It is well known that serology is an important tool in the diagnosis of Celiac Disease (CD), but the best way to use it is still a recurring doubt in the outpatient routine.
Each patient must be well evaluated before defining the best strategy. In patients with low probability of CD, for example, it is not recommended to combine several autoantibodies. Although this conduct increases sensitivity, it decreases specificity for diagnosis and, for this reason, it is not a good option in this group of patients.
On the other hand, when we are facing a patient with a high probability of the disease, even if the autoantibodies are negative, the investigation should continue with the performance of duodenal biopsies.
If you still do not know the pathophysiology of Celiac Disease, it is worth checking out this post (click here) before studying the related autoantibodies.
Autoantibodies in Celiac Disease
| Antigen | Antibody | Sensitivity % | Specificity % |
| Gliadin | IgA IgG |
85 (57-100) 80 (42-100) |
90 (47-94) 80 (50-94) |
| Endomysium | IgA IgG |
95 (86-100) 80 (70-90) |
99 (97-100) 97 (95-100) |
| Tissue transglutaminase | IgA IgG |
98 (78-100) 70 (45-95) |
98 (90-100) 95 (94-100) |
| Deaminated Gliadin | IgA IgG |
88 (74-100) 80 (70-95) |
90 (80-95) 98 (95-100) |
The antigliadin antibody has been used for decades in the diagnosis of CD, but its utility is quite limited today due to its low performance compared to other available tests.
The tissue transglutaminase IgA (anti-tTG IgA) is the first-line autoantibody because it has the highest sensitivity and is widely available. The higher its title, the greater the chance of CD and the greater the duodenal lesion. Titles greater than 5 times the upper limit of normal (ULN) have a high positive predictive value.
Due to the possible association of celiac disease with IgA deficiency, the collection of anti-tTG IgA should preferably be associated with the dosage of total IgA (especially in patients with a high probability of the disease). Another option is to associate the research of an IgG class autoantibody.
The deaminated gliadin or deaminated is an autoantibody against gliadin that came into contact with the tissue transglutaminase enzyme and underwent the process of deamination (release of its amine group). The association of anti-tTG IgA with deaminated gliadin IgG has shown the best performance (sensitivity and specificity) for the diagnosis of CD, but the research of this autoantibody is more expensive and little available in our environment currently. Thus, a good option is the association with anti-transglutaminase IgG, for example.
The anti-endomysium IgA antibody is the antibody with the best specificity (approximately 100%) and therefore has an important role in diagnostic confirmation (especially in patients with anti-tTG IgA with titles less than 2 times the ULN).
Performance of serological tests
The performance of serological tests in clinical practice is worse than in many of the major trials, as studies are usually conducted in a population with a high prevalence of CD. In addition, it is also important to remember that performance depends on the maintenance of a gluten diet. About 80% of patients negate autoantibodies in 6 to 12 months and more than 90% in 5 years. Weakly positive patients may negate their autoantibodies within a few weeks of dieting. It is rare that these autoantibodies do not normalize in the long term with a gluten-free diet. If this happens, it is necessary to rule out that gluten consumption is not happening unconsciously.
In the last decade, many studies have been conducted with POCTs (point-of-care tests). These are quick tests that can be used both in the endoscopy sector and in the office. A meta-analysis published in 2019 found sensitivity and specificity of 94 and 94.4% respectively, considering histology as the gold standard. Despite these results showing high sensitivity and specificity, due to the great variety of work done and conflicting results, more studies are still suggested before using them in clinical practice. For now, the use of POCTs should still be reserved for places with limited access to laboratories.
Studies are also being conducted with research of autoantibodies in saliva for screening in children suspected of CD. Despite the favorable results, showing a non-invasive, cheap and reproducible option, the evidence so far is not sufficient to recommend its use.
On the other hand, the detection of autoantibodies in feces does not seem to be useful in disease screening, with work showing a sensitivity of only 10%.
Given that autoantibodies in CD are produced in the small intestine itself, work is being done with research of autoantibodies in the supernatant of the duodenal biopsy. This research seems to have its importance mainly in the diagnosis of patients in the early stages of the disease, when serum autoantibodies may still be negative. But more studies are still needed to confirm its role in clinical practice.
Conclusion
Autoantibodies are extremely relevant exams for the diagnosis of CD. However, there is no single algorithm to define which autoantibody to request. In addition to knowing the sensitivity and specificity of each of them, it is necessary to evaluate the pre-test probability of the disease in each patient and the accessibility to the different available exams to define the best strategy.
References
- Green P, Stavropoulos S, Panagi SG, Goldstein S. Characteristics of adult celiac disease in the USA: results of a national survey. Am J Gastroenterol 2001;96:126– 131.
- Sanders DS. Changing face of adult coeliac disease: experience of a single university hospital in South Yorkshire. Postgrad Med J 2002;78(915):31–33.
- Al-Toma A , Volta U, Auricchio R, Castillejo G, Sanders D, Cellier C, Mulder C, Lundin K. European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European Gastroenterol J . 2019;7(5):583-613.
- Singh P, Arora A, Strand T, Leffler D, Mäki M, Kelly C, Ahuja V, Makharia G. Diagnostic Accuracy of Point of Care Tests for Diagnosing Celiac Disease: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2019;53(7):535-542.
- De Leo L, Bramuzzo M, Ziberna F, Villanacci V, Martelossi S, Di Leo G, Zanchi C, Giudici F, Pandullo M, Riznik P, Di Mascio A, Ventura A, Not T. Diagnostic accuracy and applicability of intestinal auto-antibodies in the wide clinical spectrum of coeliac disease. EBioMedicine . 2020 Jan;51:102567
How to cite this article
Vilela E. The role of autoantibodies in the diagnosis of celiac disease. Gastropedia 2023, Vol 1. Available at: https://gastropedia.com.br/gastroenterology/the-role-of-autoantibodies-in-the-diagnosis-of-celiac-disease
