The role of serology in the diagnosis of celiac disease Serology in celiac disease
Gastroenterology and Hepatology from Bed to Bench,
Vol. 16 No. 2 (2023),
21 Ordibehesht 2023
https://doi.org/10.22037/ghfbb.v16i2.2713
Abstract
Serology has significantly revolutionized the knowledge of celiac disease (CD), leading to the identification of unsuspected patients in at-risk CD groups, thereby increasing the number of CD diagnoses compared to the pre-screening era. Several markers for CD with a progressive diagnostic accuracy have been identified over the years, but only three of them, i.e. anti-tissue transglutaminase (anti-tTG), anti-endomysial (EmA) and anti-deamidated gliadin antibodies (DGP) are currently assessed in the daily clinical practice. A thorough review of the literature identified 44 original studies published between 1998 to 2022 for a total of 5098 pediatric and adult CD patients (without selective IgA deficiency) and 11930 disease controls. The results highlighted that anti-tTG IgA exhibited a higher sensitivity for CD (93.4%) than EmA IgA (92.8%), DGP IgG (81.8%) and DGP IgA (83.8%). The specificity of EmA IgA (99%) resulted to be higher than those of anti-tTG IgA (95.8%), DGP IgG (96.4%) and DGP IgA (92.1%). In patients with selective IgA deficiency, a condition closely related to CD, serological screening should include one of the three antibodies of IgG class, since anti-tTG, DGP and EmA have a very similar diagnostic accuracy in this clinical setting. According to age, there are two main diagnostic strategies for CD detection. In children, the revised ESPGHAN 2020 guidelines established that CD could be diagnosed in both symptomatic and asymptomatic children by high anti-tTG IgA titers (>10 times the cut-off) and EmA positivity with no need to obtain duodenal biopsy and HLA typing. In adult patients, although high tTG IgA titers (confirmed by EmA IgA positivity) correlate with villous atrophy, an intestinal biopsy is still considered mandatory for confirming CD diagnosis. Currently, a case finding approach in at-risk groups is preferred to mass screening for CD detection.
- celiac disease serology, antibodies anti tissue transglutaminase, antibodies anti-endomysial, antibodies anti-deamidated gliadin, case finding, mass screening
How to Cite
References
Lebwohl B, Rubio-Tapia A. Epidemiology, presentation and diagnosis of celiac disease. Gastoenterology 2021;160:63-75.
Volta U, Fabbri A, Parisi C, Piscaglia M, Caio G, Tovoli F, et al. Old and new serological tests for celiac disease screening. Exp Rev Gastroenterol Hepatol 2010;4:31-35.
Leffler DA, Schppan D. Update on serologic testing in celiac disease. Am J Gastroenterol 2010;105:2520-2524.
Rizzetto M, Doniach D. Types of ‘reticulin’ antibodies detected in human sera by immunofluorescence. J Clin Pathol 1973:26:841-851.
Volta U, Lenzi M, Lazzari R, Cassani F, Collina A, Bianchi FB, et al. Antibodies to gliadin detected by immunofluorescence and a micro-ELISA method: markers of active childhood and adult coeliac disease. Gut 1985:26:667-671.
Chorzelski TP, Sulej J, Tchorzewska H, Jablonska S, Beutner EH, Kumar V. IgA class endomysium antibodies in dermatitis herpetiformis and coeliac disease. Ann NY Acad Sciences 1983;420:325-334.
Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997;3:797-801.
Dieterich W, Laag E, Schopper H, Volta U, Ferguson A, Gillett H, et al. Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology 1998;115:1317-1321.
Wong RC, Wilson RJ, Steele RH, Radford-Smith G, Adelstein S. A comparison of 13 guinea pig and human anti-tissue transglutaminase antibody ELISA kits. J Clin Pathol 2002;55:488-494.
Singh P, Singh A, Silvester JA, Sachdeva V, Chen X, Xu H, et al. 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.
Aleanzi M, Demonte AM, Esper C., Garcilazo S, Waggener M. Celiac disease: antibody recognition against native and selectively deamidated gliadin peptides. Clin Chem 2001;47:2023-2028.
Niveloni S, Sugai E, Cabanne A, Vazquez H, Argonz J, Smecuol E, et al. Antibodies against synthetic deamidated gliadin peptides as predictors of celiac disease: prospective assessment in an adult population with a high pretest probability of disease. Clin Chem 2007;53:2186-2192.
Amarri S, Alvisi P, De Giorgio R, Gelli MC, Cicola R, Tovoli F, et al. Antibodies to deamidated gliadin peptides: an accurate predictor of coeliac disease in infancy. J Clin Immunol 2013;33:1027-1030.
Hill ID. What are the sensitivity and specificity of serologic test for celiac disease? Do sensitivity and specificity vary in different populations? Gastroenterology 2005:128:25-32.
Sulkanen S, Halttunen T, Laurila K, Kolho KL, Korponay-Szabò IR, Savilhati E, et al. Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease. Gastroenterology 1998;115:1322-1328.
Biagi F, Ellis HJ, Yiannakou JY, Brusco G, Swift GL, Smith PM, et al. Tissue transglutaminase antibodies in celiac disease. Am J Gastroenterol 1999;94:2187-2192.
Troncone R, Maurano F, Rossi M, Micillo M, Greco L, Auricchio R, et al. IgA antibodies to tissue transglutaminase: an effective diagnostic test for celiac disease. J Pediatr 1999;134:166-171.
Lock RJ, Pitcher MC, Unsworth DJ. IgA anti-tissue transglutaminase as a diagnostic marker of gluten sensitive enteropathy. J Clin Path 1999; 52:274-277.
Sardy M, Odenthal U, Karpati S, Paulsson M, Smyth N. Recombinant human tissue transglutaminase ELISA for the diagnosis of gluten-sensitive enteropathy. Clin Chem 1999;45:2142-2149.
Vitoria JC, Arrieta A, Arranz C, Ayesta A, Sojo A, Maruri N, et al. Antibodies to gliadin, endomysium, and tissue transglutaminase for the diagnosis of celiac disease. J Pediatr Gastroenterol Nutr 1999;29:571-574.
Stern M and Working Group on Serologic Screening for Celiac Disease. Comparative evaluation of serologic tests for celiac disease: a European initiative toward standardization. J Pediatr Gastroenterol Nutr 2000;31:513-519
Sblattero D, Berti I, Trevisiol C, Marzari R, Tommasini A, Bradbury A, et al. Human recombinant tissue transglutaminase ELISA: an innovative diagnostic assay for celiac disease. Am J Gastroenterol 2000;95:1253-1257.
Biagi F, Pezzimenti D, Campanella J, Vadacca GB, Corazza GR. Endomysial and tissue transglutaminase antibodies in coeliac sera: a comparison not influenced by previous serological testing. Scand J Gastroenterol 2001; 36:955-958.
Fabiani E, Catassi C, International Working Group on Eu-tTG. International Working Group.The serum IgA class anti-tissue transglutaminase antibodies in the diagnosis and follow up of coeliac disease. Results of an international multi-centre study. Eur J Gastroenterol Hepatol 2001;13:659-665.
Leon F, Camarero C, R-Pena R, Eiras P, Sanchez L, Baragaño M, et al. Anti-transglutaminase IgA ELISA: clinical potential and drawbacks in celiac disease diagnosis. Scand J Gastroenterol 2001;36:849-853.
Bardella MT, Trovato C, Cesana BM, Pagliari C, Gebbia C, Peracchi M. Serological markers for coeliac disease: is it time to change? Dig Liver Dis 2001;33:426-431.
Dahele AV, Aldhous MC, Humphreys K, Ghosh S. Serum IgA tissue transglutaminase antibodies in coeliac disease and other gastrointestinal diseases. Q J Med 2001;94:195-205.
Dickey W, McMillan SA, Hughes DF. Sensitivity of serum tissue transglutaminase antibodies for endomysial antibody positive and negative coeliac disease. Scand J Gastroenterol 2001;36:511-514.
Bonamico M, Tiberti C, Picarelli A, Mariani P, Rossi D, Cipolletta E, et al. Radioimmunoassay to detect antitransglutaminase autoantibodies is the most sensitive and specific screening method for celiac disease. Am J Gastroenterol 2001;96:1536-1540.
Carroccio A, Vitale G, Di Prima L, Chifari N, Napoli S, La Russa C, et al. Comparison of anti-transglutaminase ELISAs and an anti-endomysial antibody assay in the diagnosis of coeliac disease: a prospective study. Clin Chem 2002;48:1546-1550.
Burgin-Wolff A, Dahlbom I, Hadziselimovic F, Peterson CJ. Antibodies against human tissue transglutaminase and endomysium in diagnosing and monitoring coeliac disease. Scand J Gastroenterol 2002;37:685-691.
Tesei N, Sugai E, Vazquez H, Smecuol E, Niveloni, S, Mazure R, et al. Antibodies to human recombinant tissue transglutaminase may detect coeliac disease patients undiagnosed by endomysial antibodies. Aliment Pharmacol Therap 2003;17:1415-1423.
Llorente MJ, Sebastian M, Fernandez-Acenero MJ, Serrano G, Villanueva S. IgA antibodies against tissue transglutaminase in the diagnosis of coeliac disease: concordance with intestinal biopsy in children and adults. Clin Chem 2004;50:451-453.
Baudon JJ, Johanet C, Absalon YB, Morgant G, Cabrol S, Mougenot JF. Diagnosing celiac disease: a comparison of human tissue transglutaminase antibodies with antigliadin and antiendomysium antibodies. Arch Pediatr Adolesc Med 2004;158:584-588.
Collin P, Kaukinen K, Vogelsang H, Korponay-Szabò I, Sommer R, Scheier E, et al. Antiendomysial and antihuman tissue transglutaminase antibodies in the diagnosis of coeliac disease: a biopsy-proven European multicenter study. Eur J Gastroenterol Hepatol 2005;17:85-91.
Sugai E, Vázquez H, Nachman F, Moreno ML, Mazure R, Smecuol E, et al. Accuracy of tetsing for antibodies to synthetic gliadin-related peptides in celiac disease. Clin Gastroenterol Hepatol 2006;4:1112-1117.
Bazzigaluppi E, Roggero P, Parma B, Brambillasca MF, Meroni F, Mora S, et al. Antibodies to recombinant human tissue-transglutaminase in coeliac disease: diagnostic effectiveness and decline pattern after gluten-free diet. Dig Liver Dis 2006;38:98-102.
Agardh D. Antibodies against synthetic deamidated gliadin peptides and tissue transglutaminase for the identification of childhood celiac disease. Clin Gastroenterol Hepatol 2007;5:1276-1281.
Kaukinen K, Collin P, Laurila K, Kaartinen T, Partanen J, Maki M. Resurrection of gliadin antibodies in coeliac disease. Deamidated gliadin peptide antibody test provides additional diagnostic benefit. Scand J Gastroenterol 2007;42:1428-1433.
Ankelo M, Kleimola V, Simell S, Simell O, Knip M, Jokisalo E, et al. Antibody responses to deamidated gliadin peptide show high specificity and parallel antibodies to tissue transglutaminase in developing coeliac disease. Clin Exp Immunol 2007;150:285-293.
Hopper AD, Hadjivassiliou M, Hurlstone DP, Lobo AJ, McAlindon ME, Egner W, et al. What is the role of serologic testing in celiac disease? A prospective, biopsy-confirmed study with economic analysis. Clin Gastroenterol Hepatol 2008;6:314-320.
Volta U, Granito A, Fiorini E, Parisi C, Piscaglia M, Pappas G, et al. Usefulness of antibodies to deamidated gliadin peptides in celiac disease diagnosis and follow-up. Dig Dis Sci 2008;53:1582-1588.
Rashtak S, Ettore MW, Homburger HA, Murray JA. Comparative usefulness of deamidated gliadin antibodies in the diagnosis of celiac disease. Clin Gastroenterol Hepatol 2008;6:426-432.
Korponay-Szabó IR, Vecsei Z, Király R, Dahlbom I, Chirdo F, Nemes E, et al. Deamidated gliadin peptides form epitopes that transglutaminase antibodies recognize. J Pediatr Gastroenterol Nutr 2008;46:253-261.
Prause C, Ritter M, Probst C, Daehnrich C. Schlumberger W, Komorowski L, et al. Antibodies against deamidated gliadin as new and accurate biomarkers of childhood coeliac disease. J Pediatr Gastroenterol Nutr 2009;49:52-58.
Basso D, Guariso G, Fogar P, Meneghel A, Zambon CF, Navaglia F,et al. Antibodies against synthetic deamidated gliadin peptides for celiac disease diagnosis and follow-up in children. Clin Chem 2009;55:150-157.
Volta U, Granito A, Parisi C, Fabbri A, Fiorini E, Piscaglia M, et al. Deamidated gliadin peptide antibodies as a routine test for celiac disease: a prospective analysis. J Clin Gastroenterol 2010;44:186-190.
Dahle C, Hagman A, Ignatova S, Ström M. Antibodies against deamidated gliadin peptides identify adult coeliac disease patients negative for antibodies against endomysium and tissue transglutaminase. Aliment Pharmacol Ther 2010;32:254-260.
Sakly W, Mankaï A, Ghdess A, Achour A, Thabet Y, Ghedira I. Performance of anti-deamidated gliadin peptides antibodies in celiac disease diagnosis. Clin Res Hepatol Gastroenterol 2012;36:598-603.
Borroni G, Biagi F, Ciocca O, Vassallo C, Carugno A, Cananzi R, et al. IgA anti-epidermal transglutaminase autoantibodies: a sensible and sensitive marker for diagnosis of dermatitis herpetiformis in adult patients. J Eur Acad Dermatol Venereol 2013;27:836-841.
Srinivas M, Basumani P, Podmore G, Shrimpton A, Bardhan KD. Utility of testing patients, on presentation, for serologic features of celiac disease. Clin Gastroenterol Hepatol 2014;12:946-952.
Wolf J, Petroff D, Richter T, Auth MKH, Uhlig HH, Laass MW, et al. Validation of antibody-based strategies for diagnosis of pediatric celiac disease without biopsy. Gastroenterology 2017;153:410-419.
Ermarth A, Bryce M, Woodward S, Stoddard G, Book L, Jensen MK. Identification of pediatric patients with celiac disease based on serology and a classification and regression tree analysis. Clin Gastroenterol Hepatol 2017;15:396-402.
Gulseren YD, Adiloglu AK, Yucel M, Dag Z, Eyerci N, Berkem R, et al. Comparison of non-invasive tests with invasive tests in the diagnosis of celiac disease. J Clin Lan Anal 2019;33:22722.
Nemec G, Ventura A, Stefano M, Di Leo G, Baldas V, Tommasini A, et al. Looking for celiac disease: diagnostic accuracy of two rapid commercial assays. Am J Gastroenterol 2006;101:1597-1600.
Mooney PD, Kurien M, Evans KE, Chalkiadakis I, Hale MF, Kannan MZ, et al. Point-of-care testing for celiac disease has a low sensitivity in endoscopy. Gastrointest Endosc 2014:80:456-462.
Choung RS, Khaleghi Rostamkolaei S, Ju JM, Marietta EV, Van Dyke CT, Rajasekaran JJ, et al. Synthetic neoepitopes of the transglutaminase-deamidated gliadin complex as biomarkers for diagnosing and monitoring celiac disease. Gastroenterology 2019;156:582-591.
Lebwohl B, Rubio-Tapia A, Guandalini S, Newland C, Assiri A. Diagnosis of celiac disease. Gastrointest Endosc Clin N Am 2012;22:661-667.
Volta U, Caio G, Boschetti E, Giancola F, Rhoden KJ, Ruggeri E, et al. Seronegative celiac disease: shedding light on an obscure clinical entity. Dig Liver Dis 2016;48:1018-1022.
Schiepatti A, Sanders DS, Baiardi P, Caio G, Ciacci C, Kaukinen K, et al. Nomenclature and diagnosis of seronegative coeliac disease and chronic non-coeliac enteropathies in adults: the Paris consensus. Gut 2022;71:2218-2225.
Hill PG, Holmes GK. Coeliac disease: a biopsy is not always necessary for diagnosis. Aliment Pharmacol Ther 2008;27:572-577.
Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, Shamir R, et al. ESPGHAN working group on coeliac disease diagnosis. european society for pediatric gastroenterology, hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012;54:136-160.
Husby S, Koletzko S, Korponay-Szabó I, Kurppa K, Mearin ML, Ribes-Koninckx C, et al. European society paediatric gastroenterology, hepatology and nutrition guidelines for diagnosing coeliac disease. J Pediatr Gastroenterol Nutr 2020;70:141-156.
Egner W, Shrimpton A, Sargur R, Patel D, Swallow K. ESPGHAN guidance on coeliac disease 2012: multiples of ULN for decision making do not harmonise assay performance across centres. J Pediatr Gastroenterol Nutr 2012;55:733-35.
Fuchs V, Kurppa K, Huhtala H, Laurila K, Mäki M, Collin P, et al. Serology-based criteria for adult coeliac disease have excellent accuracy across the range of pre-test probabilities. Aliment Pharmacol Ther 2019;49:277-284.
Penny HA, Raju SA, Lau MS, Marks LJ, Baggus EM, Bai JC, et al. Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts. Gut 2021;70:876-883.
Collin, P. Should adults be screened for celiac disease? What are the benefits and harms of screening? Gastroenterology 2005;128:104-108.
Catassi C, Verdu EF, Bai JC, Lionetti E. Coeliac disease. Lancet 2022;399:2413-2426.
Volta U, Caio G, Giancola F, Rhoden KJ, Ruggeri E, Boschetti E, et al. Features and progression of potential celiac disease in adults. Clin Gastroenterol Hepatol 2016;14:686-693.
Villalta D, Tonutti E, Prause C, Koletzko S, Uhlig HH, Vermeersch P, et al. IgG antibodies against deamidated gliadin peptides for diagnosis of celiac disease in patients with IgA deficiency. Clin Chem 2010;56:464-468.
Pallav K, Xu H, Leffler DA, Kabbani T, Ciaran K. Immunoglobulin A deficiency in celiac disease in the United States. J Gastroenterol Hepatol 2016;31:133-137.
Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue'). Gastroenterology 1992;102:330-354.
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