Coeliac disease is an autoimmune disease that is triggered by gluten, which is contained in many types of cereals (wheat, rye, barley, etc.). It occurs in genetically predisposed individuals and results in a lifelong enteropathy. It is thus not an allergy. The autoantigen in coeliac disease is the tissue transglutaminase of the small intestine in the complex with the gluten ingested through food. Since only HLA molecules DQ2, DQ7 or DQ8 can bind to gluten and present it to the immune system, only carriers of these HLA types are affected by the disease. With a prevalence of 1:200–1:500, the disease is not uncommon.
Gluten from the ingestion of food (gliadin) is broken down by gastrointestinal enzymes. The resulting gliadin peptides pass through the mucous membrane of the small intestine, where they are deamidated by the tissue transglutaminase (tTg). In the complex, these deamidated gliadin peptides with the body's own tissue transglutaminase are absorbed by antigen-presenting macrophages of the intestinal wall and presented to the T lymphocytes. The gliadin-specific T helper cells activated as a result secrete cytokines (interleukin-2, interferon-γ, and tumour necrosis factor-α). These induce the expression of matrix metalloproteinases that are harmful to the mucosa, so causing damage directly to the mucous membrane (via apoptosis induction, for example). Activated B cells also produce antibodies against deamidated gliadin and tissue transglutaminase. These antibodies are detected in the laboratory diagnostics.
Patients suffer from chronic inflammation of the mucous membrane in the small intestine, villous atrophy, and crypt hypertrophy. The resulting clinical manifestations range from asymptomatic or mild through to severe forms. The patients with typical symptoms represent only the tip of the iceberg. Coeliac patients can develop the following symptoms:
|General||weight loss, tiredness, failure to thrive, anaemia|
|Gastrointestinal tract||bloated stomach, diarrhoea, nausea, stomach pain, vomiting|
|Muscular and skeletal systems||arthralgia, myalgia, osteoporosis, seizures|
|Skin and hair||oedema, dermatitis herpetiformis, alopecia|
|Oral cavity||aphthous stomatitis, enamel hypoplasia, burning tongue|
|Endocrine system||Infertility, repeated miscarriage|
Demonstrably, only the HLA molecules DQ2, DQ7, and DQ8 can present gliadin peptides. This means, for those who do not have one of the HLA types indicated, it is virtually impossible to develop coeliac disease. This makes the test for HLA-DQ2/DQ7/DQ8 very valuable for excluding coeliac disease.
Autoimmune diseases particularly are very closely associated with coeliac disease. If they occur together, coeliac disease is often asymptomatic:
Other diseases or symptom complexes:
As can be seen from the pathophysiology of coeliac disease, it is a genetically-determined T-cell-mediated chronic inflammatory autoimmune process that is directed against tissue of the small intestine. Diagnostic tests thus include serological, genetic and histological investigations.
Serological laboratory tests are very important. Highly sensitive serological antibody tests not only allow the diagnosis of coeliac disease, but can also be used for follow-up.
The following antibody tests are available:
Endomysial and transglutaminase IgA antibodies are very specific markers for the presence of coeliac disease and the combination of these two analyses ensures high sensitivity (~ 100%) and specificity (~ 100%) in the diagnosis of coeliac disease.
Testing for HLA-DQ2, DQ7 and DQ8 as alleles responsible for celiac disease predisposition is primarily carried out to identify risk patients and for exclusion of coeliac disease. This is possible because these HLA characteristics are an essential prerequisite for coeliac disease (99% of celiac disease patients carry one of the above HLA characteristics). It is almost impossible for patients, who do not carry these HLA characteristics, to develop coeliac disease. The determination of the HLA is not influenced by any diet.
The realisation that coeliac disease is the disease most closely associated with HLA led to new ESPGHAN (European Society of Paediatric Gastroenterology, Hepatology and Nutrition) guidelines in 2012 and new S2k guidelines from the German Society for Digestive and Metabolic Diseases in 2014. Both guidelines include the HLA test as a new diagnostic parameter. Regarding the recommended diagnostic algorithms, the guidelines distinguish between two patient groups:
In the case of patients with symptoms of coeliac disease, coeliac disease can be diagnosed without a biopsy if there is a positive result in the HLA test and the following prerequisites are fulfilled:
For patients with an increased risk of coeliac disease, due to the diseases above, and for first-degree relatives of coeliac patients, the diagnostics should begin with the HLA determination. This is because regularly repeated screening for antibodies is no longer necessary if there is a negative HLA result. If there is a positive HLA result, the transglutaminase IgA antibodies should be determined every two to three years.
Antibody testing: 5 ml serum (this is sufficient for several antibody tests)
HLA-genotyping: 2 ml EDTA blood
Transport of the blood sample to the laboratory is not time critical and can be done by mail. For genetic testing, we require the signed consent of the patient.For further questions please contact us by phone at 030 77001 220.