Thermo Fisher – Coeliac Disease Testing

Managing IgA-deficient samples in coeliac disease testing – antibody testing to support the diagnosis of coeliac disease.

Celiac disease is a lifelong condition in which ingesting gluten causes chronic inflammation and damages small intestinal mucosa.¹ Tissue transglutaminase (tTG) is the major autoantigen in celiac disease,² and thus, IgA antibodies against tTG are disease-specific serological markers for both celiac disease and dermatitis herpetiformis.^{3, 4, 5} IgG antibodies against tTG are less specific but helpful markers in patients with IgA deficiency.^{6, 7, 8}

Testing guidelines aim to minimise false negatives

The guidelines established by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) provide a structured approach for diagnosing celiac disease. According to these guidelines, ESPGHAN advises that assessing total serum IgA along with IgA antibodies against tissue transglutaminase 2 (tTG-IgA) is more advantageous than using other testing combinations. IgG-based testing should be considered only if total IgA is low or undetectable.⁸ ESPGHAN advises against using deamidated gliadin peptide antibodies (DGP-IgG/IgA) for initial testing. Patients with positive results should then be referred to a paediatric gastroenterologist/specialist.⁸

References:

1. Mäki M and Collin P. Coeliac disease. Lancet, 1997; 349:1755–1759.
2. Dieterich W, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nature Med, 1997; 3:797–801.
3. Sulkanen S, et al. Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease. Gastroenterology, 1998; 115:1322–1328.
4. Troncone R, et al. IgA antibodies to tissue transglutaminase: An effective diagnostic test for celiac disease. J Pediatr, 1999; 134: 166–171.
5. Rose C, et al. Circulating autoantibodies to tissue transglutaminase differentiate patients with dermatitis herpetiformis from these with linear IgA disease. J Am AcadDermatol, 1999; 41:957–961.
6. Korponay-Szabó IR, et al. Elevation of IgG antibodies against tissue transglutaminase as a diagnostic tool for coeliac disease in selective IgA defi ciency. Gut, 2003; 52:1567–1571.
7. Agardh D, et al. Tissue transglutaminase immunoglobulin isotypes in children with untreated and treated celiac disease. J Pediatr Gastroenterol Nutr, 2003; 36:77–82.
8. Husby S, et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. J Pediatr Gastroenterol Nutr, 2020; 70:141–156.

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