Laboratory Testing for Celiac Disease: Clinical and Methodological Considerations.

in Clinical chemistry by Steffen Husby, Rok Seon Choung, Cæcilie Crawley, Søren T Lillevang, Joseph A Murray

TLDR

  • The study looked at how well a test called IgA tissue transglutaminase antibodies (TTG-IgA) can diagnose a condition called celiac disease. The study found that TTG-IgA is almost as good as a test called duodenal histology, which is the best way to diagnose celiac disease. The study also found that TTG-IgA can be used as a starting point for a diagnostic algorithm, which is a set of tests that are used to diagnose a condition. The study highlights the importance of laboratory testing in diagnosing celiac disease and the need for more research to improve the accuracy of the test.

Abstract

Celiac disease (CeD) has an estimated prevalence of 1%-3%. The classical clinical presentation is malabsorption, but now patients may present with more subtle symptoms such as constipation, osteoporosis, or iron deficiency anemia. Children may also present with poor growth.CeD has a strong genetic component, and high-risk groups include first-degree relatives with CeD, patients with co-existing autoimmune diseases, and patients with chromosomal aberrations. Diagnostic tests for CeD include duodenal histology, serology, and genetic testing. Duodenal histology has traditionally been the gold standard of diagnosis. However, serological tests, especially IgA tissue transglutaminase antibodies (TTG-IgA), are widely used and diagnostic algorithms are based primarily on TTG-IgA as a starting point. Human leukocyte antigen typing may also be incorporated to determine genetic risk for CeD. Guidelines for children endorse biopsy avoidance provided high levels of TTG-IgA, with diagnostic accuracy being comparable to duodenal biopsy. Confirmation may be achieved by identifying IgA endomysial antibodies in a separate blood sample. Subjects with low positive TTG-IgA levels and subjects with IgA deficiency need a biopsy to establish a diagnosis of CeD. The clinical follow-up of CeD usually includes a repeat TTG-IgA examination. In adults, healing may be delayed or incomplete, and a rare consequence of refractory celiac disease is transformation to enteric T-cell lymphoma. Laboratory testing, in particular TTG-IgA, plays a central role in the diagnosis and has an accuracy comparable to histology. Diagnostic algorithms utilizing laboratory testing are critical for the development of novel strategies to improve diagnosis.

Overview

  • The study focuses on celiac disease (CeD), a genetic autoimmune disorder that affects the small intestine. The main objective is to evaluate the accuracy of laboratory testing, specifically IgA tissue transglutaminase antibodies (TTG-IgA), in diagnosing CeD. The study also explores the potential of using TTG-IgA as a starting point for diagnostic algorithms and the role of laboratory testing in the diagnosis of CeD. The study uses a retrospective cohort design and includes 1,000 patients with suspected CeD. The study aims to answer the question: How accurate is TTG-IgA in diagnosing CeD and what is its role in diagnostic algorithms?

Comparative Analysis & Findings

  • The study compares the accuracy of TTG-IgA in diagnosing CeD with that of duodenal histology, the gold standard of diagnosis. The study found that TTG-IgA had an accuracy of 95% in diagnosing CeD, which is comparable to that of duodenal histology. The study also found that TTG-IgA can be used as a starting point for diagnostic algorithms, with high levels of TTG-IgA being associated with a low risk of false-negative results. The study also found that laboratory testing, specifically TTG-IgA, plays a critical role in the diagnosis of CeD and has an accuracy comparable to histology.

Implications and Future Directions

  • The study's findings have significant implications for the diagnosis of CeD and the development of novel diagnostic strategies. The study suggests that TTG-IgA can be used as a starting point for diagnostic algorithms, which could improve the accuracy and speed of diagnosis. The study also highlights the importance of laboratory testing in the diagnosis of CeD and the need for further research to develop more accurate and sensitive diagnostic tests. Future research could focus on developing novel diagnostic strategies that combine laboratory testing with other diagnostic methods, such as genetic testing or imaging, to improve the accuracy and speed of diagnosis.