Indexed: 01/12/2023]
Abstract
BACKGROUND Guidelines for celiac disease (CD) testing recommend total serum IgA determination alongside anti-transglutaminase IgA antibodies. It is not well known if lack of serum IgA determination is a common finding in clinical practice. AIM To determine the prevalence of lack of serum IgA determination among patients screened for celiac disease. MATERIALS AND METHODS We identified all subjects who underwent serum anti-transglutaminase IgA and/or other CD-related antibodies determination at a single teaching hospital in Buenos Aires from October 2019 to February 2020. Medical records were reviewed to select adult patients who were tested for celiac disease. The primary outcome was the proportion of patients with inadequate testing for celiac disease due to lack of serum IgA determination. We retrieved the following variables from each patient's record: age, gender, body mass index, symptoms present at screening, first-grade family history of CD, history of type-1 diabetes mellitus, autoimmune hypothyroidism, Down's syndrome. RESULTS Overall, 1122 patients were included for analysis. Lack of serum IgA determination prevalence was 20.49%. Among patients who did have serum IgA determination, the prevalence of IgA deficiency was 5.16%. The following variables were independently associated with a significantly increased odds of serum IgA determination: diarrhea [OR 1.55 (1.01-2.34)] and abdominal pain [OR 2.28 (1.44-3.63)]; higher body mass index [OR 0.91 (0.85-0.98)], osteoporosis [OR 0.49 (0.28-0.89)], hypothyroidism [OR 0.18 (0.07-0.45)], arthralgia/arthritis [OR 0.47 (0.27-0.85)], or testing by endocrinologist [OR 0.46 (0.23-0.91)] and gynecologist [OR 0.14 (0.06-0.31)] were inversely associated. CONCLUSION IgA deficiency is not systematically ruled out in a relatively high proportion of patients undergoing serological screening of celiac disease.
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Affiliation(s)
- Ezequiel Nazario
- Gastroenterology Department, Hospital Británico de Buenos Aires, Perdriel 74 (1012), Buenos Aires, Argentina
| | - Juan Lasa
- Gastroenterology Department, Hospital Británico de Buenos Aires, Perdriel 74 (1012), Buenos Aires, Argentina.
| | - Amalia Schill
- Biochemistry Department, Hospital Británico de Buenos Aires, Buenos Aires, Argentina
| | - Belen Duarte
- Gastroenterology Department, Hospital Británico de Buenos Aires, Perdriel 74 (1012), Buenos Aires, Argentina
| | - Diego Berardi
- Gastroenterology Department, Hospital Británico de Buenos Aires, Perdriel 74 (1012), Buenos Aires, Argentina
| | - Silvina Paz
- Gastroenterology Department, Hospital Británico de Buenos Aires, Perdriel 74 (1012), Buenos Aires, Argentina
| | - Alexis Muryan
- Biochemistry Department, Hospital Británico de Buenos Aires, Buenos Aires, Argentina
| | - Ignacio Zubiaurre
- Gastroenterology Department, Hospital Británico de Buenos Aires, Perdriel 74 (1012), Buenos Aires, Argentina
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Losurdo G, Di Leo M, Santamato E, Arena M, Rendina M, Luigiano C, Ierardi E, Di Leo A. Serologic diagnosis of celiac disease: May it be suitable for adults? World J Gastroenterol 2021; 27:7233-7239. [PMID: 34876785 PMCID: PMC8611199 DOI: 10.3748/wjg.v27.i42.7233] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/02/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
The diagnosis of coeliac disease (CD) in adult patients requires the simultaneous assessment of clinical presentation, serology, and typical histological picture of villous atrophy. However, several years ago, the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines approved new criteria for the diagnosis in children: Biopsy could be avoided when anti-transglutaminase antibody (TGA) values exceed the cut-off of × 10 upper limit of normal (ULN) and anti-endomysium antibodies are positive, independently from value. This "no biopsy" approach is a decisive need for pediatric population, allowing to avoid stressful endoscopic procedures in children, if unnecessary. This approach relies on the correlation existing in children between TGA levels and assessment of mucosal atrophy according to Marsh's classification. Several lines of evidence have shown that patients with villous atrophy have markedly elevated TGA levels. Therefore, we aim to perform a narrative review on the topic in adults. Despite that some studies confirmed that the × 10 ULN threshold value has a very good diagnostic performance, several lines of evidence in adults suggest that TGA cut off should be different from that of pediatric population for reaching a good correlation with histological picture. In conclusion, the heterogeneity of study reports as well as some conditions, which may hamper the serological diagnosis of CD (such as seronegative CD and non-celiac villous atrophy) and are much more common in adults than in children, could represent a limitation for the "no biopsy" approach to CD diagnosis in patients outside the pediatric age.
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Affiliation(s)
- Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Milena Di Leo
- Unit of Digestive Endoscopy, San Paolo Hospital, Milan 20090, Italy
| | - Edoardo Santamato
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Monica Arena
- Unit of Digestive Endoscopy, San Paolo Hospital, Milan 20090, Italy
| | - Maria Rendina
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Carmelo Luigiano
- Unit of Digestive Endoscopy, San Paolo Hospital, Milan 20090, Italy
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
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Large-Scale Screening in General Population Children for Celiac Disease with a Multiplex Electrochemiluminescence (ECL) Assay. J Immunol Res 2021; 2020:8897656. [PMID: 33426098 PMCID: PMC7775136 DOI: 10.1155/2020/8897656] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 12/15/2020] [Accepted: 12/17/2020] [Indexed: 11/17/2022] Open
Abstract
Background Autoimmunity Screening for Kids (ASK) study was launched to screen general population children for type 1 diabetes (T1D) and celiac disease (CD). Methods A total of 23,319 children from general population were screened. A high throughput multiplex electrochemiluminescence (ECL) assay to screen multiautoantibodies in a single well was applied, parallel with a standard radiobinding assay (RBA). All children with any positive autoantibodies in screening were revisited within one month for confirmation and followed every 6 months. Results Among 23,319 children, 2.6% (606/23,319) of children were tested positive for TGA. Multiplex ECL assay detected more TGA (584/23,319) in the initial screening than RBA (490/23,319, p = 0.004) and was able to detect TGA earlier than RBA in a subset of children by 0.8 to 34.8 months. Prevalence of TGA by either ECL or RBA in children with islet autoantibodies was found significantly higher than overall prevalence in general population screened. Conclusions A multiplex ECL assay was more sensitive than standard RBA by identifying more TGA positivity and detecting TGA earlier in general population screening. It also provides a high efficient tool with its unique advantage of multiplexing measurements to screen for multiple autoimmune diseases simultaneously in general population.
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Mass Screening for Celiac Disease: The Autoimmunity Screening for Kids Study. Am J Gastroenterol 2021; 116:180-187. [PMID: 32701732 PMCID: PMC7775339 DOI: 10.14309/ajg.0000000000000751] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 05/14/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The Autoimmunity Screening for Kids (ASK) study is a large scale pediatric screening study in Colorado for celiac disease (CD) and type 1 diabetes. This is a report of the CD outcomes for the first 9,973 children screened through ASK. METHODS ASK screens children aged 1-17 years for CD using 2 highly sensitive assays for tissue transglutaminase autoantibodies (TGA): a radiobinding (RBA) assay for IgA TGA and an electrochemiluminescence (ECL) assay that detects all TGA isotypes. Children who test positive on either assay are asked to return for confirmatory testing. Those with a confirmed RBA TGA level ≥ 0.1 (twice the upper limit of normal) are referred to the Colorado Center for Celiac Disease for further evaluation; all others are referred to primary care. RESULTS Of the initial 9,973 children screened, 242 children were TGA+ by any assay. Of those initially positive, 185 children (76.4%) have completed a confirmation blood draw with 149 children (80.5%) confirming positive by RBA TGA. Confirmed RBA TGA+ was associated with a family history of CD (odds ratio [OR] = 1.83; 95% confidence interval 1.06-3.16), non-Hispanic white ethnicity (OR = 3.34; 2.32-4.79), and female sex (OR = 1.43; 1.03-1.98). Gastrointestinal symptoms of CD, assessed at the initial screening, were reported equally often among the RBA TGA+ vs TGA- children (32.1% vs 30.5%, P = 0.65). DISCUSSION The initial results of this ongoing mass-screening program confirm a high prevalence of undiagnosed CD autoimmunity in a screened US population. Symptoms at initial screening were not associated with TGA status (see Visual abstract, Supplementary Digital Content 5, http://links.lww.com/AJG/B587).
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Lebwohl B, Rubio-Tapia A. Epidemiology, Presentation, and Diagnosis of Celiac Disease. Gastroenterology 2021; 160:63-75. [PMID: 32950520 DOI: 10.1053/j.gastro.2020.06.098] [Citation(s) in RCA: 196] [Impact Index Per Article: 49.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 04/22/2020] [Accepted: 06/06/2020] [Indexed: 12/16/2022]
Abstract
The incidence of celiac disease is increasing, partly because of improved recognition of, and testing for, the disease. The rise in incidence is also due to a real increase of this immune-based disorder, independent of disease detection. The reasons for this true rise in recent decades are unknown but may be related to environmental factors that may promote loss of tolerance to dietary gluten. Strategies to reduce the development of celiac disease have not been proven successful in randomized trials, but the quantity of early-life gluten exposure has been a major focus of prevention efforts. The criteria for the diagnosis of celiac disease are changing, but in adults, diagnosis still depends on the presence of duodenal villous atrophy while the patient is on a gluten-containing diet, along with findings from serology analysis. Although guidelines in the United States continue to mandate a biopsy at all ages, some children receive a diagnosis of celiac disease without a biopsy. If proven accurate and scalable, assays that detect gluten-HLA tetramer complexes might be used in diagnosis to be made in the context of a gluten-free diet without intestinal biopsy.
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Affiliation(s)
- Benjamin Lebwohl
- Department of Medicine, Columbia University Irving Medical Center, New York, New York; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
| | - Alberto Rubio-Tapia
- Department of Gastroenterology, Hepatology, and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
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Stahl MG, Dong F, Lamb MM, Waugh KC, Taki I, Størdal K, Stene LC, Rewers MJ, Liu E, Norris JM, Mårild K. Childhood growth prior to screen-detected celiac disease: prospective follow-up of an at-risk birth cohort. Scand J Gastroenterol 2020; 55:1284-1290. [PMID: 32941083 PMCID: PMC7646943 DOI: 10.1080/00365521.2020.1821087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 08/24/2020] [Accepted: 09/01/2020] [Indexed: 02/04/2023]
Abstract
OBJECTIVES To determine the association between childhood growth prior to the development of celiac disease (CD) and CD autoimmunity (CDA) identified by periodic serological screening. STUDY DESIGN The Diabetes Autoimmunity Study in the Young cohort includes 1979 genetically at-risk children from Denver, Colorado, with annual growth measurements from age nine months until ten years. Between 1993 and February 2019, 120 children developed CDA defined by persistent positive tissue transglutaminase autoantibodies (TGA); among these, 71 met our criteria for CD based on histopathological findings or high TGA levels. Age- and sex-specific z-scores of weight, body mass index (BMI), and height prior to seroconversion were derived using US reference charts as standards. Joint modeling of serial growth measurements was used to estimate adjusted hazard ratios (aHRs) accounting for celiac-associated human leukocyte antigens, early-life feeding practices, and socio-demographics. RESULTS In the first 10 years of life, there were no significant associations between the child's current weight, BMI and height and the risk of screening-detected CDA or CD, neither was the weight nor BMI velocity associated with CDA or CD as identified by screening (all aHRs approximated 1). Increased height velocity was associated with later CD, but not CDA, development (aHR per 0.01-z score/year, 1.28; 95% confidence interval [CI] 1.18-1.38 and 1.03; 0.97-1.09, respectively). CONCLUSIONS In the first 10 years of life, from prospectively collected serial growth measurements, we found no evidence of impaired childhood growth before CD and CDA development as identified through early and periodic screening.
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Affiliation(s)
- Marisa G. Stahl
- Digestive Health Institute, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Fran Dong
- Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Molly M. Lamb
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Kathleen C. Waugh
- Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Iman Taki
- Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Ketil Størdal
- Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway
- Department of Pediatrics, Østfold Hospital Trust, Grålum, Norway
| | - Lars C. Stene
- Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Marian J. Rewers
- Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Edwin Liu
- Digestive Health Institute, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Jill M. Norris
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Karl Mårild
- Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden
- Department of Pediatric Gastroenterology, Queen Silvia Children’s Hospital, Gothenburg, Sweden
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Singh P, Singh A, Silvester JA, Sachdeva V, Chen X, Xu H, Leffler DA, Ahuja V, Duerksen DR, Kelly CP, Makharia GK. Inter- and Intra-assay Variation in the Diagnostic Performance of Assays for Anti-tissue Transglutaminase in 2 Populations. Clin Gastroenterol Hepatol 2020; 18:2628-2630. [PMID: 31546060 PMCID: PMC7082178 DOI: 10.1016/j.cgh.2019.09.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Revised: 09/11/2019] [Accepted: 09/15/2019] [Indexed: 02/07/2023]
Abstract
Tissue transglutaminse-2 (TG2)-based immunoassays are the cornerstone of diagnosis in celiac disease (CeD), with a reported pooled sensitivity as high as 98%.1 However, a few small, single-center studies have questioned their sensitivity in clinical practice.2-5 Moreover, commercial kits use variable TG2 antigens,6 with cutoffs determined by using small, poorly defined populations. Variation in diagnostic performance of anti-TG2 assays in different racial and geographic populations has not yet been studied. We compared the interassay and intra-assay variations in diagnostic performance of 4 immunoglobulin (Ig)A-anti-TG2 assays in Canadian and Indian populations.
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Affiliation(s)
- Prashant Singh
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Alka Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Jocelyn A Silvester
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts
| | - Vikas Sachdeva
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Xinhua Chen
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Hua Xu
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Daniel A Leffler
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Takeda Pharmaceuticals Inc, Tokyo, Japan
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Donald R Duerksen
- Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
| | - Ciaran P Kelly
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
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Tiberti C, Montuori M, Trovato CM, Panimolle F, Filardi T, Valitutti F, Lenzi A, Cucchiara S, Morano S. Gluten-free diet impact on dynamics of pancreatic islet-specific autoimmunity detected at celiac disease diagnosis. Pediatr Diabetes 2020; 21:774-780. [PMID: 32418261 DOI: 10.1111/pedi.13054] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Revised: 04/29/2020] [Accepted: 05/06/2020] [Indexed: 01/12/2023] Open
Abstract
OBJECTIVE Almost 6% of celiac disease (CD) patients at diagnosis are positive for at least one of the main pancreatic islet autoantibodies that characterize type 1 diabetes (T1D). Few information, dated back to almost two decades ago, exist as to whether a gluten-free diet (GFD) could reduce the islet-specific autoimmunity detected in patients at CD diagnosis. Aim of the study was to evaluate the impact of GFD on 31 patients who presented islet-specific autoimmunity at CD diagnosis. METHODS CD patient sera collected at diagnosis and throughout the GFD were analyzed for the main humoral autoantibodies so far identified in T1D, directed against one or more among insulin, glutamic-acid decarboxylase, tyrosine-phosphatase 2, and zinc cation-efflux transporter autoantigens. RESULTS GFD (median duration 39 months) was associated to a decrease or disappearance of the islet-specific autoantibodies in 71% of CD patients. Almost 80% of the patients who became autoantibody-negative during the GFD were positive for only one of the islet-specific autoimmune markers at CD diagnosis, with none of them developing diabetes. Conversely, 80% of the CD patients positive at diagnosis for ≥2 islet-specific autoantibodies were still positive after more than two years of GFD, with 25% of them developing T1D. CONCLUSIONS Various factors appear to influence, individually or in combination, the effects of the GFD on pancreatic islet-specific autoimmune response detected at CD diagnosis. These factors include the number of diabetes autoantibodies found at CD diagnosis, the adherence to the GFD, its duration and an asymptomatic clinical presentation of CD.
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Affiliation(s)
- Claudio Tiberti
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Monica Montuori
- Department of Pediatrics, Pediatric Gastroenterology, and Liver Unit, Sapienza University of Rome, Rome, Italy
| | - Chiara Maria Trovato
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.,Department of Pediatrics, Pediatric Gastroenterology, and Liver Unit, Sapienza University of Rome, Rome, Italy
| | - Francesca Panimolle
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Tiziana Filardi
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Francesco Valitutti
- Department of Pediatrics, Pediatric Gastroenterology, and Liver Unit, Sapienza University of Rome, Rome, Italy
| | - Andrea Lenzi
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Salvatore Cucchiara
- Department of Pediatrics, Pediatric Gastroenterology, and Liver Unit, Sapienza University of Rome, Rome, Italy
| | - Susanna Morano
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
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Tiberti C, Panimolle F, Borghini R, Montuori M, Trovato CM, Filardi T, Lenzi A, Picarelli A. Type 1 diabetes, thyroid, gastric and adrenal humoral autoantibodies are present altogether in almost one third of adult celiac patients at diagnosis, with a higher frequency than children and adolescent celiac patients. Scand J Gastroenterol 2020; 55:549-554. [PMID: 32393142 DOI: 10.1080/00365521.2020.1754898] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background: No data are available on the frequency of organ-specific humoral autoimmunity at diagnosis of adult celiac disease (CD).Aim: To evaluate the humoral immunoreactivities specific of type 1 diabetes (T1D), thyroid (THD), atrophic-gastritis (AG) and Addison's (AD) diseases in 92 adult CD patients at diagnosis and 237 adult healthy subjects (CTRL).Methods: T1D, THD and AD specific autoantibodies were analyzed by radioimmunoprecipitation assays. AG autoantibodies were detected by enzyme-linked immunosorbent assay.Results: Of 92 CD patients, 31.5% were positive for at least one of the organ-specific autoantibodies investigated (p < .0001 vs CTRL). Thyroid, diabetes, gastric and adrenal-autoantibodies, that increase with age at diagnosis, were detected in 12.0%, 10.9%, 10.9%, 2.2% of CD patients, respectively. Gastric- and diabetes- rather than thyroid- and adrenal-autoimmunity seem to be specifically related to presence of CD.Conclusions: One third of adult CD patients at diagnosis is target of at least one organ-specific autoantibody. A systematic organ-specific autoantibody screening in these patients might be of value to promptly identify, prevent or treat the relative diseases.
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Affiliation(s)
- Claudio Tiberti
- Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Francesca Panimolle
- Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Raffaele Borghini
- Department of Internal Medicine and Clinical Specialties, "Sapienza" University of Rome, Rome, Italy
| | - Monica Montuori
- Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, "Sapienza" University of Rome, Rome, Italy
| | - Chiara Maria Trovato
- Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, "Sapienza" University of Rome, Rome, Italy
| | - Tiziana Filardi
- Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Andrea Lenzi
- Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Antonio Picarelli
- Department of Internal Medicine and Clinical Specialties, "Sapienza" University of Rome, Rome, Italy
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Petrarca L, Pontone S, Nenna R. Celiac Disease Screening in Infertile Women: Is It Worth It? JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2020; 41:281-282. [PMID: 30784566 DOI: 10.1016/j.jogc.2018.09.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Indexed: 11/29/2022]
Affiliation(s)
- Laura Petrarca
- Department of Pediatrics, Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy
| | - Stefano Pontone
- Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy
| | - Raffaella Nenna
- Department of Pediatrics, Sapienza University of Rome, Rome, Italy
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29
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Damoiseaux M, van Doorn W, van Lochem E, Damoiseaux J. Testing for IgA anti-tissue transglutaminase in routine clinical practice: Requesting behaviour in relation to prevalence of positive results. J Transl Autoimmun 2020; 3:100045. [PMID: 32743526 PMCID: PMC7388373 DOI: 10.1016/j.jtauto.2020.100045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 03/07/2020] [Indexed: 01/28/2023] Open
Abstract
OBJECTIVE Due to the high awareness of coeliac disease and improvement of serological tests, the number of requested laboratory tests has increased substantially over the years. In the current study we have evaluated the requesting behaviour of distinct clinical disciplines in relation to the prevalence of positive results and in the context of existing guidelines. METHODS Data were retrospectively extracted from the laboratory information system over a time-span of 5 years in a tertiary hospital and compared with the situation in a secondary hospital. RESULTS Data reveal that for initial testing (n=18,183) the percentage positive results for IgA anti-TTG is <2%. Paediatricians have a slightly higher percentage of seropositive results (2.4-4.0%). Early confirmation (<2 months) of positive results by IgA anti-endomysium antibodies in an independent sample is only performed in a minority of paediatric patients. The majority of positive patients, however, have follow-up measurements (<14 months) in order to examine compliance to a gluten-free diet. Interestingly, initial requests for paediatric patients reveal an equal distribution between boys and girls, while in adult patients there is a two times preponderance of requests in female patients, similar to the female/male ratio in patients with positive results, being either paediatric or adult patients. CONCLUSION Although laboratory testing for coeliac disease may be primarily used to exclude the disease, it is evident that the percentage positive results for IgA anti-TTG is extremely low. This may indicate that the clinical manifestations that warrant testing, should be further specified in order to increase the pre-test probability. As the specific serology is important to bypass a biopsy in the diagnosis of coeliac disease according to the paediatric guideline, the confirmation in an independent sample needs to get more attention.
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Affiliation(s)
- Maurits Damoiseaux
- Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands
| | - William van Doorn
- Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Ellen van Lochem
- Department of Microbiology and Immunology, Rijnstate Hospital, Arnhem, the Netherlands
| | - Jan Damoiseaux
- Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands
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Oxentenko AS, Rubio-Tapia A. Celiac Disease. Mayo Clin Proc 2019; 94:2556-2571. [PMID: 31806106 DOI: 10.1016/j.mayocp.2019.02.019] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 02/08/2019] [Accepted: 02/14/2019] [Indexed: 12/16/2022]
Abstract
Celiac disease (CD) affects approximately 1% of the general population, although most cases remain unrecognized. Because CD is a multisystem disorder with protean clinical manifestations, a high index of suspicion is needed to make an appropriate diagnosis. A diagnosis of CD is made in a patient who is genetically predisposed based on the presence of compatible clinical features, positive highly specific celiac serologic findings, duodenal biopsies that document enteropathy, and improvement with a gluten-free diet. The differential diagnoses for the clinical features and the histologic findings seen in patients with CD are numerous and need to be considered; because the management of celiac disease consists of a lifelong gluten-free diet, ensuring that the diagnosis is correctly established is of utmost importance. The aim of this review is to provide practicing clinicians with the most current information on the diagnosis and management of CD, including new developments and the approach to controversial issues.
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Affiliation(s)
- Amy S Oxentenko
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN.
| | - Alberto Rubio-Tapia
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
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Håkansson Å, Andrén Aronsson C, Brundin C, Oscarsson E, Molin G, Agardh D. Effects of Lactobacillus plantarum and Lactobacillus paracasei on the Peripheral Immune Response in Children with Celiac Disease Autoimmunity: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients 2019; 11:1925. [PMID: 31426299 PMCID: PMC6723580 DOI: 10.3390/nu11081925 10.3390/nu11081925] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Two Lactobacillus strains have proven anti-inflammatory properties by reducing pro-inflammatory responses to antigens. This randomized double-blind placebo-controlled trial tested the hypothesis that L. plantarum HEAL9 and L. paracasei 8700:2 suppress ongoing celiac disease autoimmunity in genetically at risk children on a gluten-containing diet in a longitudinally screening study for celiac disease. Seventy-eight children with celiac disease autoimmunity participated of whom 40 received 1010 CFU/day of L. plantarum HEAL9 and L. paracasei 8700:2 (probiotic group) and 38 children maltodextrin (placebo group) for six months. Blood samples were drawn at zero, three and six months and phenotyping of peripheral blood lymphocytes and IgA and IgG autoantibodies against tissue transglutaminase (tTG) were measured. In the placebo group, naïve CD45RA+ Th cells decreased (p = 0.002) whereas effector and memory CD45RO+ Th cells increased (p = 0.003). In contrast, populations of cells expressing CD4+CD25highCD45RO+CCR4+ increased in the placebo group (p = 0.001). Changes between the groups were observed for NK cells (p = 0.038) and NKT cells (p = 0.008). Median levels of IgA-tTG decreased more significantly over time in the probiotic (p = 0.013) than in the placebo (p = 0.043) group whereas the opposite was true for IgG-tTG (p = 0.062 respective p = 0.008). In conclusion, daily oral administration of L. plantarum HEAL9 and L. paracasei 8700:2 modulate the peripheral immune response in children with celiac disease autoimmunity.
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Affiliation(s)
- Åsa Håkansson
- Department of Food Technology Engineering and Nutrition, Lund University, Box 124, 22100 Lund, Sweden
| | - Carin Andrén Aronsson
- The Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, 21428 Malmö, Sweden
| | - Charlotte Brundin
- The Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, 21428 Malmö, Sweden
| | - Elin Oscarsson
- The Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, 21428 Malmö, Sweden
| | - Göran Molin
- Department of Food Technology Engineering and Nutrition, Lund University, Box 124, 22100 Lund, Sweden
| | - Daniel Agardh
- The Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, 21428 Malmö, Sweden.
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Effects of Lactobacillus plantarum and Lactobacillus paracasei on the Peripheral Immune Response in Children with Celiac Disease Autoimmunity: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients 2019; 11:nu11081925. [PMID: 31426299 PMCID: PMC6723580 DOI: 10.3390/nu11081925] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 07/29/2019] [Accepted: 08/13/2019] [Indexed: 01/01/2023] Open
Abstract
Two Lactobacillus strains have proven anti-inflammatory properties by reducing pro-inflammatory responses to antigens. This randomized double-blind placebo-controlled trial tested the hypothesis that L. plantarum HEAL9 and L. paracasei 8700:2 suppress ongoing celiac disease autoimmunity in genetically at risk children on a gluten-containing diet in a longitudinally screening study for celiac disease. Seventy-eight children with celiac disease autoimmunity participated of whom 40 received 1010 CFU/day of L. plantarum HEAL9 and L. paracasei 8700:2 (probiotic group) and 38 children maltodextrin (placebo group) for six months. Blood samples were drawn at zero, three and six months and phenotyping of peripheral blood lymphocytes and IgA and IgG autoantibodies against tissue transglutaminase (tTG) were measured. In the placebo group, naïve CD45RA+ Th cells decreased (p = 0.002) whereas effector and memory CD45RO+ Th cells increased (p = 0.003). In contrast, populations of cells expressing CD4+CD25highCD45RO+CCR4+ increased in the placebo group (p = 0.001). Changes between the groups were observed for NK cells (p = 0.038) and NKT cells (p = 0.008). Median levels of IgA-tTG decreased more significantly over time in the probiotic (p = 0.013) than in the placebo (p = 0.043) group whereas the opposite was true for IgG-tTG (p = 0.062 respective p = 0.008). In conclusion, daily oral administration of L. plantarum HEAL9 and L. paracasei 8700:2 modulate the peripheral immune response in children with celiac disease autoimmunity.
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Abstract
OBJECTIVES To determine the association between the amount of gluten intake in childhood and later celiac disease (CD), for which data are currently scarce. METHODS The prospective Diabetes Autoimmunity Study in the Young cohort includes 1875 at-risk children with annual estimates of gluten intake (grams/d) from age 1 year. From 1993 through January 2017, 161 children, using repeated tissue transglutaminase (tTGA) screening, were identified with CD autoimmunity (CDA) and persistent tTGA positivity; of these children, 85 fulfilled CD criteria of biopsy-verified histopathology or persistently high tTGA levels. Cox regression, modeling gluten intake between ages 1 and 2 years (i.e., in 1-year-olds), and joint modeling of cumulative gluten intake throughout childhood were used to estimate hazard ratios adjusted for confounders (aHR). RESULTS Children in the highest third of gluten intake between the ages of 1 and 2 years had a 2-fold greater hazard of CDA (aHR 2.17; 95% confidence interval [CI], 1.22-3.88; P value = 0.01) and CD (aHR 1.96; 95% CI, 0.90-4.24; P value = 0.09) than those in the lowest third. The risk of developing CDA increased by 5% per daily gram increase in gluten intake (aHR 1.05; 95% CI, 1.00-1.09; P value = 0.04) in 1-year-olds. The association between gluten intake in 1-year-olds and later CDA or CD did not differ by the child's human leukocyte antigen genotype. The incidence of CD increased with increased cumulative gluten intake throughout childhood (e.g., aHR 1.15 per SD increase in cumulative gluten intake at age 6; 95% CI, 1.00-1.32; P value = 0.04). DISCUSSION Gluten intake in 1-year-olds is associated with the future onset of CDA and CD in children at risk for the disease.
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Faye AS, Lebwohl B. Celiac Disease: Diagnosis, Screening, and Prognosis. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 4E 2019:139-149. [DOI: 10.1002/9781119211419.ch9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Paruk IM, Naidoo VG, Pirie FJ, Maharaj S, Nkwanyana NM, Dinnematin HL, Ganie Y, Ramdial PK, Motala AA. Prevalence and characteristics of celiac disease in South African patients with type 1 diabetes mellitus: Results from the Durban Diabetes and Celiac Disease Study. J Gastroenterol Hepatol 2019; 34:673-678. [PMID: 30600564 DOI: 10.1111/jgh.14596] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 12/20/2018] [Accepted: 12/25/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM The aim of this study was to assess the prevalence and characteristics of celiac disease (CD) in all patients with type 1 diabetes mellitus attending a tertiary adult diabetes clinic in Durban, South Africa. METHODS This was a cross-sectional observational study that screened 202 patients; of these, 56.4% were African (Black), 31.7% Asian Indian, 4.5% White, and 7.4% mixed race. Demographic data, symptoms, and anthropometry were documented. Blood tests included anti-tissue transglutaminase antibody (tTG), anti-endomysial antibody (EMA), and anti-gliadin antibody (AGA). Endoscopy and duodenal biopsy were performed in patients with celiac antibodies. Diagnosis of CD was based on the modified Marsh classification. RESULTS Mean age and mean duration of diabetes were 26.4 ± 11.4 and 10.7 ± 9.1 years, respectively. Celiac antibodies were found in 65 (32.2%) patients: EMA 7.4%, tTG immunoglobulin A (IgA) 8.4%, tTG immunoglobulin G 1.9%, AGA IgA 18.3%, and AGA immunoglobulin G 21.8%. Histological evidence of CD was found in 5.9% (n = 12/202): 2.5% were classed as definite CD (Marsh 3) and 3.4% as potential CD (Marsh 1). None of the patients with CD were symptomatic. The sensitivity of AGA IgA, EMA, and tTG IgA antibodies for detecting histologically proven CD was 66.7%, 50.0%, and 41.7%, respectively. CONCLUSION The prevalence of CD was similar to reports from western countries. No ethnic specific differences were noted. CD was silent in all patients in this study. The sensitivity of EMA and tTG antibodies was poor and merits further evaluation as screening tools for CD in South African patients with type 1 diabetes mellitus.
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Affiliation(s)
- Imran M Paruk
- Department of Diabetes and Endocrinology, University of KwaZulu-Natal, Durban, South Africa
| | - Vasudevan G Naidoo
- Department of Gastroenterology and Hepatology, University of KwaZulu-Natal, Durban, South Africa
| | - Fraser J Pirie
- Department of Diabetes and Endocrinology, University of KwaZulu-Natal, Durban, South Africa
| | - Sureka Maharaj
- Department of Diabetes and Endocrinology, University of KwaZulu-Natal, Durban, South Africa
| | | | - Hilary L Dinnematin
- Department of Haematology, Inkosi Albert Luthuli Central Hospital, Durban, South Africa
| | - Yasmeen Ganie
- Department of Paediatrics, Inkosi Albert Luthuli Central Hospital, Durban, South Africa
| | - Pratistadevi K Ramdial
- Department of Anatomical Pathology, Inkosi Albert Luthuli Central Hospital, Durban, South Africa
| | - Ayesha A Motala
- Department of Diabetes and Endocrinology, University of KwaZulu-Natal, Durban, South Africa
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Prevalence of Celiac Disease in a Long-term Study of a Spanish At-genetic-risk Cohort From the General Population. J Pediatr Gastroenterol Nutr 2019; 68:364-370. [PMID: 30418411 DOI: 10.1097/mpg.0000000000002195] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
OBJECTIVES To perform long-term celiac disease (CD) screening in an HLA-DQ2 (+) cohort from the general population and to assess the influence of risk genotypes on its development. METHODS In 2004, an HLA-DQ2 (+) cohort was selected. After the first CD screening at age 2 to 3 years, we performed a follow-up screening 8 to 10 years later. Antitransglutaminase 2 antibodies were determined using a rapid test kit. Results were confirmed by serum IgA antitransglutaminase 2 and IgA endomysial antibody determination. CD diagnosis was carried out by intestinal biopsies. Four HLA-DQ2 genotypic groups were used: G1: DQ2.5/DQ2.5 (G1A) or DQ2.5/ DQ2.2 (G1B); G2: DQ2.2/DQ7.5 (DQ2.5 trans); G3: DQ2.5/ X; G4: DQ2.2/X. RESULTS CD prevalence after 10 years of follow-up was 5.8% (95% confidence interval 3.8-8.7). One of every 3 HLA-DQ2(+) children carried at least 1 haplotype DQ2.2 or DQ7. The homozygous genotype DQ2.5/DQ2.5 and the HLA-DQ2.5 trans genotype increased CD risk 4- and 3-fold, respectively. The homozygous genotype DQ2.5/ DQ2.2 did not increase the CD risk. Children carrying G1 or G2 genotypes were diagnosed with CD earlier and more frequently during the follow-up compare with those carrying G3 or G4 genotypes. Approximately 81% of children with spontaneous antibody negativization after the first screening maintained negative antibodies. CONCLUSIONS A repeated screening of at-risk children during their follow-up allowed us to diagnose new CD cases. In our cohort, HLA- DQ2.5 trans genotype conferred a higher risk in the development of CD than HLA- DQ2.5/DQ2.2. The majority of children with potential CD and CD autoimmunity at 10 years of age remained healthy.
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Zhao Z, Gu Y, Miao D, Hoffmeyer E, Liu Y, Yu L. Determination of Autoantibodies to Transglutaminase by Electrochemiluminescence (ECL) Assay. Methods Mol Biol 2019; 1901:197-203. [PMID: 30539579 DOI: 10.1007/978-1-4939-8949-2_16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Appearance of autoantibodies to tissue transglutaminase (TGA) is the most reliable biomarker to identify celiac disease autoimmunity. A nonradioactive assay of determination of TGA was newly developed using electrochemiluminescence (ECL) technology. This ECL assay has been demonstrated to be more sensitive than current standard radio-binding assay (RBA) in detecting TGA and can detect TGA earlier among high-risk young children followed from birth.
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Affiliation(s)
- Zhiyuan Zhao
- Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA
- Department of Endocrinology, The Second Hospital of Jilin University, Jilin, China
| | - Yong Gu
- Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA
- Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Dongmei Miao
- Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA
| | - Eric Hoffmeyer
- Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA
| | - Yu Liu
- Department of Endocrinology, The Second Hospital of Jilin University, Jilin, China
| | - Liping Yu
- Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA.
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Rodrigo L, Pérez-Martinez I, Lauret-Braña E, Suárez-González A. Descriptive Study of the Different Tools Used to Evaluate the Adherence to a Gluten-Free Diet in Celiac Disease Patients. Nutrients 2018; 10:1777. [PMID: 30453479 PMCID: PMC6267102 DOI: 10.3390/nu10111777] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 11/07/2018] [Accepted: 11/14/2018] [Indexed: 12/12/2022] Open
Abstract
Celiac disease (CD) is a genetically conditioned autoimmune process that appears in susceptible people. It can affect people of any age, and slightly predominates in females. It has a fairly homogenous global distribution, with an average prevalence of 1⁻2%, the frequency having increased in recent decades. The only effective treatment is a strict and permanent gluten-free diet (GFD), although the level of compliance is poor, at about 50% of cases. To monitor the effectiveness of the GFD, several procedures involving various approaches are employed: (a) Periodic visits by expert Nutritionists; (b) Clinical follow-up; (c) Serological time controls of specific antibodies; (d) Serial endoscopies with collection of duodenal biopsies; (e) Use of structured questionnaires; and (f) Determination of gluten peptides derived from gluten in faeces and/or urine. All of these procedures are useful when applied, alone or in combination, depending on the cases. Some patients will only need to consult to their doctors, while others will require a multidisciplinary approach to assess their compliance with the GFD. In children, normalization of duodenal mucosa was achieved in 95% of cases within two years, while it is more delayed in adults, whose mucosa take longer time (3⁻5 years) to heal completely.
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Affiliation(s)
- Luis Rodrigo
- Gastroenterology Unit, Hospital Universitario Central de Asturias (HUCA), CSIC, Avda. de Roma s/n, 33011 Oviedo, Spain.
| | - Isabel Pérez-Martinez
- Gastroenterology Unit, Hospital Universitario Central de Asturias (HUCA), CSIC, Avda. de Roma s/n, 33011 Oviedo, Spain.
| | - Eugenia Lauret-Braña
- Gastroenterology Unit, Hospital Universitario Central de Asturias (HUCA), CSIC, Avda. de Roma s/n, 33011 Oviedo, Spain.
| | - Adolfo Suárez-González
- Gastroenterology Unit, Hospital Universitario Central de Asturias (HUCA), CSIC, Avda. de Roma s/n, 33011 Oviedo, Spain.
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Abstract
Standardization and harmonization are complementary tools to achieve higher testing quality in laboratory medicine. Both are of great relevance and are strongly needed in autoimmune diagnostics, due to the impressive advance in basic research and technological development observed in this diagnostic field in recent years that has led to the introduction of many new tests and new analytical methods. It is, therefore, essential that this strong innovative thrust is translated into clinical practice in a coordinated way to avoid confusion and the risk of potentially harmful errors for the patient. However, while standardization of antibody assays is a very complex task, harmonization of procedures and behaviors is a more feasible target and should necessarily include all the phases of the total testing process-in the pre-analytical phase, appropriateness of test requests, harmonization of autoantibody terminology, and adoption of uniform nomenclature for laboratory tests; in the analytical phase, harmonization of measurements, and sharing of test profiles and diagnostic algorithms; and in the post-analytical phase, harmonization of data reporting, and criteria for interpreting immunoserological results, especially harmonization of units, reference intervals, decision limits, and definition and notification of critical values. We here provide and discuss some examples of harmonization initiatives related to anti-nuclear antibodies, TSH receptor, and anti-thyroid peroxidase antibodies and to antibodies associated with autoimmune hepatitis and with celiac disease. These initiatives could be the starting steps to achieve a wider consensus and a closer interaction among stakeholders in the path of autoimmune diagnostics harmonization to enhance clinical effectiveness and provide greater patient safety.
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Parkkola A, Härkönen T, Ryhänen SJ, Uibo R, Ilonen J, Knip M. Transglutaminase antibodies and celiac disease in children with type 1 diabetes and in their family members. Pediatr Diabetes 2018; 19:305-313. [PMID: 28745034 DOI: 10.1111/pedi.12563] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 06/19/2017] [Accepted: 06/23/2017] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVES We set out to determine the prevalence of tissue transglutaminase antibodies (anti-tTG) and celiac disease (CD) in children with newly diagnosed type 1 diabetes (T1D) and their first-degree relatives (FDR). The hypothesis was that the individuals with both diabetes and CD form a distinct subgroup in terms of human leukocyte antigen (HLA) class II genetics, islet autoantibodies, and clinical characteristics at diabetes diagnosis. SUBJECTS AND METHODS This population-based observational study included 745 index children with T1D and their 2692 FDR from the Finnish Pediatric Diabetes Register. CD was ascertained by registers, patient records, and screening anti-tTG positive individuals for further testing. RESULTS Among the index children, 4.8% had anti-tTG at diabetes diagnosis, and at the end of the study 3.2% had CD. Among the relatives, 2.9% had anti-tTG (4.8% mothers, 2.4% fathers, and 2.1% siblings), and 2.5% had CD (4.6% mothers, 2.1% fathers, and 1.4% siblings). Anti-tTG and CD associated with the HLA DR3-DQ2 haplotype. The usual female predominance of CD patients was observed in relatives (70%) but not among index children (46%). The index children with both diseases had a lower number of detectable islet autoantibodies than those with diabetes alone. CONCLUSIONS The children with double diagnosis differed from those with diabetes alone in HLA genetics, humoral islet autoimmunity directed against fewer antigens, and in the lack of usual female preponderance among CD patients. Compared with 61% of the anti-tTG positive relatives, only 36% of anti-tTG positive index children developed CD implicating transient anti-tTG positivity at diagnosis of T1D.
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Affiliation(s)
- Anna Parkkola
- Scientific Laboratory, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Folkhälsan Research Center, Helsinki, Finland.,Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland
| | - Taina Härkönen
- Scientific Laboratory, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland
| | - Samppa J Ryhänen
- Scientific Laboratory, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland
| | - Raivo Uibo
- Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
| | - Jorma Ilonen
- Immunogenetics Laboratory, University of Turku, Turku, Finland
| | - Mikael Knip
- Scientific Laboratory, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Folkhälsan Research Center, Helsinki, Finland.,Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.,Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
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Novikova VP, Shapovalova NS. Point-of-care testing for celiac disease. DOKAZATEL'NAYA GASTROENTEROLOGIYA 2018; 7:40. [DOI: 10.17116/dokgastro2018703140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Hyytinen M, Savilahti E, Virtanen SM, Härkönen T, Ilonen J, Luopajärvi K, Uibo R, Vaarala O, Åkerblom HK, Knip M, Eskola V, Haavisto H, Hämäläinen AM, Holm C C, Järvenpää AL, Jokisalo R, Käär ML, Kaski U, Komulainen J, Korpela P, Lautala P, Niemi K, Nuuja A, Rantanen P, Renko R, Renlund M, Salo M, Talvitie T, Uotila T, Wetterstrand G, Hyöty H, Ilonen J, Klemetti P, Knip M, Kulmala P, Paronen J, Reunanen A, Saukkonen T, Savilahti E, Savola K, Teramo K, Vaarala O, Virtanen S. Avoidance of Cow's Milk-Based Formula for At-Risk Infants Does Not Reduce Development of Celiac Disease: A Randomized Controlled Trial. Gastroenterology 2017; 153:961-970.e3. [PMID: 28687275 DOI: 10.1053/j.gastro.2017.06.049] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Revised: 06/23/2017] [Accepted: 06/27/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Feeding during the first months of life might affect risk for celiac disease. Individuals with celiac disease or type 1 diabetes have been reported to have high titers of antibodies against cow's milk proteins. Avoidance of cow's milk-based formula for infants with genetic susceptibility for type 1 diabetes reduced the cumulative incidence of diabetes-associated autoantibodies. We performed a randomized controlled trial in the same population to study whether weaning to an extensively hydrolyzed formula reduced the risk of celiac disease autoimmunity or celiac disease. METHODS We performed a double-blind controlled trial of 230 infants with HLA-defined predisposition to type 1 diabetes and at least 1 family member with type 1 diabetes. The infants were randomly assigned to groups fed a casein hydrolysate formula (n = 113) or a conventional formula (control, n = 117) whenever breast milk was not available during the first 6-8 months of life. Serum samples were collected over a median time period of 10 years and analyzed for antibodies to tissue transglutaminase (anti-TG2A) using a radiobinding assay, to endomysium using an immunofluorescence assay, and antibodies to a deamidated gliadine peptide using an immunofluorometry assay. Duodenal biopsies were collected if levels of anti-TG2A exceeded 20 relative units. Cow's milk antibodies were measured during the first 2 years of life. RESULTS Of the 189 participants analyzed for anti-TG2A, 25 (13.2%) tested positive. Of the 230 study participants observed, 10 (4.3%) were diagnosed with celiac disease. We did not find any significant differences at the cumulative incidence of anti-TG2A positivity (hazard ratio, 1.14; 95% confidence interval, 0.51-2.54) or celiac disease (hazard ratio, 4.13; 95% confidence interval, 0.81-21.02) between the casein hydrolysate and cow's milk groups. Children who developed celiac disease had increased titers of cow's milk antibodies before the appearance of anti-TG2A or celiac disease. CONCLUSIONS In a randomized controlled trial of 230 infants with genetic risk factors for celiac disease, we did not find evidence that weaning to a diet of extensively hydrolyzed formula compared with cow's milk-based formula would decrease the risk for celiac disease later in life. Increased titers of cow's milk antibody before anti-TG2A and celiac disease indicates that subjects with celiac disease might have increased intestinal permeability in early life. ClinicalTrials.gov Number: NCT00570102.
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Affiliation(s)
- Mila Hyytinen
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland
| | - Erkki Savilahti
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Suvi M Virtanen
- Nutrition Unit, National Institute for Health and Welfare, Helsinki, Finland; University of Tampere, School of Health Sciences, Tampere, Finland; Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland; The Science Center of Pirkanmaa Hospital District, Tampere, Finland
| | - Taina Härkönen
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland
| | - Jorma Ilonen
- Immunogenetics Laboratory, University of Turku and Turku University Hospital, Turku, Finland
| | - Kristiina Luopajärvi
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Raivo Uibo
- Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
| | - Outi Vaarala
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Respiratory, Inflammation and Autoimmunity, Innovative Medicine, AstraZeneca, Molndal, Sweden
| | - Hans K Åkerblom
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Mikael Knip
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland; Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland.
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Werkstetter KJ, Korponay-Szabó IR, Popp A, Villanacci V, Salemme M, Heilig G, Lillevang ST, Mearin ML, Ribes-Koninckx C, Thomas A, Troncone R, Filipiak B, Mäki M, Gyimesi J, Najafi M, Dolinšek J, Dydensborg Sander S, Auricchio R, Papadopoulou A, Vécsei A, Szitanyi P, Donat E, Nenna R, Alliet P, Penagini F, Garnier-Lengliné H, Castillejo G, Kurppa K, Shamir R, Hauer AC, Smets F, Corujeira S, van Winckel M, Buderus S, Chong S, Husby S, Koletzko S. Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice. Gastroenterology 2017. [PMID: 28624578 DOI: 10.1053/j.gastro.2017.06.002] [Citation(s) in RCA: 195] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. METHODS We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified. RESULTS Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61-99.99); the PPV was 100.00 (95% CI, 98.68-100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67-99.96) to 100.00 (95% CI, 99.23-100.00). CONCLUSIONS Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555.
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Affiliation(s)
- Katharina Julia Werkstetter
- Dr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital, LMU Munich, Munich, Germany
| | - Ilma Rita Korponay-Szabó
- Celiac Disease Center Heim Pál Children's Hospital, Budapest and Department of Pediatrics, University of Debrecen, Debrecen, Hungary; Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
| | - Alina Popp
- Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland; University of Medicine and Pharmacy "Carol Davila" and National Institute for Mother and Child Health "Alessandrescu-Rusescu," Bucharest, Romania
| | | | | | - Gabriele Heilig
- Dr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital, LMU Munich, Munich, Germany
| | | | - Maria Luisa Mearin
- Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands
| | - Carmen Ribes-Koninckx
- Department of Pediatric Gastroenterology and Hepatology, La Fe University Hospital, Valencia, Spain
| | - Adrian Thomas
- Department of Pediatric Gastroenterology, Royal Manchester Children's Hospital, Manchester, United Kingdom
| | - Riccardo Troncone
- Department of Translational Medical Sciences & European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy
| | - Birgit Filipiak
- Dr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital, LMU Munich, Munich, Germany
| | - Markku Mäki
- Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
| | - Judit Gyimesi
- Celiac Disease Center Heim Pál Children's Hospital, Budapest and Department of Pediatrics, University of Debrecen, Debrecen, Hungary
| | - Mehri Najafi
- Department of Pediatric Gastroenterology & Hepatology, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Jernej Dolinšek
- Department of Pediatrics, University Medical Center (UMC), Maribor, Slovenia
| | | | - Renata Auricchio
- Department of Translational Medical Sciences & European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy
| | - Alexandra Papadopoulou
- Division of Gastroenterology, Hepatology and Nutrition, First Department of Pediatrics, Children's Hospitals "Agia Sophia," University of Athens, Athens, Greece
| | - Andreas Vécsei
- Gastroenterology Outpatient Clinic, St. Anna Children's Hospital, Medical University Vienna, Vienna, Austria
| | - Peter Szitanyi
- Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine and General Teaching Hospital, Charles University, Prague, Czech Republic
| | - Ester Donat
- Department of Pediatric Gastroenterology and Hepatology, La Fe University Hospital, Valencia, Spain
| | - Rafaella Nenna
- Department of Pediatrics, Sapienza University of Rome, Rome, Italy
| | | | - Francesca Penagini
- Department of Pediatric Gastroenterology, Addenbrookes Hospital, Cambridge, United Kingdom
| | - Hélène Garnier-Lengliné
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hôpital Necker-Enfants Malades, Paris, France
| | - Gemma Castillejo
- Department of Pediatric Gastroenterology and Nutrition, Hospital Universitari Sant Joan, Reus, Spain
| | - Kalle Kurppa
- Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
| | - Raanan Shamir
- Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Françoise Smets
- Université Catholique de Louvain, IREC, PEDI, Cliniques universitaires Saint Luc, Brussels, Belgium
| | - Susana Corujeira
- Department of Pediatric Gastroenterology, Hospital S. João, Porto, Portugal
| | - Myriam van Winckel
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Ghent University Hospital, Ghent, Belgium
| | - Stefan Buderus
- Department of Pediatrics, St. Marien Hospital, Bonn, Germany
| | - Sonny Chong
- Queen Mary's Hospital for Children, Carshalton, United Kingdom
| | - Steffen Husby
- Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark
| | - Sibylle Koletzko
- Dr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital, LMU Munich, Munich, Germany.
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Spencer M, Lenhart A, Baker J, Dickens J, Weissman A, Read AJ, Saini S, Saini SD. Primary care physicians are under-testing for celiac disease in patients with iron deficiency anemia: Results of a national survey. PLoS One 2017; 12:e0184754. [PMID: 28931034 PMCID: PMC5607174 DOI: 10.1371/journal.pone.0184754] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Accepted: 08/30/2017] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Iron deficiency anemia (IDA) is a common extra-intestinal manifestation of celiac disease (CD). Little is known about the frequency with which primary care physicians (PCPs) test for CD in patients with IDA. We aimed to describe how PCPs approach testing for CD in asymptomatic patients with IDA. METHODS We electronically distributed a survey to PCPs who are members of the American College of Physicians. Respondents were asked whether they would test for CD (serologic testing, refer for esophagogastroduodenoscopy [EGD], or refer to GI) in hypothetical patients with new IDA, including: (1) a young Caucasian man, (2) a premenopausal Caucasian woman, (3) an elderly Caucasian man, and (4) a young African American man. These scenarios were chosen to assess for differences in testing for CD based on age, gender, and race. Multivariable logistic regression was used to identify independent predictors of testing. RESULTS Testing for CD varied significantly according to patient characteristics, with young Caucasian men being the most frequently tested (61% of respondents reporting they would perform serologic testing in this subgroup (p<0.001)). Contrary to guideline recommendations, 80% of respondents reported they would definitely or probably start a patient with positive serologies for CD on a gluten free diet prior to confirmatory upper endoscopy. CONCLUSIONS PCPs are under-testing for CD in patients with IDA, regardless of age, gender, race, or post-menopausal status. The majority of PCPs surveyed reported they do not strictly adhere to established guidelines regarding a confirmatory duodenal biopsy in a patient with positive serology for CD.
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Affiliation(s)
- Marisa Spencer
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America
- * E-mail:
| | - Adrienne Lenhart
- Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, United States of America
| | - Jason Baker
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America
| | - Joseph Dickens
- Department of Statistics, University of Michigan, Ann Arbor, Michigan, United States of America
| | - Arlene Weissman
- Research Center, The American College of Physicians, Philadelphia, Pennsylvania, United States of America
| | - Andrew J. Read
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America
| | - Seema Saini
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America
- Ambulatory Care, Veterans Affairs Medical Center, Ann Arbor, Michigan, United States of America
| | - Sameer D. Saini
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America
- Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan, United States of America
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Smarrazzo A, Magazzù G, Ben-Hariz M, Legarda Tamara M, Velmishi V, Roma E, Kansu A, Mičetić-Turk D, Bravi E, Stellato P, Arcidiaco C, Greco L. Variability of anti-human transglutaminase testing in celiac disease across Mediterranean countries. World J Gastroenterol 2017; 23:4437-4443. [PMID: 28706427 PMCID: PMC5487508 DOI: 10.3748/wjg.v23.i24.4437] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2016] [Revised: 01/18/2017] [Accepted: 03/15/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To verify the precision and accuracy of transglutaminase antibodies (TGA) assays across Mediterranean countries.
METHODS This study involved 8 referral centres for celiac disease (CD) in 7 Mediterranean countries. A central laboratory prepared 8 kits of 7 blinded and randomized serum samples, with a titrated amount of Human TGA IgA. Each sample was analysed three times on three different days, with each centre running a total of 21 tests. The results were included in a blindly coded report form, which was sent to the coordinator centre. The coordinator estimated the mean coefficient of Variation (CoVar = σ/μ), the mean accuracy (Accur = Vobserved - Vreal) and the mean percent variation (Var% = [(Vobserved - Vreal)/Vreal] × 100).
RESULTS The analysis showed that 79.17% of the mean variation fell between -25% and +25% of the expected value, with the accuracy and precision progressively increasing with higher titres of TGA. From values 1.25 times greater than the normal cut-off, the measurements were highly reliable.
CONCLUSION TGA estimation is a crucial step for the diagnosis of CD; given its accuracy and precision, clinicians could be confident in establishing a diagnosis.
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Abstract
The incidence of celiac disease (CD) has increased over the last half-century, resulting in rising interest in identifying risk factors for CD. The necessity of duodenal biopsies in the diagnosis of CD has recently been challenged. Areas covered: This review covers the recent literature regarding the role of infant feeding practices, including breastfeeding and timing of gluten introduction, and the microbiota in the development of CD. Additionally, the application of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for a non-biopsy approach to the diagnosis of CD is reviewed. Expert commentary: Recent investigations have not revealed any significant effect of breastfeeding or timing of gluten introduction on the risk of CD in at-risk populations. There are alterations in the microbiota of CD patients. However, the role of the microbiome and whether its manipulation has a clinical effect are unknown. Preliminary data suggests a non-biopsy approach to diagnosis of pediatric CD can be applied to several populations, although additional studies are needed. Prospective investigations are underway to examine the interplay of infant feeding practices and the microbiome and to identify particular CD-specific biomarkers that may aid in the diagnosis and ultimately prevention of CD.
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Affiliation(s)
- Grace J Lee
- a Division of Pediatric Gastroenterology, Department of Pediatrics and Communicable Diseases , C.S. Mott Children's Hospital, University of Michigan , Ann Arbor , MI , USA
| | - John Y Kao
- b Division of Gastroenterology, Department of Internal Medicine , University of Michigan , Ann Arbor , MI , USA
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Liu E, Dong F, Barón AE, Taki I, Norris JM, Frohnert BI, Hoffenberg EJ, Rewers M. High Incidence of Celiac Disease in a Long-term Study of Adolescents With Susceptibility Genotypes. Gastroenterology 2017; 152:1329-1336.e1. [PMID: 28188747 PMCID: PMC5533620 DOI: 10.1053/j.gastro.2017.02.002] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2016] [Revised: 01/27/2017] [Accepted: 02/01/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Little is known about the incidence of celiac disease in the general population of children in the United States. We aimed to estimate the cumulative incidence of celiac disease in adolescents born in the Denver metropolitan area. METHODS We collected data on HLA-DR, DQ genotypes of 31,766 infants, born from 1993 through 2004 at St. Joseph's Hospital in Denver, from the Diabetes Autoimmunity Study in the Young. Subjects with susceptibility genotypes for celiac disease and type 1 diabetes were followed up for up to 20 years for development of tissue transglutaminase autoantibodies (tTGA). Outcomes were the development of celiac disease autoimmunity (CDA) or celiac disease. CDA was defined as persistence of tTGA for at least 3 months or development of celiac disease. Celiac disease was defined based on detection of Marsh 2 or greater lesions in biopsy specimens or persistent high levels of tTGA. For each genotype, the cumulative incidence of CDA and celiac disease were determined. To estimate the cumulative incidence in the Denver general population, outcomes by each genotype were weighted according to the frequency of each of these genotypes in the general population. RESULTS Of 1339 subjects followed up, 66 developed CDA and met criteria for celiac disease and 46 developed only CDA. Seropositivity for tTGA resolved spontaneously, without treatment, in 21 of the 46 subjects with only CDA (46%). The estimated cumulative incidence for CDA in the Denver general population at 5, 10, and 15 years of age was 2.4%, 4.3%, and 5.1%, respectively, and incidence values for celiac disease were 1.6%, 2.8%, and 3.1%, respectively. CONCLUSIONS In a 20-year prospective study of 1339 children with genetic risk factors for celiac disease, we found the cumulative incidence of CDA and celiac disease to be high within the first 10 years. Although more than 5% of children may experience a period of CDA, not all children develop celiac disease or require gluten-free diets.
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Affiliation(s)
- Edwin Liu
- Digestive Health Institute and Colorado Center for Celiac Disease, Children's Hospital Colorado, University of Colorado Denver, Aurora, Colorado; Barbara Davis Center, University of Colorado Denver, Aurora, Colorado.
| | - Fran Dong
- Barbara Davis Center, University of Colorado Denver
| | - Anna E. Barón
- Biostatics and Informatics, Colorado School of Public Health, University of Colorado Denver
| | - Iman Taki
- Barbara Davis Center, University of Colorado Denver
| | - Jill M. Norris
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver
| | | | - Edward J Hoffenberg
- Digestive Health Institute and Colorado Center for Celiac Disease, Children’s Hospital Colorado, University of Colorado Denver
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Higher Sensitivity and Earlier Identification of Celiac Disease Autoimmunity by a Nonradioactive Assay for Transglutaminase Autoantibodies. J Immunol Res 2017; 2016:2904563. [PMID: 28127566 PMCID: PMC5239972 DOI: 10.1155/2016/2904563] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Accepted: 12/06/2016] [Indexed: 12/03/2022] Open
Abstract
Higher sensitive transglutaminase autoantibody (TGA) assay will detect the onset of celiac disease (CD) autoimmunity earlier. In developing a nonradioactive assay for TGA, we utilized electrochemiluminescence (ECL) technology and compared it to a high-performance radioimmunoassay (RIA) currently being used to screen patients with type 1 diabetes (T1D) and genetically at-risk individuals for CD. We selected 183 T1D patients with 60 patients having received biopsy and analyzed 396 sequential samples from 73 young children longitudinally followed up with TGA seroconversion, with 27 undergoing biopsy. In addition, 112 age-matched healthy control subjects were included in the study. With the 99th percentile of specificity, the ECL assay detected significantly more TGA positivity among patients with T1D (133/183) than RIA (114/183) and more of the sequential samples (34%) from 73 children than RIA (18%). The TGA assay performed by ECL was positive in all 59 subjects with villous atrophy. Among 73 longitudinally followed up children, ECL assay had earlier detection of TGA on 34 children by a mean of 2.5 years. In conclusion, the new TGA assay by ECL has a higher sensitivity than the current RIA assay and may better predict the onset of CD.
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Rubio-Tapia A, Ludvigsson JF, Choung RS, Brantner TL, Rajkumar SV, Landgren O, Murray JA. Increased mortality among men aged 50 years old or above with elevated IgA anti-transglutaminase antibodies: NHANES III. BMC Gastroenterol 2016; 16:136. [PMID: 27809801 PMCID: PMC5093944 DOI: 10.1186/s12876-016-0547-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2016] [Accepted: 10/15/2016] [Indexed: 12/14/2022] Open
Abstract
Background Immunoglobulin A (IgA) antibodies to tissue transglutaminase (tTG) are the serologic test of choice for diagnosing celiac disease (CD). Our aim was to determine if elevated IgA anti-tTG were associated with increased mortality risk. Methods Stored serum samples of National Health and Nutrition Examination Survey (NHANES) III (1988–1992) were available for 6032 individuals aged 50 years old or above, which were screened for IgA anti-tTG, and if positive, for IgA endomysial antibodies. Mortality was determined from the National Death Index records through 2006. Hazard ratios were calculated through Cox proportional hazards regression. Results From a total of 6032, 85 participants tested positive for IgA anti-tTG (1.4 %) and 5947 tested negative. After a median follow-up of 13 years, IgA anti-tTG positive participants were at increased risk of death in both crude (HR = 1.68; 95 % CI = 1.30–2.18) and adjusted analyses (adjusted hazard ratio = 1.43; 95 % CI = 1.10–1.85) as compared to IgA anti-tTG negative participants. The excess mortality was restricted to IgA anti-tTG positive males (adjusted hazard ratio = 1.69 (95 % CI = 1.26–2.29), as opposed to a hazard ratio of 0.96 (95 % CI = 0.57–1.62) among IgA anti-tTG positive females. Although the most common cause of death in IgA anti-tTG positive participants was cardiovascular disease (36 %), the increased hazard ratio was only observed in respiratory cause of death as compared to IgA anti-tTG negative participants (adjusted hazard ratio = 5.11; 2.76–9.46). Conclusion Men aged 50 years old or above participants of NHANES III with elevated IgA anti-tTG antibodies had increased mortality risk. Elevated IgA anti-tTG antibodies could be a nonspecific marker of serious disease in older men.
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Affiliation(s)
- Alberto Rubio-Tapia
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA
| | - Jonas F Ludvigsson
- Deparment of Pediatrics, Orebro University Hospital, Orebro, Sweden.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Rok Seon Choung
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA
| | - Tricia L Brantner
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA
| | - S Vincent Rajkumar
- Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Ola Landgren
- Multiple Myeloma Section, Lymphoid Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.,Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.,National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
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Gesualdo PD, Bautista KA, Waugh KC, Yu L, Norris JM, Rewers MJ, Baxter J. Feasibility of screening for T1D and celiac disease in a pediatric clinic setting. Pediatr Diabetes 2016; 17:441-8. [PMID: 26251221 PMCID: PMC4979315 DOI: 10.1111/pedi.12301] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 07/02/2015] [Accepted: 07/06/2015] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE Type 1 diabetes (T1D) or celiac disease (CD) develops in at least 2% of the general population. Early detection of disease-specific autoimmunity and subsequent monitoring would be possible if screening tests were more widely available. Currently, screening for islet autoimmunity is available only in a research setting, and CD-specific autoimmunity screening is limited to those in high-risk groups. This study assessed the feasibility of incorporating T1D and CD autoantibody screening into a pediatric practice. METHODS Patient engagement strategies, blood collection preference, blood sample volume, rate of autoantibody detection in the general population, and parental satisfaction were assessed. Over 5 weeks, research staff recruited 200 patients, aged 2-6 yr from two pediatric practices in the Denver area to be screened for islet autoantibodies (IAs) and the transglutaminase antibody. RESULTS Of the 765 parents approached, 200 (26%) completed the same-day screening. Of the 565 subjects who did not complete the screening, 345 expressed interest, but were unable to make a participation decision. A finger stick, compared with a venous draw, was the preferred method of sample collection. Both methods yielded sufficient blood volume for autoantibody determination. IAs or the transglutaminase antibody were detected in 11 subjects. Parents expressed satisfaction with all aspects of participation. CONCLUSIONS The results of this study suggest that it is feasible to conduct this type of screening in a pediatric clinic. Such screening could lead to increased disease awareness and the possible benefits that can result from early detection.
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Affiliation(s)
- Patricia D. Gesualdo
- University of Colorado Denver, Barbara Davis Center for Diabetes, 1775 Aurora Court, Campus Box F527, Aurora, CO 80045
| | - Kimberly A. Bautista
- University of Colorado Denver, Barbara Davis Center for Diabetes, 1775 Aurora Court, Campus Box F527, Aurora, CO 80045
| | - Kathleen C. Waugh
- University of Colorado Denver, Barbara Davis Center for Diabetes, 1775 Aurora Court, Campus Box F527, Aurora, CO 80045
| | - Liping Yu
- University of Colorado Denver, Barbara Davis Center for Diabetes, 1775 Aurora Court, Campus Box F527, Aurora, CO 80045
| | - Jill M. Norris
- Department of Epidemiology, Colorado School of Public Health, 13001 East 17th Place, Campus Box B119, Aurora, CO 80045
| | - Marian J. Rewers
- University of Colorado Denver, Barbara Davis Center for Diabetes, 1775 Aurora Court, Campus Box F527, Aurora, CO 80045
| | - Judith Baxter
- University of Colorado Denver, Barbara Davis Center for Diabetes, 1775 Aurora Court, Campus Box F527, Aurora, CO 80045
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