Coeliac disease (also gluten-sensitive enteropathy (GSE)) is a systemic autoimmune disease with pronounced genetic disposition which may affect several organ systems. The prevalence of the disease is estimated to be 1%, with experts suggesting a large number of undiagnosed cases due to “untypical” or only mild symptoms. In most cases, coeliac disease manifests with severe inflammation and damage to the mucous membrane of the small intestine (enteropathy). In conjunction with the resulting disturbed nutrient uptake, a broad spectrum of clinical gastrointestinal and non-gastrointestinal symptoms can occur (e.g. chronic diarrhoea, vomiting, abdominal pain, dwarfism, weight loss, delayed puberty, abortions, anaemia and osteoporosis). Moreover, the clinical manifestation of coeliac disease includes a possible chronic eczema, i.e. dermatitis herpetiformis.
Coeliac disease is caused by an overreaction of the immune system after intake of gluten, especially of the gliadin, which accounts for approximately 90% of the protein in many grains. Gliadin can only be partially digested in the small intestine. If the intestinal epithelial cells present gaps, as is the case in patients with coeliac disease, the gliadin fragments resulting from digestion may pass the intestinal barrier and enter the underlying connective tissue. There, the enzyme tissue transglutaminase (tTG) deamidates the amino acid glutamine into glutamic acid (at specific loci of the gliadin peptides). With this modification, the peptides gain their immunological properties when there is a genetic predisposition. There are two genetic variants (DQ2 and DQ8) of the human leukocyte antigen (HLA) system (HLA) which are particularly associated with the immune reaction. The activation of B cells then leads to the production of antibodies against the deamidated gliadin peptides (DGP) and the body’s own tTG. In addition, T cells secrete proinflammatory cytokines which cause an inflammatory reaction in the tissue.
According to the guidelines of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) there are different algorithms (Husby et al., 2020) for diagnostics of coeliac disease. Patients with respective symptoms should by investigated especially for anti-tTG antibodies (IgA) and total IgA antibodies. Moreover, the guidelines also underline the relevance of antibodies against endomysium (EmA) and the additional benefit of coeliac disease specific IgG-based tests, such as tests for the detection of antibodies against DGP.
EmA are considered very specific and sensitive markers for diagnostics of coeliac disease. They can be detected by indirect immunofluorescence test on tissue sections of primate liver, primate oesophagus, or primate intestine. The target antigen of EmA is tTG. Anti-tTG antibodies can be detected by ELISA or EUROLINE immunoblot. Moreover, DGP can be detected by ELISA, EUROLINE and the monospecific EUROPLUS substrate. Especially anti-tTG antibodies (IgA) and EmA (IgA) are essential for diagnostics. If there is a general IgA deficiency – which occurs more frequently than average in patients with coeliac disease – DGP (IgG) are considered an important alternative indicator for coeliac disease. In addition, EUROIMMUN offers HLA-DQ2/DQ8 detection by EUROArray – with a negative result, coeliac disease is virtually excluded.