Coeliac disease

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. 

Pathogenesis of coeliac disease

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.

Image: Gliadin peptides in the complex with the body's own tissue transglutaminase are bound to the HLA molecules DQ2, DQ7, or DQ8 and activate gliadin-specific T-cells. The result is chronic inflammation of the intestinal mucosa.

The gluten-induced chronic inflammation of the mucous membrane in the small intestine causes varied clinical symptoms.

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:

Generalweight loss, tiredness, failure to thrive, anaemia
Gastrointestinal tractbloated stomach, diarrhoea, nausea, stomach pain, vomiting
Muscular and skeletal systemsarthralgia, myalgia, osteoporosis, seizures
Skin and hairoedema, dermatitis herpetiformis, alopecia
Oral cavityaphthous stomatitis, enamel hypoplasia, burning tongue
Endocrine systemInfertility, repeated miscarriage

Almost all coeliac patients (99.5%) carry one of the HLA types HLA-DQ2, DQ7, or DQ8.

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.

Certain diseases are up to ten times more common in patients with coeliac disease than in the normal population.

Autoimmune diseases particularly are very closely associated with coeliac disease. If they occur together, coeliac disease is often asymptomatic:

Autoimmune diseases:

  • Duhring's disease
  • Primary biliary cirrhosis
  • Psoriasis
  • Connective tissue diseases (Sjögren's syndrome; systemic lupus erythematosus)
  • Autoimmune hepatitis
  • Type 1 diabetes mellitus
  • Autoimmune thyroiditis
  • Addison's disease

Other diseases or symptom complexes:

  • Down’s or Turner syndrome
  • Crohn's disease
  • Ulcerative colitis
  • Osteoporosis
  • Migraine
  • Epilepsy
  • Irritable bowel syndrome
  • Depression and anxiety disorders
  • Bronchial asthma
  • Elevated transaminases
  • Selective IgA deficiency

Diagnosis of coeliac disease

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:

  • Anti-tissue transglutaminase antibodies IgG/IgA
  • Anti-endomysial antibodies IgG/IgA
  • Anti-deamidated gliadin antibodies IgG/IgA

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. 

Please keep in mind:

  • Up to 6% of coeliac patients have IgA deficiency.
    In these cases, the results of IgA antibodies are false negative and can therefore not be used for the assessment. To detect these, the total IgA should always be determined at the same time.
    In the case of known IgA deficiency, the respective IgG antibodies should be determined. Then, it is also recommended to test for endomysial and transglutaminase IgG antibodies as well as the IgG antibodies against deamidated gliadin.
  • Antibody titres go down with gluten free food.
    As such, serology tests (as well as the endoscopic examination) are of limited value  if carried out during a gluten-free diet. Therefore, a precise dietary history should be taken before blood collection.
  • A diagnosis can be made without a biopsy.  
    Up to now, if antibody tests were positive, it was recommended to confirm a diagnosis by means of a biopsy of the small intestine (histology). In accordance with the new S2k guidelines, coeliac disease can be diagnosed without a biopsy in some cases if, in addition to significantly positive serological results, one of the HLA types DQ2, DQ7, or DQ8 is present.

HLA typing for 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:

  1. Patients with symptoms of coeliac disease
  2. Asymptomatic coeliac at-risk patients

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:

  • Typical (gastrointestinal) manifestation
  • Transglutaminase IgA antibody titres elevated to 10 times more than the limit
  • Confirmation of seropositivity due to positive endomysial antibodies (≥ 1 : 5 IFT)
  • Clinical and serological remission under a gluten-free diet

Fig. 3: Diagnostic approach where there is a clinical suspicion of coeliac disease in line with the 2012 ESPGHAN criteria and the new 2014 S2k guideline.

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.

Fig. 4: Diagnostic approach in asymptomatic coeliac at-risk patients in line with the 2012 ESPGHAN guideline and the new 2014 S2k guideline.


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.


  • Brunner & Spalinger. Zöliakie im Kindesalter. Paediatrica  2005;16(3): 34.
  • Felber et al. 2014: S2k-Leitlinie Zöliakie, AWMF-Register-Nr. 021/021.
  • Kakinen et al. HLA-Typing in the diagnosis of Celiac Disease. Am J Gastroenterol 2002;97:695.
  • Husby et al. European Society for Pediatric Gasroenterology, Hepatology, and Nutrition guideline for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136.