Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2017; 23(24): 4437-4443
Published online Jun 28, 2017. doi: 10.3748/wjg.v23.i24.4437
Variability of anti-human transglutaminase testing in celiac disease across Mediterranean countries
Andrea Smarrazzo, Giuseppe Magazzù, Mongi Ben-Hariz, Maria Legarda Tamara, Virtut Velmishi, Elefhteria Roma, Aydan Kansu, Dušanka Mičetić-Turk, Enzo Bravi, Pio Stellato, Carmela Arcidiaco, Luigi Greco
Andrea Smarrazzo, Pio Stellato, Carmela Arcidiaco, Luigi Greco, Department of Translational Medical Sciences, School of Medicine, Section of Pediatrics, University of Naples “Federico II”, 80131 Naples, Italy
Andrea Smarrazzo, Pio Stellato, Carmela Arcidiaco, Luigi Greco, European Laboratory for Food Induced Diseases, 80131 Naples, Italy
Giuseppe Magazzù, Celiac Regional Centre, Pediatric Gastroenterology and Cystic Fibrosis Unit, University of Messina, 98125 Messina, Italy
Mongi Ben-Hariz, Pediatric Unit, Mongi SLIM’s Hospital of Tunis, 2046 SidiDaoud, La Marsa, Tunisie
Maria Legarda Tamara, Paediatric Gastroenterology Unit, Cruces University Hospital, 48903 Barakaldo, Spain
Virtut Velmishi, Service of Pediatric Gastroenterology "Mother Teresa" Hospital, 1000 Tirana, Albania
Elefhteria Roma, First Department of Pediatrics, University of Athens, 11527 Athens, Greece
Aydan Kansu, Department of Pediatric Gastroenterology, School of Medicine, Ankara University, Ankara 06100, Turkey
Dušanka Mičetić-Turk, University Medical Centre, Paediatric Department, 2000 Maribor, Slovenia
Enzo Bravi, Eurospital SpA, 34147 Trieste, Italy
Author contributions: Smarrazzo A, Magazzù G, Legarda Tamara M, Stellato P, Greco L, Ben-Hariz M, Velmishi V, Roma E, Kansu A, Mičetić-Turk D and Arcidiaco C contributed to the conception and design of the study and acquisition of data; Smarrazzo A and Greco L collected and analysed all the data, wrote the manuscript and provided statistical analysis of the data; Magazzù G, Legarda Tamara M and Stellato P helped to draft and critically revised the manuscript; Bravi E produced the testing sera and distributing the materials.
Supported by Italian Department of Health, Direction of International Affairs; Euromed action. Project: MEDICEL-Mediterranean Network for Celiac Disease-Phase II (CUP No. E61J11000450001); European Laboratory for Food Induced Disease, Federico II University, Naples.
Institutional review board statement: the study was reviewed and approved by all the authors. The final review was approved by ELFID Council.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at and.smarrazzo@libero.it. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Andrea Smarrazzo, MD, Department of Translational Medical Sciences, School of Medicine, Section of Pediatrics, University of Naples “Federico II”, Via Sergio Pansini 5, 80131 Naples, Italy. and.smarrazzo@libero.it
Telephone: +39-81-7463275 Fax: +39-81-7462375
Received: November 20, 2016
Peer-review started: November 22, 2016
First decision: December 19, 2016
Revised: January 18, 2017
Accepted: March 15, 2017
Article in press: March 15, 2017
Published online: June 28, 2017
Processing time: 217 Days and 17.1 Hours
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.

Keywords: Coeliac disease; Gluten; Transglutaminase; Non-invasive testing; Accuracy; Precision

Core tip: The “epidemic” of celiac disease (CD) across Mediterranean countries stimulated the need to standardize commonly used diagnostic tests. The titre of anti-transglutaminase antibodies has a strong relevance in the diagnosis of CD as defined by the ESPGHAN criteria; few studies, at the moment, estimated the variability of the main diagnostic tool for CD, in terms of accuracy and precision. Our study represents the first quality control work on this subject, with strong implication especially in countries with limited resources, where duodenal biopsy is not so easily performed.