Serological Update on Celiac Disease Diagnostics in Adults

Tsvetelina V. Velikova^1, , Zoya A. Spassova², Kalina D. Tumangelova-Yuzeir³, Ekaterina K. Krasimirova³, Ekaterina I. Ivanova-Todorova³, Dobroslav S. Kyurkchiev³ and Iskra P. Altankova¹

¹Clinical Immunology, University Hospital “Lozenetz”, Sofia 1407, Bulgaria

²Clinic of Gastroenterology, University Hospital “St. Ivan Rilski”, Medical University, Sofia 1431, Bulgaria

³Laboratory of Clinical Immunology, University Hospital “St. Ivan Rilski”, Department of clinical laboratory and clinical immunology, Medical University, Sofia 1431, Bulgaria

Cite this paper:
Tsvetelina V. Velikova, Zoya A. Spassova, Kalina D. Tumangelova-Yuzeir, Ekaterina K. Krasimirova, Ekaterina I. Ivanova-Todorova, Dobroslav S. Kyurkchiev and Iskra P. Altankova. Serological Update on Celiac Disease Diagnostics in Adults. International Journal of Celiac Disease. 2018; 6(1):20-25. doi: 10.12691/ijcd-6-1-8

Abstract

Celiac disease (CD) is an inflammatory disorder of the small intestines which serological diagnosis has come to the forefront with the development of the immunological testing. We aimed to explore the performance characteristics of a panel of serological tests in patients with CD. We assessed the serum levels of anti-tissue transglutaminase (anti-tTG), anti-deamidated gliadin peptides (anti-DGP), anti-actin (AAA), anti-gliadin antibodies (AGA) and cytokine IL-17A by performing ELISA; and anti-tTG, AGA and anti-Saccharomyces cerevisiae antibodies (ASCA) by immunoblot in 35 newly diagnosed adult patients with biopsy-proven CD and 25 age- and sex-matched healthy persons. The average serum levels of anti-tTG, anti-DGP, AGA, AAA, and ASCA were at significantly higher levels in patients with CD compared to healthy persons (p<0.001). We also observed that the serum level of IL-17A was about 70 times higher in CD patients than in the healthy persons (p=0.027). Anti-DGP antibodies showed highest diagnostic sensitivity (100%), followed by AGA and anti-tTG antibodies within the CD group. ROC curve analysis revealed the excellent performance of anti-DGP, anti-tTG, and AGA in the diagnosis of CD patients (AUC 1.000, 0.994, 0.992 respectively, p<0.001). Although the diagnosis of CD relays on biopsy, immunological serological testing could be employed with advantages in diagnosis and monitoring of CD patients.

Keywords:
celiac disease autoantibodies anti-tTG anti-DGP anti-F-actin antibodies anti-gliadin antibodies IL-17A

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Kaswala, D.H., Veeraraghavan, G., Kelly, C.P., Leffler, D.A., “Celiac Disease: Diagnostic Standards and Dilemmas,” Diseases, 3. 86-101. June 2015.
[2]	Dias, J.A., “Celiac Disease: What Do We Know in 2017?,” GE Port J Gastroenterol, 24. 275-278. November 2017.
[3]	Arslan, N., “Towards Finding More Diagnostic Serological Markers in Celiac Disease: Can Deamidated Gliadin Peptide Antibodies Help to Our Babies?,” International Journal of Celiac Disease, 1 (1). 27-28. 2013.
[4]	Sugai, E., Moreno, M.L., Hwang, H.J., Cabanne, A., Crivelli, A., Nachman, F., Vázquez, H., Niveloni, S., Argonz, J., Mazure, R., La Motta, G., Caniggia, M.E., Smecuol, E., Chopita, N., Gómez, J.C., Mauriño, E., Bai, J.C., “Celiac disease serology in patients with different pretest probabilities: Is biopsy avoidable?,” World J Gastroenterol, 16 (25). 3144-3152. July 2010.
[5]	Shannahan, S., Leffler, D.A., “Diagnosis and Updates in Celiac Disease,” Gastrointest Endoscopy Clin N Am, 27 (2017). 79-92. January 2017.
[6]	Vermeersch, P., Geboes, K., Mariën, G., Hoffman, I., Hiele, M., Bossuyt. X., “Diagnostic performance of IgG anti-deamidated gliadin peptide antibody assays is comparable to IgA anti-tTG in celiac disease,” Clinica Chimica Acta, 411 (2010). 931-935. February 2010.
[7]	Granito, A., Muratori, P., Cassani, F., et al., “Anti-actin IgA antibodies in severe coeliac disease,” Clin Exp Immunol, 137 (2). 386-392. August 2004.
[8]	Leffler, D.A., Schuppan, D., “Update on Serologic Testing in Celiac Disease,” Am J Gastroenterol, 105. 2520-2524. December 2010.
[9]	Ortega, C., Fernandez, S., Estevez, O.A., Aguado, R., Molina, I.J., Santamarıa, M., “IL-17 Producing T Cells in Celiac Disease: Angels or Devils?,” International Reviews of Immunology, 32. 534-543. September 2013.
[10]	Cicerone, C., Nenna, R., Pontone, S., “Th17, intestinal microbiota and the abnormal immune response in the pathogenesis of celiac disease,” Gastroenterol Hepatol Bed Bench, 8 (2). 117-122. March 2015.
[11]	Dieterich, W., Ehnis, T., Bauer, M., Donner, P., Volta, U., Riecken, E.O., Schuppan, D., “Identification of tissue transglutaminase as the autoantigen of celiac disease,” Nat. Med. 3. 797-801. July 1997.
[12]	Giersiepen, K., Lelgemann, M., Stuhldreher, N., Ronfani, L., Husby, S., Koletzko, S., Korponay-Szabу, I.R., ESPGHAN Working Group on Coeliac Disease Diagnosis, “Accuracy of diagnostic antibody tests for coeliac disease in children: summary of an evidence report,” J Pediatr Gastroenterol Nutr 54. 229-241. February 2012.
[13]	Schyum, A.C., Rumessen, J.J., “Serological testing for celiac disease in adults,” United European Gastroenterology Journal, 1 (5). 319-325. October 2013.
[14]	Schwertz, E., Kahlenberg, F., Sack, U., et al., “Serologic assay based on gliadin-related nonapeptides as a highly sensitive and specific diagnostic aid in celiac disease,” Clin Chem, 50. 2370-5. October 2004.
[15]	Carrocio, A., Brusca, I., Iacono, G., et al., “IgA anti-actin antibodies ELISA in coeliac disease: a multicenter study,” Dig Liver Dis, 39 (9). 818-823. September 2007.
[16]	Granito, A., Zauli, D., Muratori, P., et al., “Anti‐Saccharomyces cerevisiae and perinuclear anti‐neutrophil cytoplasmic antibodies in coeliac disease before and after gluten free diet,” Aliment Pharmacol Ther 2. 1881-887. April 2005.
[17]	Lerner, A., Jeremias, P., Matthias, T., “Outside of Normal Limits: False Positive/Negative Anti TG2 Autoantibodies,” International Journal of Celiac Disease, 3 (3). 87-90. July 2015.
[18]	Monzani, A., Rapa, A., Fonio, A., Tognato, E., Panigati, L., Oderda, G., “Use of deamidated gliadin peptide antibodies to monitor diet compliance in childhood celiac disease,” J pediatr gastroeneterol nutr, 53 (1). 55-60. July 2011.
[19]	Mazzarella, G., “Effector and suppressor T cells in celiac disease,” World J Gastroenterol, 21 (24). 7349-7356. June 2015.
[20]	Monteleone, I., Sarra, M., Del Vecchio Blanco, G., Paoluzi, O.A., Franze, E., Fina, D., Fabrizi, A., MacDonald, T.T., Pallone, F., Monteleone, G., “Characterization of IL-17A–Producing Cells in Celiac Disease Mucosa,” J Immunol, 184. 2211-2218. February 2015.