Abstract
High efficient serological markers (SM) for celiac disease (CD) have evolved since the eighties thus completely modifying the approach to CD diagnosis. These celiac SM, i.e. tissue Transglutaminase (TG2), endomysial (EMA) and deamidated gliadin peptides (DGP) show different performance. Both IgA class TG2 (TGA-IgA) and EMA (EMA-IgA) display the highest accuracy. For EMA-IgA sensitivity in adults is slightly above 86% and the specificity close to 100%. In paediatric patients, sensitivity is ≥90%, and pooled specificity 98.2%. For TGA-IgA in the adult population sensitivity is above 95% and specificity in the range of 90%–96%, while in children sensitivity is around 90% and specificity around 95%. Measuring DGP antibodies, either IgA or IgG (DGPA-IgG/IgA) has a lower efficiency for CD diagnosis as compared to TGA and EMA, for all age groups. Contrary to other SM, DGPA-IgG perform better than IgA class tests. Only in IgA deficient individuals is an IgG based test indicated, preferably TGA-IgG or DGPA-IgG. If CD is suspected, measurement of total serum IgA and TGA-IgA is superior to other combinations and should be the initial step for initial testing at any age, while DGPA tests are not recommended because of their lower efficiency. In children and adolescents, due to their high accuracy, in absence of positive TGA/EMA CD diagnosis is unlikely, while in adults if the suspicion of CD is high, intestinal biopsy should be pursued even if SM are negative. Conversely children and adolescents with positive serology should be referred to a paediatric gastroenterologist to establish a firm diagnosis. On account of the high specificity of CD SM, patients with positive CD autoimmunity (TGA-IgA/EMA-IgA) but with mild histological changes (Marsh 0/I) should be followed carefully because of the risk of developing CD in the future.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
Abbreviations
- AGA:
-
Antigliadin antibodies
- ARA:
-
Antireticulin antibodies
- TGA-IgA:
-
IgA antibodies against type-2 (tissue) transglutaminase
- TGA-IgG:
-
IgG antibodies against type-2 (tissue) transglutaminase
- EMA-IgA:
-
IgA endomysial antibodies
- DGP:
-
Deamidated gliadin peptides
- ELISA:
-
Enzyme Immuno assay
- IF:
-
Immunofluorescence
- DGPA-IgG:
-
IgG Deamidated gliadin peptides antibodies
- DGPA-IgA:
-
IgA Deamidated gliadin peptides antibodies
- SM:
-
Serological marker
- SBB:
-
Small bowel biopsy
- TG2:
-
Tissue Transglutaminase
References
GW Meeuwisse 1970 Diagnostic criteria in celiac disease Acta Paediatr Scand 59 909 911
JA Walker-Smith S Guandalini J Schmitz 1990 Revised criteria for diagnosis of coeliac disease Arch Dis Child 65 909 911
S Husby S Koletzko IR Korponay-Szabó 2012 European society for pediatric gastroenterology, hepatology, and nutrition guidelines for the diagnosis of coeliac disease J Pediatr Gastroenterol Nutr 54 136 160
A Rubio-Tapia ID Hill CP Kelly 2013 ACG clinical guidelines: diagnosis and management of celiac disease Am J Gastroenterol 108 656 676
S Husby JA Murray DA Katzka 2019 AGA clinical practice update on diagnosis and monitoring of celiac disease—changing utility of serology and histologic measures: expert review Gastroenterology 156 885 889
S Husby S Koletzko I Korponay-Szabó 2020 European Society paediatric gastroenterology, hepatology and nutrition guidelines for diagnosing coeliac disease 2020 J Pediatr Gastroenterol Nutr 70 141 156
CR Koninckx JP Giliams I Polanco 1984 IgA antigliadin antibodies in celiac and inflammatory bowel disease J Pediatr Gastroenterol Nutr 3 676 682
R Troncone A Ferguson 1991 Anti-gliadin antibodies J Pediatr Gastroenterol Nutr 12 150 158
M Mäki O Hällström T Vesikari 1984 Evaluation of a serum IgA-class reticulin antibody test for the detection of childhood celiac disease J Pediatr 105 901 905
A Lecea De C Ribes-Koninckx I Polanco 1996 Serological screening (antigliadin and antiendomysium antibodies) for non-overt coeliac disease in children of short stature Acta Paediatr Int J Paediatr Suppl 85 54 55
E Grodzinsky G Jansson T Skogh 1995 Anti-endomysium and anti-gliadin antibodies as serological markers for coeliac disease in childhood: a clinical study to develop a practical routine Acta Pædiatrica 84 294 298
TM Rossi CH Albini V Kumar 1993 Incidence of celiac disease identified by the presence of serum endomysial antibodies in children with chronic diarrhea, short stature, or insulin-dependent diabetes mellitus J Pediatr 123 262 264
IR Korponay-Szabó JB Kovács A Czinner 1999 High prevalence of silent celiac disease in preschool children screened with IgA/IgG antiendomysium antibodies J Pediatr Gastroenterol Nutr 28 26 30
W Dieterich T Ehnis M Bauer 1997 Identification of tissue transglutaminase as the autoantigen of celiac disease Nat Med 3 797 801
CC Barker C Mitton G Jevon 2005 Can tissue transglutaminase antibody titers replace small-bowel biopsy to diagnose celiac disease in select pediatric populations? Pediatrics 115 1341 1346
I Dahlbom IR Korponay-Szabó JB Kovács 2010 Prediction of clinical and mucosal severity of coeliac disease and dermatitis herpetiformis by quantification of IgA/IgG serum antibodies to tissue transglutaminase J Pediatr Gastroenterol Nutr 50 140 146
Ø Molberg SN Mcadam R Körner 1998 Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease Nat Med 4 713 717
E Schwertz F Kahlenberg U Sack 2004 Serologic assay based on gliadin-related nonapeptides as a highly sensitive and specific diagnostic aid in celiac disease Clin Chem 50 2370 2375
K Giersiepen M Lelgemann N Stuhldreher 2012 Accuracy of diagnostic antibody tests for coeliac disease in children: summary of an evidence report J Pediatr Gastroenterol Nutr 54 229 241
MJ Gould H Brill MA Marcon 2019 In screening for celiac disease, deamidated gliadin rarely predicts disease when tissue transglutaminase is normal J Pediatr Gastroenterol Nutr 68 20 25
S Ferre-López C Ribes-Koninckx C Genzor 2004 Immunochromatographic sticks for tissue transglutaminase and antigliadin antibody screening in celiac disease Clin Gastroenterol Hepatol 2 480 484
P Singh A Arora TA Strand 2019 Diagnostic accuracy of point of care tests for diagnosing celiac disease: a systematic review and meta-analysis J Clin Gastroenterol 53 535 542
TP Chorzelski J Sulej H Tchorzewska 1983 IgA class endomysium antibodies in dermatitis herpetiformis and coeliac disease Ann N Y Acad Sci 420 325 334
Rostom A, Dubé C, Cranney A, et al. The diagnostic accuracy of serologic tests for celiac disease: a systematic review. Gastroenterology; 128. Epub ahead of print 2005. https://doi.org/10.1053/j.gastro.2005.02.028.
IR Korponay-Szabó I Dahlbom K Laurila 2003 Elevation of IgG antibodies against tissue transglutaminase as a diagnostic tool for coeliac disease in selective IgA deficiency Gut 52 1567 1571
Rostom A, Dubé C, Cranney A, et al. Celiac disease. Evidence report/technology assessment (Summary) 2004; 1–6.
Mascart-Lemone F, Lambrechts A. Serology of coeliac disease: early diagnosis and therapeutic impact. In: Acta gastro-enterologica belgica;1995. p. 388–96.
A Picarelli M Tola Di L Sabbatella 2001 Identification of a new coeliac disease subgroup: antiendomysial and anti-transglutaminase antibodies of IgG class in the absence of selective IgA deficiency J Intern Med 249 181 188
N Tesei E Sugai H Vázquez 2003 Antibodies to human recombinant tissue transglutaminase may detect coeliac disease patients undiagnosed by endomysial antibodies Aliment Pharmacol Ther 17 1415 1423
V Baldas A Ventura T Not 2000 Development of a novel rapid non-invasive screening test for coeliac disease Gut 47 628 631
P Collin K Kaukinen H Vogelsang 2005 Antiendomysial and antihuman recombinant tissue transglutaminase antibodies in the diagnosis of coeliac disease: a biopsy-proven European multicentre study Eur J Gastroenterol Hepatol 17 85 91
Werkstetter KJ, Korponay-Szabó IR, Popp A, et al. Accuracy in diagnosis of celiac disease without biopsies in clinical practice. Gastroenterology; 153. Epub ahead of print 2017. https://doi.org/10.1053/j.gastro.2017.06.002.
M Roca E Donat N Marco-Maestud 2019 Efficacy study of anti-endomysium antibodies for celiac disease diagnosis: a retrospective study in a Spanish pediatric population J Clin Med 8 2179
K Kurppa T Räsänen P Collin 2012 Endomysial antibodies predict celiac disease irrespective of the titers or clinical presentation World J Gastroenterol 18 2511 2516
A Mubarak VM Wolters SAM Gerritsen 2011 A biopsy is not always necessary to diagnose celiac disease J Pediatr Gastroenterol Nutr 52 554 557
L Lorand RM Graham 2003 Transglutaminases: crosslinking enzymes with pleiotropic functions Nat Rev Mol Cell Biol 4 140 156
LM Sollid B Jabri 2011 Celiac disease and transglutaminase 2: a model for posttranslational modification of antigens and HLA association in the pathogenesis of autoimmune disorders Curr Opin Immunol 23 732 738
D Sblattero F Florian E Azzoni 2002 The analysis of the fine specificity of celiac disease antibodies using tissue transglutaminase fragments Eur J Biochem 269 5175 5181
M Bonamico C Tiberti A Picarelli 2001 Radioimmunoassay to detect antitransglutaminase autoantibodies is the most sensitive and specific screening method for celiac disease Am J Gastroenterol 96 1536 1540
P Vermeersch K Geboes G Mariën 2013 Defining thresholds of antibody levels improves diagnosis of celiac disease Clin Gastroenterol Hepatol 11 398 403
E Liu M Li F Bao 2005 Need for quantitative assessment of transglutaminase autoantibodies for celiac disease in screening-identified children J Pediatr 146 494 499
M Stern 2000 Comparative evaluation of serologic tests for celiac disease: a European initiative toward standardization J Pediatr Gastroenterol Nutr 31 513 519
M Li L Yu C Tiberti 2009 A report on the international transglutaminase autoantibody workshop for celiac disease Am J Gastroenterol 104 154 163
E Zintzaras AE Germenis 2006 Performance of antibodies against tissue transglutaminase for the diagnosis of celiac disease: meta-analysis Clin Vaccine Immunol 13 187 192
A Carroccio G Vitale L Prima Di 2002 Comparison of anti-transglutaminase ELISAs and an anti-endomysial antibody assay in the diagnosis of celiac disease: a prospective study Clin Chem 48 1546 1550
R Chou C Bougatsos I Blazina 2017 Screening for celiac disease: evidence report and systematic review for the US preventive services task force JAMA—J Am Med Assoc 317 1258 1268
B Meensel Van M Hiele I Hoffman 2004 Diagnostic accuracy of ten second-generation (human) tissue transglutaminase antibody assays in celiac disease Clin Chem 50 2125 2135
SL Vriezinga R Auricchio E Bravi 2014 Randomized feeding intervention in infants at high risk for celiac disease N Engl J Med 371 1304 1315
F Cataldo D Lio V Marino 2000 IgG1 antiendomysium and IgG antitissue transglutaminase (anti-tTG) antibodies in coeliac patients with selective IgA deficiency Gut 47 366 369
Villalta D, Alessio MG, Tampoia M, et al. Diagnostic accuracy of IgA anti-tissue transglutaminase antibody assays in celiac disease patients with selective IgA deficiency. In: Annals of the New York academy of sciences. Blackwell Publishing Inc.;2007. p. 212–20.
A Tursi G Brandimarte GM Giorgetti 2003 Prevalence of antitissue transglutaminase antibodies in different degrees of intestinal damage in celiac disease J Clin Gastroenterol 36 219 221
Diamanti A, Colistro F, Calce A, et al. Clinical value of immunoglobulin A antitransglutaminase assay in the diagnosis of celiac disease. Pediatrics; 118. Epub ahead of print December 2006. https://doi.org/10.1542/peds.2006-0604.
Vivas S, Ruiz De Morales JG, Riestra S, et al. Duodenal biopsy may be avoided when high transglutaminase antibody titers are present. World J Gastroenterol 2009; 15: 4775–80.
MR Donaldson LS Book KM Leiferman 2008 Strongly positive tissue transglutaminase antibodies are associated with Marsh 3 histopathology in adult and pediatric celiac disease J Clin Gastroenterol 42 256 260
PG Hill GKT Holmes 2008 Coeliac disease: a biopsy is not always necessary for diagnosis Aliment Pharmacol Ther 27 572 577
S Castellaneta E Piccinno M Oliva 2015 High rate of spontaneous normalization of celiac serology in a cohort of 446 children with type 1 diabetes: a prospective study Diabetes Care 38 760 766
F Ferrara S Quaglia I Caputo 2010 Anti-transglutaminase antibodies in non-coeliac children suffering from infectious diseases Clin Exp Immunol 159 217 223
HJ Freeman 2004 Strongly positive tissue transglutaminase antibody assays without celiac disease Can J Gastroenterol 18 25 28
Garcia-Peris M, Donat Aliaga E, Roca Llorens M, et al. Anti-tissue transglutaminase antibodies not related to gluten intake. An Pediatr. Epub ahead of print 2018. https://doi.org/10.1016/j.anpedi.2018.01.013.
Wolf J, Haendel N, Remmler J, et al. Hemolysis and IgA-antibodies against tissue transglutaminase: When are antibody test results no longer reliable? J Clin Lab Anal; 32. Epub ahead of print 1 May 2018. https://doi.org/10.1002/jcla.22360.
ID Hill MH Dirks GS Liptak 2005 Guideline for the diagnosis and treatment of celiac disease in children: Recommendations of the North American Society for pediatric gastroenterology, hepatology and nutrition J Pediatr Gastroenterol Nutr 40 1 19
D Agardh 2007 Antibodies against synthetic deamidated gliadin peptides and tissue transglutaminase for the identification of childhood celiac disease Clin Gastroenterol Hepatol 5 1276 1281
E Sugai H Vázquez F Nachman 2006 Accuracy of testing for antibodies to synthetic gliadin-related peptides in celiac disease Clin Gastroenterol Hepatol 4 1112 1117
Brusca I. Overview of biomarkers for diagnosis and monitoring of celiac disease. In: Adv Clin Chem. Academic Press Inc.;2015. p. 1–55.
I Brusca A Carroccio E Tonutti 2012 The old and new tests for celiac disease: which is the best test combination to diagnose celiac disease in pediatric patients? Clin Chem Lab Med 50 111 117
D Basso G Guariso P Fogar 2009 Antibodies against synthetic deamidated gliadin peptides for celiac disease diagnosis and follow-up in children Clin Chem 55 150 157
S Simell A Kupila S Hoppu 2005 Natural history of transglutaminase autoantibodies and mucosal changes in children carrying HLA-conferred celiac disease susceptibility Scand J Gastroenterol 40 1182 1191
O Olen AH Gudjónsdóttir L Browaldh 2012 Antibodies against deamidated gliadin peptides and tissue transglutaminase for diagnosis of pediatric celiac disease J Pediatr Gastroenterol Nutr 55 695 700
E Liu M Li L Emery 2007 Natural history of antibodies to deamidated gliadin peptides and transglutaminase in early childhood celiac disease J Pediatr Gastroenterol Nutr 45 293 300
K Kurppa K Lindfors P Collin 2011 Antibodies against deamidated gliadin peptides in early-stage celiac disease J Clin Gastroenterol 45 673 678
L Mozo J Gómez E Escanlar 2012 Diagnostic value of anti-deamidated gliadin peptide IgG antibodies for celiac disease in children and IgA-deficient patients J Pediatr Gastroenterol Nutr 55 50 55
LCB Baviera ED Aliaga L Ortigosa 2007 Celiac disease screening by immunochromatographic visual assays: results of a multicenter study J Pediatr Gastroenterol Nutr 45 546 550
IR Korponay-Szabó K Szabados J Pusztai 2007 Population screening for coeliac disease in primary care by district nurses using a rapid antibody test: diagnostic accuracy and feasibility study Br Med J 335 1244 1247
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Ribes-Koninckx, C., Roca, M., Donat, E. (2022). Value and Use of Serologic Markers of Celiac Disease. In: Amil-Dias, J., Polanco, I. (eds) Advances in Celiac Disease . Springer, Cham. https://doi.org/10.1007/978-3-030-82401-3_6
Download citation
DOI: https://doi.org/10.1007/978-3-030-82401-3_6
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-82400-6
Online ISBN: 978-3-030-82401-3
eBook Packages: MedicineMedicine (R0)