Serum anti-tissue Transglutaminase IgA Shows High Specificity and Predictive Value for Celiac Disease Diagnosis

Celiac.com 09/27/2023 - A team of researchers recently set out to explore duodenal villous atrophy in adults with suspected celiac disease without IgA deficiency. The research team included Prof Carolina Ciacci, MD, Prof Julio Cesar Bai, MD, Geoffrey Holmes, MD, Abdulbaqi Al-Toma, MD, Prof Federico Biagi, MD, Prof Antonio Carroccio, MD, Rachele Ciccocioppo, MD, Prof Antonio Di Sabatino, MD, Rachel Gingold-Belfer, MD, Mariana Jinga, MD, Prof Govind Makharia, MD, Sonia Niveloni, MD, Gary L Norman, PhD, Kamran Rostami, MD, Prof David S Sanders, MD, Edgardo Smecuol, MD, Vincenzo Villanacci, MD, Santiago Vivas, MD, and Fabiana Zingone, MD, on behalf of theBi.A.CeD study group.

The team conducted a multi-center, prospective cohort study to assess the accuracy of serum anti-tissue transglutaminase IgA (tTG-IgA) in diagnosing celiac disease in adults. The study included adult participants aged 18 years or older, with suspected celiac disease, who were not on a gluten-free diet, and did not have IgA deficiency. 

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The participants were enrolled from 14 tertiary referral centers across different regions from February 27, 2018, to December 24, 2020. The main objective was to determine whether serum tTG-IgA tests could reliably diagnose celiac disease based on duodenal villous atrophy.

The study included 436 participants (296 women and 140 men) with complete data on serum tTG-IgA and duodenal histology. Of these, 363 participants had positive serum tTG-IgA results, and 73 had negative results. After local review, it was found that 341 of the participants with positive serum tTG-IgA had positive histology (true positives), while 22 had negative histology (false positives). Among the 73 participants with negative serum tTG-IgA, seven had positive histology (false negatives), and 66 had negative histology (true negatives) after local review.

Study Findings: Positive Predictive Value of 95.9% for Celiac Disease Serum tTG-IgA

The study's findings showed a positive predictive value of 93.9% and a negative predictive value of 90.4% for serum tTG-IgA in diagnosing celiac disease. The sensitivity was 98.0%, indicating the test's ability to correctly identify true positive cases, while the specificity was 75.0%.

After central re-evaluation of duodenal histology in discordant cases, the positive predictive value increased to 95.9%, and specificity improved to 81.5%. The sensitivity remained high at 98.0%.

The study also found that the positive predictive value of serum tTG-IgA increased as the serological threshold was defined at higher multiples of the upper limit of normal (ULN). The area under the receiver operating characteristic curve (AUC) for serum tTG-IgA was 0.87 for the categorical definition (positive vs. negative) and 0.93 for the numerical definition (multiples of the ULN) in predicting duodenal villous atrophy.

Conclusion

Based on the data, the study suggests that in adults with a reliable suspicion of celiac disease and high serum tTG-IgA levels, a biopsy may reasonably be avoided in the diagnostic process. This information can be valuable in improving the efficiency and accuracy of diagnosing celiac disease in certain cases, reducing the need for biopsy.

Read more in The Lancet Gastroenterology and Hepatology

Note: The researchers are variously affiliated with the Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Salerno, Italy; the Research Institutes, Universidad del Salvador, Buenos Aires, Argentina; the Small Bowel Section, Dr C Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina; Department of Gastroenterology, Royal Derby Hospital, Derby, UK; the Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, Netherlands; the Department of Internal Medicine and Medical Therapy, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy; the Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri, IRCCS, Pavia, Italy; the Unit of Internal Medicine, Cervello Hospital, University of Palermo, Palermo, Italy; the Gastroenterology Division, Rabin Medical Centre, Beilinson Hospital, Petah Tikva, Israel; the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; the Gastroenterology Department, Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital, Bucharest, Romania; the Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India; the Research and Development, Headquarters and Technology Centre for Autoimmunity, Werfen, San Diego, CA, USA; the Gastroenterology Unit, MidCentral DHB, Palmerston North, New Zealand; the Academic Unit of Gastroenterology, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK; the Institute of Pathology, Spedali Civili University of Brescia, Brescia, Italy; the Gastroenterology Unit, University Hospital of Leon, Leon, Spain; and the Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy, on behalf of the Bi.A.CeD study group.